Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)
Queen Mary University of London · Academic
In term In term in the September 2026 edition: the latest version runs to 28 February 2027.
- Reference
- DARS-NIC-245768-V0N2T
- Current version
- v2.7
- Term of current version
- 29 February 2024 to 28 February 2027
- Start date
- 1 March 2020
- Data controller
- Sole Data Controller
- Commercial purposes
- No
- Sublicensing
- No
- Files released to date
- 19
Why the data was released
Objective for processing
Queen Mary University of London requires access to NHS England data for the purpose of the following research programme: Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)
The following is a summary of the aims of the research programme provided by or on behalf of Queen Mary University of London:
1) To develop a prognostic model for progression after conservative treatment of prostate cancer using standard factors (Prostate Specific Antigen (PSA), Gleason grade, clinical stage).
2) To determine whether prediction of disease recurrence can be improved by the addition of other pathological, biological or molecular markers to the standard clinical factors.
Prostate cancer is the most common cancer affecting men in the UK with over 47,000 cases in 2015, representing over a quarter of all new cancer cases in males, and was the second leading cause of cancer death in 2015. Despite its rate of incidence and mortality, men are more likely to live with prostate cancer, as overall more than 85% of men diagnosed with prostate cancer will survive for ten or more years in England and Wales.
Localised prostate cancer in particular presents unique challenges in terms of differential diagnosis, and prognosis of aggressive versus indolent cancer and optimum treatment of clinically localised prostate cancer is poorly defined. Current inability to make the distinction poses the greatest problem when deciding appropriate clinical management strategies. This inability to biologically distinguish indolent from aggressive prostate cancer has led to over-diagnosis (identification of false positives) and overtreatment (treating false positives) of prostate cancer in cases where the cancers would not have caused clinical consequences. While only half of patients have potentially high-risk prostate cancer, up to 90% of patients with low-risk prostate cancer still undergo radical prostatectomy. It is known that cancer stage at diagnosis strongly influences the choice of treatment and anxiety also impacts on treatment decisions, with men opting for active treatment rather than active management. Overtreatment of low and intermediate risk prostate cancers is therefore a concern, especially in view of recent research which has shown there is no superiority of active treatment over active management in terms of survival.
Traditionally, standard clinical factors such as Prostate-Specific Antigen (PSA), Gleason Grade (GG) and clinical stage have been used to predict clinical tumour behaviour and stratify risk for progression. In particular, PSA testing is widely used as a screening tool for prostate cancer and to determine clinical management, despite its poor specificity and positive predictive value at borderline PSA values. Although PSA can be evaluated in conjunction with GG, tumour stage and other factors to produce the Cancer of the Prostate Risk Assessment (CAPRA), there remains significant heterogeneity in outcomes within these standard groupings and the aforementioned factors are not sufficiently discriminating.
Biomarkers have the potential to discriminate between low and high-risk localised prostate cancer. They play a significant role in oncology and are a means to better understand the molecular mechanisms behind tumour growth and progression. As defined by the National Institutes of Health Biomarkers Definitions Working Group, a biomarker “is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Biomarkers can be detected in blood, urine and tissue samples and can measure macro-molecules, such as DNA and RNA, cells and other biological processes.
Biomarkers are critical in the field of prostate cancer as they can determine diagnosis and prognosis, as well as recurrence and treatment response. Novel biological and pathological markers are urgently required in order to develop more accurate prognostic models that can be routinely used in the clinical setting. These models would significantly improve clinical management strategies and patients’ decisions on diagnosis with localised prostate cancer, avoiding interventions with significant morbidity and toxicity.
The Trans-Atlantic Prostate Group (TAPG) was established to examine the hypothesis that through a detailed retrospective analysis of outcome in a group of men with clinically localised prostate cancer at diagnosis, variables such as biological, pathological and clinical markers, could be identified that might accurately predict the prognosis of clinically localised prostate cancer.
In 1999, the TAPG group initiated the “Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting” study, referred to as the TAPG study. It is a retrospective population-based tissue sample study in men diagnosed with localised prostate cancer 1990-2006, inclusively. The study began as a collaboration between Queen Mary University of London (QMUL) and Sloan Kettering hospital in New York where most biomarkers analyses were performed. Hence the study was named as “Trans-Atlantic” (and the name shortened to “TAPG” for convenience), but the recruitment of prostate cancer patients came from the UK only. Initially the cohort comprised men diagnosed with prostate cancer with transurethral resection of the prostate (TURP) and needle biopsies 1990-1996, but was expanded in 2014 to include men diagnosed with prostate cancer 1990 – 2006. Data was collected from six regional cancer registries and eligibility was confirmed via hospital sites, which sent the relevant tissue samples to the TAPG Central Coordinating Office (CCO). Selection of eligible patients for the study completed in 2010. Since that year the TAPG CCO has been collecting cancer registration and mortality updates on the cohort members from regional cancer registries.
The Sloan Kettering Hospital is now no longer involved in this study. It was involved in the early stage of the biomarker analysis phase of the TAPG study, but this work is now being carried in its entirety at QMUL.
The CCO at the Centre for Cancer Prevention (CCP) at QMUL requires the continued collection of cancer and mortality data provided by NHS England. The data sets returned by NHS England will provide the TAPG CCO with vital information on prostate cancer progression. These data sets will be linked, via a study ID and personal identifiable data, to the participants' pathology data already collected from the hospital sites at which they were diagnosed, as well as clinical data already provided from the now dissolved regional cancer registries.
Although the study will not directly benefit patients diagnosed with prostate cancer after 2006, the assessment of the prognostic model will improve the decision-making process for men diagnosed with prostate cancer in the future. If implemented clinically, men diagnosed with prostate cancer will have a more accurate risk of progression and will be able to make an informed decision on treatment options available to them and whether or not to undergo radical therapy or embark on Active Surveillance. Lack of use of prognostic factors in routine clinical practice is currently a stumbling block to the over-diagnosis and over-treatment of prostate cancer. The prognostic factors under evaluation as part of this protocol could be integrated into the clinical setting in the future, as they are compatible and complementary to other clinical tests.
As stated in the 2014 NICE guidelines on ‘Prostate cancer: diagnosis and management’: “Further research is required into the identification of prognostic indicators in order to differentiate effectively between men who may die with prostate cancer and those who might die from prostate cancer. The greatest uncertainties in managing prostate cancer are around the identification of which cancers are of clinical significance and over the choice of radical treatment, and in which settings they are appropriate. With the diagnosis of prostate cancer being made more frequently in asymptomatic men, it is of growing importance to know which of these men are likely to benefit from aggressive treatment.”
https://www.nice.org.uk/guidance/cg175/resources/prostate-cancer-diagnosis-and-management-pdf-35109753913285
Therefore there remains an unmet need in terms of identification of prognostic indicators in differentiating aggressive and indolent cancers.
The following NHS England Data will be accessed:
Civil Registration Mortality, Cancer Registration and Demographics – necessary because the data sets returned by NHS England will provide the TAPG CCO with vital information on prostate cancer progression. The reports received from NHS England are essential in enabling the CCO to determine which pathological, clinical and biological markers can differentiate localised, indolent cancers from more aggressive cancers. The analyses will also enable the research community and patients to make more informed decisions on treatment pathways for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
The level of the Data will be:
• Identifiable – necessary because the data recipient can confirm the accuracy and strength of each linkage for TAPG participant in the study cohort. This ensures that all survival and cancer incidence data are correctly attributed to the each TAPG participant, thus avoiding any errors which would invalidate the study.
The Data will be minimised as follows:
• Limited to a study cohort identified by QMUL – the cohort provided is limited to men aged 18-76 years at the time of diagnosis. Inclusion criteria also states patients must have had a baseline serum PSA level measured before starting any prostate cancer specific treatment and within 6 months of diagnosis. Patients must have been diagnosed between 1990 and 2006 with clinically localized prostate cancer (clinical stage T1-T3, N0 or NX, M0 or MX) prostate cancer, in the judgement of treating physician. The cohort submitted consists of 3,500 individuals.
Queen Mary University of London is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.
The Barts Cancer Centre (BCC) is part of the Queen Mary University of London’s medical school; Barts and the London School of Medicine and Dentistry. The data received by NHS England which will be received by the Centre of Cancer Prevention (CCP) is a research unit which falls under the BCC. The BCC hosts a secure, walled of network within the QMUL environment so the legal entity/data controller here is QMUL but for processing data, this will be done under the BCC ‘safe haven’. Queen Mary University of London is therefore the sole controller.
The lawful basis for processing personal data under the UK GDPR is:
Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.
The lawful basis for processing special category data under the UK GDPR is:
Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.
The processing is in the public interest as it aims to improve the decision-making process for men diagnosed with prostate cancer.
There is no direct patient involvement as this is a retrospective study carried out in patients registered on UK regional cancer databases, as having prostate cancer diagnosed between 1990 and 2006 inclusively.
Processing activities
No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).
NHS England will provide the relevant records from the Cancer Registration, Civil Registrations of Deaths, and Demographics datasets to Queen Mary University of London. The Data will:
• contain directly identifying data items including Names, NHS Number, Date of Birth, Postcode, Gender which are required to confirm the accuracy and strength of each linkage for TAPG participant in the study cohort.
On receipt of the returned data set from NHS England, the CCP at QMUL will link this data set to the data set contained in the applicant's TAPG study database via the full name, date of birth, NHS number and study ID. As mentioned above, the data linkage enables the correct identification of the TAPG patients from the data set sent by NHS England.
Once the patients are identified, researchers at the CCP at QMUL will then update the participant entries in the TAPG study database with date and cause of death, prostate cancer progression, diagnosis and coding.
Following the linkage and participant identification, all identifiers except the study ID will be removed from the data set returned by NHS England and stored as a reference for analysis until study completion.
The Data will not be transferred to any other location.
The Data will be stored on servers at QMUL.
Queen Mary University of London uses offsite back-up services provided by Iron Mountain Ltd.
The Data will be accessed onsite at the premises of Queen Mary University of London only.
The Data will not leave England at any time.
Access is restricted to employees or agents of QMUL who have authorisation from the Chief Investigator.
All personnel accessing the Data have been appropriately trained in data protection and confidentiality.
The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.
Researchers from Queen Mary University of London will analyse the Data for the purposes described above.
Expected output
Further outputs and analyses of the TAPG study will be published in peer-reviewed journals, such as the Lancet, Journal of Clinical Oncology, or Cancer Research and Treatment, aimed at oncologists/clinicians, researchers and health professionals working within the prostate cancer field. In addition, the research team aims to present updated long-term follow-up data at national and international prostate cancer conferences.
The public will also be made aware of findings through appropriate channels, such as a Patient and Public Involvement event; One such event was hosted in January 2020 where participants were invited in to discuss research they have been a part of, to obtain their views and opinions as to how they feel about the research carried out so far, and also find out more about the current and future work carried out at the CCP. Publications with significant findings may be accompanied by press releases and subsequent news stories.
Publications, conference attendance and results are published regularly and are available on www.qmul.ac.uk/wolfson. There is also a public Twitter account where updates will be posted on. (https://twitter.com/qmccp).
Expected measurable benefits
The TAPG study is the largest and most comprehensive study of long-term cause-specific mortality in men managed for prostate cancer by Active Surveillance.
The TAPG study is focused on understanding prognosis of early prostate cancer managed by Active Surveillance. There have been more than 30 scientific papers published, but the most influential has been the PROLARIS cell cycle progression score ( Cuzick et al 2011; 2012), which can help to determine which patients with early disease can be safely managed by Active Surveillance and which need more aggressive radical treatment. It is currently the most widely used prognostic test in the United States and has a major impact on patient management, therefore this research enables it to be applied in the UK to benefit the UK health and care system.
The datasets returned by NHS England will provide vital information on the pathological, clinical and biological markers and how they can differentiate localised, indolent cancers from more aggressive cancers. Upon receipt of the mortality data from NHS England, the research team will link this information with the biomarker data from the tissue block analysis to assess further the predictive value of biomarkers in relation to disease progression and death from prostate cancer. The analyses will also enable the research community and patients to make more informed decisions on treatment pathways for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment. The main objective for obtaining data from NHS England is to understand the long-term risk/benefit.
One of the strongest biomarkers found to date was a cell cycle progression panel based on RNA expression of 31 genes (Cuzick et all, 2011). It has been widely used around the world, especially in the United States, and is currently being evaluated for cost effectiveness in the UK by the National Institute for Health and Care Excellence (NICE). Although the current results from the various biomarker and outcome analyses do not benefit the TAPG cohort per se, the discovery of predictive markers for prostate cancer death and its implementation in the UK Health system will benefit many patients with prostate cancer.
There are many papers in consideration at the moment using data collected for the TAPG study. Some of these are; a comparison of CCP and Ki-67 score, looking at how well cribriform patterns predict prostate cancer death, follow-up on men who were biopsied with needle, methodological methods on time varying covariates/time varying risk scores using TAPG data, how well different clinical scores and clinical variables predict prostate cancer death in different time periods and looking at cancer extent on prostate cancer deaths. The latter is going through revisions to answer reviewer’s comments. All these new papers will broaden the preventive scope for the future of prostate cancer. Continuing to obtain the long term follow up data via NHS England is pivotal in the success of these papers and allows further speculation.
Continuing to obtain the long term follow up data via NHS England is pivotal in the success of these papers and allows further speculation. The data would allow for the update of the Myriad Prolaris report; this would provide immediate benefit because it would provide evidence of long-term safety and durability. With this expanded evidence, insurance providers may also choose to cover Prolaris testing for more individuals.
There is no current valid estimate for 15-year follow-up; this data would provide immediate benefit for that timeframe. In addition the Prolaris validation cohorts are based on a UK patient population so this data would further align/support this population. The research team predicts a one year timeframe for recognising this benefit.
Benefits reported so far
YIELDED BENEFITS ACHIEVED PRIOR TO RECEIVING ANY NHS ENGLAND DATA
The use of the previously collected Registry data has allowed the research team to identify numerous cases of prostate cancer, which are a part of the TAPG cohort. Collection and processing of data from previous TAPG research has contributed directly to the primary endpoint of the trial (death from prostate cancer) and will continue to provide valuable information on understanding the pathological features of prostate cancer. It was also a useful aid in determining if the prediction of disease recurrence could be improved by the addition of other pathological, biological or molecular markers to the standard clinical factors. The data sets previously received have also helped with observing long term outcomes in men that are on Active Surveillance, thus getting a better understanding of the disease.
The Transatlantic Prostate Group has demonstrated the prognostic value of pathological, biological and molecular markers, as evidenced by the numerous publications from 2006 to present.
1) Clinical
First analysis of the first cohort of patients diagnosed with localised prostate cancer (n=2,333) from 1990 to 1996, after a 12-year median follow-up period, focussed on traditional clinical markers: Gleason Grade, serum PSA, clinical stage, as well as cancer extent in biopsy (Cuzick et al (2006)). The analysis demonstrated that Gleason score was an important determinant of cancer-specific mortality. PSA level, clinical stage and extent of disease also had predictive value. However, the study highlighted that long-term follow-up of men was necessary as it was not clear whether mortality rate trends plateau or continue to increase 15-20 years following diagnosis. Furthermore, the analysis identified that men in the cohort with an intermediate prognosis require better markers of disease progression, in order to assist in formulating appropriate management of individual men with prostate cancer.
2) Histopathological
Histo-pathological analyses of clinical markers have also generated findings of relevance to the disease area. In 2007 Berney et al examined the diagnostic accuracy and concordance with which diagnostic pathologists in the UK applied Gleason grading criteria, together with the likely consequences of the grades assigned to patient management. The objective was to test the hypothesis that the study would reveal a previous broad interpretation of Gleason grading criteria which, when applied to a large group of untreated prostate cancers and standardized according to conventional and internationally agreed criteria, would be a powerful predictor of prognosis. The study demonstrated that there was a significant error rate both in cancer diagnosis and in Gleason grading, with a significant upgrading in most biopsy and TURP specimens: 7.5% of the examined cases were reassigned to a non-malignant diagnosis. The effect of grade reassignment on the diagnosis and management of prostate cancer is considerable. Very few studies have examined the rate of misdiagnosis in prostatic cancer retrospectively, and none in such a large series as that now reported. The study highlighted that over-diagnosis of prostatic cancer is likely to have numerous consequences if the findings of this study are reflected internationally. From an individual patient’s point of view, the consequences are those of unnecessary distress, psychological impact and the significant risks of over-treatment, including hormonal therapy, radiotherapy or even radical prostatectomy.
3) Genetic
The Trans-Atlantic Prostate Group has produced analyses reporting the clinical significance of various genetic markers. In 2008 Attard et al reported CI5orf21 as novel fusion partner for ETV1, and the heterogeneity of ETV1 gene arrangements in human prostate cancer. In a separate publication in the same year, Attard et al also identified a novel category of prostate cancers characterised by duplication of the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of 2+Edel. The authors concluded that the aforementioned genetic sequences could be part of a new mechanism-based prognostic classification for assessing the potential future aggressiveness of every human prostate cancer at diagnosis.
4) Prognostic models & scores
With regards to prognostic models, the Trans-Atlantic Prostate Group has developed various models and scores for the prediction of progression of prostate cancer and disease-specific survival. In 2008, Kattan et al developed and internally validated the first nomogram for prediction of disease-specific survival, since outcome prediction models for watchful waiting are rare relative to those available for aggressive therapies such as surgery or radiation therapy. The nomogram predicted well with a concordance index of 0.73 and had good calibration. This is an accurate tool for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counselling and clinical trial design.
There have been several papers such as Histopathologic False-positive Diagnosis of Prostate Cancer in the Age of Immunohistochemistry - The American Journal of Surgical Pathology 2018 and Validation of the cell cycle progression score to differentiate indolent from aggressive prostate cancer in men diagnosed through transurethral resection of the prostate biopsy - Cancer Reports 2021. All data collection via NHS England for the TAPG cohort contributes to the future of preventive measures and approaches to reducing the long term undesirable outcomes currently experienced for men with a prostate cancer diagnosis.
There are currently no identified further yielded benefits at this time QMUL continue to monitor the continued follow-up data for this purpose.
Datasets on the current version
Legal basis for provision: Health and Social Care Act 2012 - s261(5)(d)
| Dataset | Type of data | Sensitivity | Frequency | Confidential data |
|---|---|---|---|---|
| Cancer Registration Data | Identifiable | Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Civil Registrations of Death | Identifiable | Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Demographics | Identifiable | Sensitive | Ongoing | Section 251 NHS Act 2006 |
Files released
Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.
Patient opt-outs were applied to all 19 files released under this agreement, across every version. About opt-outs
Files released against version 2.7 of this agreement, summarised by dataset.
| Dataset | Files | First released | Last released | Opt-outs applied |
|---|---|---|---|---|
| Demographics | 4 | March 2024 | March 2026 | Yes |
| Cancer Registration Data | 3 | March 2024 | March 2026 | Yes |
| Civil Registrations of Death | 3 | March 2024 | March 2026 | Yes |
Version history
The register lists each renewal of this agreement as a separate row. This site has 3 versions.
DARS-NIC-245768-V0N2T-v2.7 29 February 2024 to 28 February 2027
- Title
- Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 3
- Files released
- 10
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics
What changed from DARS-NIC-245768-V0N2T-v1.4
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2024-02-29 | |
| End date | 2027-02-28 | |
| Cancer Registration Data: legal basis | Health and Social Care Act 2012 - s261(5)(d) | |
| Civil Registrations of Death: legal basis | Health and Social Care Act 2012 - s261(5)(d) | |
| Demographics: legal basis | Health and Social Care Act 2012 - s261(5)(d) |
Objective for processing
Queen Mary University of London requires access to NHS England data for the purpose of the following research programme: Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)
The following is a summary of the aims of the research programme provided by or on behalf of Queen Mary University of London:
1) To develop a prognostic model for progression after conservative treatment of prostate cancer using standard factors (Prostate Specific Antigen (PSA), Gleason grade, clinical stage).
2) To determine whether prediction of disease recurrence can be improved by the addition of other pathological, biological or molecular markers to the standard clinical factors.
[9 paragraphs unchanged]
The reports received from NHS England are essential in enabling the CCO to determine which pathological, clinical and biological markers can differentiate localised, indolent cancers from more aggressive cancers. The analyses will also enable the research community and patients to make more informed decisions on treatment pathways for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
[4 paragraphs unchanged]
The following NHS England Data will be accessed:
Civil Registration Mortality, Cancer Registration and Demographics – necessary because the data sets returned by NHS England will provide the TAPG CCO with vital information on prostate cancer progression. The reports received from NHS England are essential in enabling the CCO to determine which pathological, clinical and biological markers can differentiate localised, indolent cancers from more aggressive cancers. The analyses will also enable the research community and patients to make more informed decisions on treatment pathways for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
The level of the Data will be:
• Identifiable – necessary because the data recipient can confirm the accuracy and strength of each linkage for TAPG participant in the study cohort. This ensures that all survival and cancer incidence data are correctly attributed to the each TAPG participant, thus avoiding any errors which would invalidate the study.
The Data will be minimised as follows:
• Limited to a study cohort identified by QMUL – the cohort provided is limited to men aged 18-76 years at the time of diagnosis. Inclusion criteria also states patients must have had a baseline serum PSA level measured before starting any prostate cancer specific treatment and within 6 months of diagnosis. Patients must have been diagnosed between 1990 and 2006 with clinically localized prostate cancer (clinical stage T1-T3, N0 or NX, M0 or MX) prostate cancer, in the judgement of treating physician. The cohort submitted consists of 3,500 individuals.
Queen Mary University of London is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.
[1 paragraph unchanged]
The legal basis for processing this data is Article 6(1)(e) ‘performance of a task carried out in the public interest’ pursuant to the GDPR. As the research involves the use of health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing, namely article 9 (2) j which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards.
The lawful basis for processing personal data under the UK GDPR is:
Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.
The lawful basis for processing special category data under the UK GDPR is:
Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.
[1 paragraph unchanged]
This study has Health Research Authority (HRA) Confidentiality Advisory Group (CAG) ‘Section 251 support’ (CAG reference: ECC 3-06(m)/2009), which permits the processing of confidential patient information without consent and HRA Ethics approval (REC Ref. 99/3/040).
There is no direct patient involvement as this is a retrospective study carried out in patients registered on UK regional cancer databases, as having prostate cancer diagnosed between 1990 and 2006 inclusively.
Processing activities
The Centre for Cancer Prevention (CCP) at QMUL will send a TAPG cohort data, i.e. a list of TAPG study participants, to NHS England for linkage. The cohort to be submitted is 3,500 individuals. The following identifiers will be sent to NHS England by the CCP team at QMUL:
No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).
-Full Name,
NHS England will provide the relevant records from the Cancer Registration, Civil Registrations of Deaths, and Demographics datasets to Queen Mary University of London. The Data will:
-Date Of Birth,
• contain directly identifying data items including Names, NHS Number, Date of Birth, Postcode, Gender which are required to confirm the accuracy and strength of each linkage for TAPG participant in the study cohort.
-NHS Number,
-Study ID
-Hospital ID
-Previous Cancer registry ID
-Date of death (if required)
-Post code.
For Data Minimisation purposes, the cohort to be provided is limited to men aged 18-76 years at the time of diagnosis. Inclusion criteria also states patients must have had a baseline serum PSA level measured before starting any prostate cancer specific treatment and within 6 months of diagnosis. Patients must have been diagnosed between 1990 and 2006 with clinically localized prostate cancer (clinical stage T1-T3, N0 or NX, M0 or MX) prostate cancer, in the judgement of treating physician.
There is no direct patient involvement as this is a retrospective study carried out in patients registered on UK regional cancer databases, as having prostate cancer diagnosed between 1990 and 2006 inclusively.
The data received by the CCP at QMUL will not be used for any purpose other than to meet objectives as stated in the trial protocol and will not be shared with any other third party or organisation.
The data sets returned by NHS England to the CCP team at QMUL will contain identifiable data. This is so that the applicant can confirm the accuracy and strength of each linkage for TAPG participant in the study cohort. This ensures that all survival and cancer incidence data are correctly attributed to the each TAPG participant, thus avoiding any errors which would invalidate the study.
[3 paragraphs unchanged]
Processed data sets with all identifiers removed except the study ID will be retained for analysis until study completion, following which it will be archived for 20 years. The original data set returned by NHS England containing identifiable data will be stored on a separate server meeting NHS England security requirements, as per DARS Guidance Notes on Security for where Mortality data is involved.
The Data will not be transferred to any other location.
The applicant would like to emphasise that personal identifiable data are stored on the secure network and never on the local drives of unencrypted QMUL desktop PCs.
The Data will be stored on servers at QMUL.
Bart's Cancer Centre IT Network creates back-ups of the data stored on its network. The encrypted backup tapes are stored offsite with Iron Mountain UK Ltd. The data is not accessible by any Iron Mountain employee.
Queen Mary University of London uses offsite back-up services provided by Iron Mountain Ltd.
All personal identifiable data received at the Centre for Cancer Prevention are stored electronically on an Oracle database, local to and administered by substantive employees of QMUL only. Personal identifiers of study participants are encrypted in the Oracle database and stored separately to the clinical data, with access strictly restricted to only QMUL substantive members of staff who have accredited researcher status. Only these members of staff will have access to the personal identifiable data. Additionally, access to the personal identifiers on the Oracle database is controlled by separate username and password access and is controlled by the IT Department.
The Data will be accessed onsite at the premises of Queen Mary University of London only.
Staff that are delegated duties such as data entry/cleaning and manipulation are required to undergo an ONS (Office for National Statistics) accredited researcher training to access and view patient identifiable data sets. This training course covers a variety of topics including data security. Upon completion of training and achieving a pass in the test, an accreditation number is provided and this allows the individual to access such data. Accredited researcher training is mandatory to view such data. Staff are strongly advised to complete an information governance training course and upon completion and passing the test, a certificate is provided.
The Data will not leave England at any time.
The separate mortality and HES servers are self-contained within the Bart’s Cancer Centre IT network, within the QMUL network. They are firewalled from external connections and the rest of the network. All traffic through the checkpoint firewall is logged.
Access is restricted to employees or agents of QMUL who have authorisation from the Chief Investigator.
Data will be accessed within the network using workstations that have a currently supported operating system which includes security patches. No remote access (i.e. through a VPN/RDP connection) is permitted. No mobile devices will be used to access any data. The network is externally scanned on a regular basis.
All personnel accessing the Data have been appropriately trained in data protection and confidentiality.
The data sets from NHS England will be stored until the data destruction date as per this agreement with NHS England. The storage architecture is compliant with the NHS England Data Sharing Framework Contract and once QMUL is issued with a Data Destruction notice, the data from all storage including backups can be securely and permanently removed within 14 days. Data can be securely wiped to NHS England standards (multi-pass pattern wiped to at least HMG S5 Enhanced on site and if end of life, degaussed and physically destroyed).
The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.
Researchers from Queen Mary University of London will analyse the Data for the purposes described above.
Expected measurable benefits
[2 paragraphs unchanged] The datasets returned by NHS England will provide vital information on the [78 words unchanged] for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment. The main objective for obtaining data from NHS England is to understand the long-term risk/benefit. [2 paragraphs unchanged] Continuing to obtain the long term follow up data via NHS England is pivotal in the success of these papers and allows further speculation. The data would allow for the update of the Myriad Prolaris report; this would provide immediate benefit because it would provide evidence of long-term safety and durability. With this expanded evidence, insurance providers may also choose to cover Prolaris testing for more individuals. There is no current valid estimate for 15-year follow-up; this data would provide immediate benefit for that timeframe. In addition the Prolaris validation cohorts are based on a UK patient population so this data would further align/support this population. The research team predicts a one year timeframe for recognising this benefit.
Benefits reported
[12 paragraphs unchanged] There are currently no identified further yielded benefits at this time QMUL continue to monitor the continued follow-up data for this purpose.
Unchanged: Expected output.
DARS-NIC-245768-V0N2T-v1.4 26 June 2023 to 28 February 2024
- Title
- Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 3
- Files released
- 0
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics
What changed from DARS-NIC-245768-V0N2T-v0.6
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Title | Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG) | |
| Start date | 2023-06-26 | |
| End date | 2024-02-28 | |
| Cancer Registration Data: legal basis | Health and Social Care Act 2012 - s261(5)(d); National Health Service Act 2006 - s251 - 'Control of patient information'. | |
| Civil Registrations of Death: legal basis | Health and Social Care Act 2012 - s261(5)(d); National Health Service Act 2006 - s251 - 'Control of patient information'. | |
| Demographics: legal basis | Health and Social Care Act 2012 - s261(5)(d); National Health Service Act 2006 - s251 - 'Control of patient information'. |
Objective for processing
[8 paragraphs unchanged]
The CCO at the Centre for Cancer Prevention (CCP) at
Queen Mary University London (QMUL) seeks to continue to collect
QMUL requires the continued collection of
cancer and mortality data provided by NHS
Digital. seeks to continue to collect cancer and mortality data via data provided by NHS Digital.
England.
The data sets returned by NHS
Digital
England
will provide the TAPG CCO with vital information on prostate cancer progression.
[32 words unchanged]
as clinical data already provided from the now dissolved regional cancer registries.
The reports received from NHS
Digital
England
are essential in enabling the CCO to determine which pathological, clinical and
[29 words unchanged]
for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
[4 paragraphs unchanged]
The legal bases for processing this data is Article 6(1)(e) ‘performance of a task carried out in the public interest’ pursuant to the GDPR. As the research involves the use of health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing, namely article 9 (2) j which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards. This study has Health Research Authority (HRA) Confidentiality Advisory Group (CAG) ‘Section 251 support’ (CAG reference: ECC 3-06(m)/2009), which permits the processing of confidential patient information without consent and HRA Ethics approval (REC Ref. 99/3/040).
The Barts Cancer Centre (BCC) is part of the Queen Mary University of London’s medical school; Barts and the London School of Medicine and Dentistry. The data received by NHS England which will be received by the Centre of Cancer Prevention (CCP) is a research unit which falls under the BCC. The BCC hosts a secure, walled of network within the QMUL environment so the legal entity/data controller here is QMUL but for processing data, this will be done under the BCC ‘safe haven’. Queen Mary University of London is therefore the sole controller.
The legal basis for processing this data is Article 6(1)(e) ‘performance of a task carried out in the public interest’ pursuant to the GDPR. As the research involves the use of health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing, namely article 9 (2) j which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards.
The processing is in the public interest as it aims to improve the decision-making process for men diagnosed with prostate cancer.
This study has Health Research Authority (HRA) Confidentiality Advisory Group (CAG) ‘Section 251 support’ (CAG reference: ECC 3-06(m)/2009), which permits the processing of confidential patient information without consent and HRA Ethics approval (REC Ref. 99/3/040).
Processing activities
All organisations party to this agreement must comply with the Data Sharing Framework Contract, including requirements on the use (and purposes of that use) by "Personnel" (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).
The Centre for Cancer Prevention (CCP) at QMUL will send a TAPG cohort data, i.e. a list of TAPG study participants, to NHS England for linkage. The cohort to be submitted is 3,500 individuals. The following identifiers will be sent to NHS England by the CCP team at QMUL:
The Barts Cancer Centre (BCC) is part of the Queen Mary University of London’s medical school; Barts and the London School of Medicine and Dentistry. The data received by NHS Digital which will be received by the Centre of Cancer Prevention (CCP) is a research unit which falls under the BCC. The BCC hosts a secure, walled of network within the QMUL environment so the legal entity/data controller here is QMUL but for processing data, this will be done under the BCC ‘safe haven’. Queen Mary University of London is therefore the sole data controller.
The Centre for Cancer Prevention (CCP) at QMUL will send a TAPG cohort data, i.e. a list of TAPG study participants, to NHS Digital for linkage. The cohort to be submitted is 3,500 individuals. The following identifiers will be sent to NHS Digital by the CCP team at QMUL:
[11 paragraphs unchanged]
The data sets returned by NHS
Digital
England
to the CCP team at QMUL will contain identifiable data. This is
[34 words unchanged]
each TAPG participant, thus avoiding any errors which would invalidate the study.
On receipt of the returned data set from NHS
Digital,
England,
the CCP at QMUL will link this data set to the data
[29 words unchanged]
identification of the TAPG patients from the data set sent by NHS
Digital.
England.
[1 paragraph unchanged]
Following the linkage and participant identification, all identifiers except the study ID will be removed from the data set returned by NHS
Digital
England
and stored as a reference for analysis until study completion.
Processed data sets with all identifiers removed except the study ID will
[11 words unchanged]
be archived for 20 years. The original data set returned by NHS
Digital
England
containing identifiable data will be stored on a separate server meeting NHS
Digital
England
security requirements, as per DARS Guidance Notes on Security for where Mortality data is involved.
[6 paragraphs unchanged]
The data sets from NHS
Digital
England
will be stored until the data destruction date as per this agreement with NHS
Digital.
England.
The storage architecture is compliant with the NHS
Digital
England
Data Sharing Framework Contract and once QMUL is issued with a Data
[13 words unchanged]
permanently removed within 14 days. Data can be securely wiped to NHS
Digital
England
standards (multi-pass pattern wiped to at least HMG S5 Enhanced on site and if end of life, degaussed and physically destroyed).
Expected measurable benefits
[2 paragraphs unchanged]
The datasets returned by NHS
Digital
England
will provide vital information on the pathological, clinical and biological markers and
[7 words unchanged]
from more aggressive cancers. Upon receipt of the mortality data from NHS
Digital,
England,
the research team will link this information with the biomarker data from
[40 words unchanged]
for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
[1 paragraph unchanged]
There are many papers in consideration at the moment using data collected for the TAPG study. Some of these are; a comparison of CCP and Ki-67 score, looking at how well cribriform patterns predict prostate cancer death, follow-up on men who were biopsied with needle, methodological methods on time varying covariates/time varying risk scores using TAPG data, how well different clinical scores and clinical variables predict prostate cancer death in different time periods and looking at cancer extent on prostate cancer deaths. The latter is going through revisions to answer reviewer’s comments. All these new papers will broaden the preventive scope for the future of prostate cancer. Continuing to obtain the long term follow up data via NHS England is pivotal in the success of these papers and allows further speculation.
Benefits reported
YIELDED BENEFITS ACHIEVED PRIOR TO RECEIVING ANY NHS
DIGITAL
ENGLAND
DATA
[10 paragraphs unchanged]
[The full account of studies completed and the list of bibliographies can be found in Supporting Document SD13]
There have been several papers such as Histopathologic False-positive Diagnosis of Prostate Cancer in the Age of Immunohistochemistry - The American Journal of Surgical Pathology 2018 and Validation of the cell cycle progression score to differentiate indolent from aggressive prostate cancer in men diagnosed through transurethral resection of the prostate biopsy - Cancer Reports 2021. All data collection via NHS England for the TAPG cohort contributes to the future of preventive measures and approaches to reducing the long term undesirable outcomes currently experienced for men with a prostate cancer diagnosis.
Unchanged: Expected output.
Objective for processing
Prostate cancer is the most common cancer affecting men in the UK with over 47,000 cases in 2015, representing over a quarter of all new cancer cases in males, and was the second leading cause of cancer death in 2015. Despite its rate of incidence and mortality, men are more likely to live with prostate cancer, as overall more than 85% of men diagnosed with prostate cancer will survive for ten or more years in England and Wales.
Localised prostate cancer in particular presents unique challenges in terms of differential diagnosis, and prognosis of aggressive versus indolent cancer and optimum treatment of clinically localised prostate cancer is poorly defined. Current inability to make the distinction poses the greatest problem when deciding appropriate clinical management strategies. This inability to biologically distinguish indolent from aggressive prostate cancer has led to over-diagnosis (identification of false positives) and overtreatment (treating false positives) of prostate cancer in cases where the cancers would not have caused clinical consequences. While only half of patients have potentially high-risk prostate cancer, up to 90% of patients with low-risk prostate cancer still undergo radical prostatectomy. It is known that cancer stage at diagnosis strongly influences the choice of treatment and anxiety also impacts on treatment decisions, with men opting for active treatment rather than active management. Overtreatment of low and intermediate risk prostate cancers is therefore a concern, especially in view of recent research which has shown there is no superiority of active treatment over active management in terms of survival.
Traditionally, standard clinical factors such as Prostate-Specific Antigen (PSA), Gleason Grade (GG) and clinical stage have been used to predict clinical tumour behaviour and stratify risk for progression. In particular, PSA testing is widely used as a screening tool for prostate cancer and to determine clinical management, despite its poor specificity and positive predictive value at borderline PSA values. Although PSA can be evaluated in conjunction with GG, tumour stage and other factors to produce the Cancer of the Prostate Risk Assessment (CAPRA), there remains significant heterogeneity in outcomes within these standard groupings and the aforementioned factors are not sufficiently discriminating.
Biomarkers have the potential to discriminate between low and high-risk localised prostate cancer. They play a significant role in oncology and are a means to better understand the molecular mechanisms behind tumour growth and progression. As defined by the National Institutes of Health Biomarkers Definitions Working Group, a biomarker “is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Biomarkers can be detected in blood, urine and tissue samples and can measure macro-molecules, such as DNA and RNA, cells and other biological processes.
Biomarkers are critical in the field of prostate cancer as they can determine diagnosis and prognosis, as well as recurrence and treatment response. Novel biological and pathological markers are urgently required in order to develop more accurate prognostic models that can be routinely used in the clinical setting. These models would significantly improve clinical management strategies and patients’ decisions on diagnosis with localised prostate cancer, avoiding interventions with significant morbidity and toxicity.
The Trans-Atlantic Prostate Group (TAPG) was established to examine the hypothesis that through a detailed retrospective analysis of outcome in a group of men with clinically localised prostate cancer at diagnosis, variables such as biological, pathological and clinical markers, could be identified that might accurately predict the prognosis of clinically localised prostate cancer.
In 1999, the TAPG group initiated the “Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting” study, referred to as the TAPG study. It is a retrospective population-based tissue sample study in men diagnosed with localised prostate cancer 1990-2006, inclusively. The study began as a collaboration between Queen Mary University of London (QMUL) and Sloan Kettering hospital in New York where most biomarkers analyses were performed. Hence the study was named as “Trans-Atlantic” (and the name shortened to “TAPG” for convenience), but the recruitment of prostate cancer patients came from the UK only. Initially the cohort comprised men diagnosed with prostate cancer with transurethral resection of the prostate (TURP) and needle biopsies 1990-1996, but was expanded in 2014 to include men diagnosed with prostate cancer 1990 – 2006. Data was collected from six regional cancer registries and eligibility was confirmed via hospital sites, which sent the relevant tissue samples to the TAPG Central Coordinating Office (CCO). Selection of eligible patients for the study completed in 2010. Since that year the TAPG CCO has been collecting cancer registration and mortality updates on the cohort members from regional cancer registries.
The Sloan Kettering Hospital is now no longer involved in this study. It was involved in the early stage of the biomarker analysis phase of the TAPG study, but this work is now being carried in its entirety at QMUL.
The CCO at the Centre for Cancer Prevention (CCP) at QMUL requires the continued collection of cancer and mortality data provided by NHS England. The data sets returned by NHS England will provide the TAPG CCO with vital information on prostate cancer progression. These data sets will be linked, via a study ID and personal identifiable data, to the participants' pathology data already collected from the hospital sites at which they were diagnosed, as well as clinical data already provided from the now dissolved regional cancer registries.
The reports received from NHS England are essential in enabling the CCO to determine which pathological, clinical and biological markers can differentiate localised, indolent cancers from more aggressive cancers. The analyses will also enable the research community and patients to make more informed decisions on treatment pathways for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
Although the study will not directly benefit patients diagnosed with prostate cancer after 2006, the assessment of the prognostic model will improve the decision-making process for men diagnosed with prostate cancer in the future. If implemented clinically, men diagnosed with prostate cancer will have a more accurate risk of progression and will be able to make an informed decision on treatment options available to them and whether or not to undergo radical therapy or embark on Active Surveillance. Lack of use of prognostic factors in routine clinical practice is currently a stumbling block to the over-diagnosis and over-treatment of prostate cancer. The prognostic factors under evaluation as part of this protocol could be integrated into the clinical setting in the future, as they are compatible and complementary to other clinical tests.
As stated in the 2014 NICE guidelines on ‘Prostate cancer: diagnosis and management’: “Further research is required into the identification of prognostic indicators in order to differentiate effectively between men who may die with prostate cancer and those who might die from prostate cancer. The greatest uncertainties in managing prostate cancer are around the identification of which cancers are of clinical significance and over the choice of radical treatment, and in which settings they are appropriate. With the diagnosis of prostate cancer being made more frequently in asymptomatic men, it is of growing importance to know which of these men are likely to benefit from aggressive treatment.”
https://www.nice.org.uk/guidance/cg175/resources/prostate-cancer-diagnosis-and-management-pdf-35109753913285
Therefore there remains an unmet need in terms of identification of prognostic indicators in differentiating aggressive and indolent cancers.
The Barts Cancer Centre (BCC) is part of the Queen Mary University of London’s medical school; Barts and the London School of Medicine and Dentistry. The data received by NHS England which will be received by the Centre of Cancer Prevention (CCP) is a research unit which falls under the BCC. The BCC hosts a secure, walled of network within the QMUL environment so the legal entity/data controller here is QMUL but for processing data, this will be done under the BCC ‘safe haven’. Queen Mary University of London is therefore the sole controller.
The legal basis for processing this data is Article 6(1)(e) ‘performance of a task carried out in the public interest’ pursuant to the GDPR. As the research involves the use of health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing, namely article 9 (2) j which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards.
The processing is in the public interest as it aims to improve the decision-making process for men diagnosed with prostate cancer.
This study has Health Research Authority (HRA) Confidentiality Advisory Group (CAG) ‘Section 251 support’ (CAG reference: ECC 3-06(m)/2009), which permits the processing of confidential patient information without consent and HRA Ethics approval (REC Ref. 99/3/040).
Expected output
Further outputs and analyses of the TAPG study will be published in peer-reviewed journals, such as the Lancet, Journal of Clinical Oncology, or Cancer Research and Treatment, aimed at oncologists/clinicians, researchers and health professionals working within the prostate cancer field. In addition, the research team aims to present updated long-term follow-up data at national and international prostate cancer conferences.
The public will also be made aware of findings through appropriate channels, such as a Patient and Public Involvement event; One such event was hosted in January 2020 where participants were invited in to discuss research they have been a part of, to obtain their views and opinions as to how they feel about the research carried out so far, and also find out more about the current and future work carried out at the CCP. Publications with significant findings may be accompanied by press releases and subsequent news stories.
Publications, conference attendance and results are published regularly and are available on www.qmul.ac.uk/wolfson. There is also a public Twitter account where updates will be posted on. (https://twitter.com/qmccp).
Benefits reported
YIELDED BENEFITS ACHIEVED PRIOR TO RECEIVING ANY NHS ENGLAND DATA
The use of the previously collected Registry data has allowed the research team to identify numerous cases of prostate cancer, which are a part of the TAPG cohort. Collection and processing of data from previous TAPG research has contributed directly to the primary endpoint of the trial (death from prostate cancer) and will continue to provide valuable information on understanding the pathological features of prostate cancer. It was also a useful aid in determining if the prediction of disease recurrence could be improved by the addition of other pathological, biological or molecular markers to the standard clinical factors. The data sets previously received have also helped with observing long term outcomes in men that are on Active Surveillance, thus getting a better understanding of the disease.
The Transatlantic Prostate Group has demonstrated the prognostic value of pathological, biological and molecular markers, as evidenced by the numerous publications from 2006 to present.
1) Clinical
First analysis of the first cohort of patients diagnosed with localised prostate cancer (n=2,333) from 1990 to 1996, after a 12-year median follow-up period, focussed on traditional clinical markers: Gleason Grade, serum PSA, clinical stage, as well as cancer extent in biopsy (Cuzick et al (2006)). The analysis demonstrated that Gleason score was an important determinant of cancer-specific mortality. PSA level, clinical stage and extent of disease also had predictive value. However, the study highlighted that long-term follow-up of men was necessary as it was not clear whether mortality rate trends plateau or continue to increase 15-20 years following diagnosis. Furthermore, the analysis identified that men in the cohort with an intermediate prognosis require better markers of disease progression, in order to assist in formulating appropriate management of individual men with prostate cancer.
2) Histopathological
Histo-pathological analyses of clinical markers have also generated findings of relevance to the disease area. In 2007 Berney et al examined the diagnostic accuracy and concordance with which diagnostic pathologists in the UK applied Gleason grading criteria, together with the likely consequences of the grades assigned to patient management. The objective was to test the hypothesis that the study would reveal a previous broad interpretation of Gleason grading criteria which, when applied to a large group of untreated prostate cancers and standardized according to conventional and internationally agreed criteria, would be a powerful predictor of prognosis. The study demonstrated that there was a significant error rate both in cancer diagnosis and in Gleason grading, with a significant upgrading in most biopsy and TURP specimens: 7.5% of the examined cases were reassigned to a non-malignant diagnosis. The effect of grade reassignment on the diagnosis and management of prostate cancer is considerable. Very few studies have examined the rate of misdiagnosis in prostatic cancer retrospectively, and none in such a large series as that now reported. The study highlighted that over-diagnosis of prostatic cancer is likely to have numerous consequences if the findings of this study are reflected internationally. From an individual patient’s point of view, the consequences are those of unnecessary distress, psychological impact and the significant risks of over-treatment, including hormonal therapy, radiotherapy or even radical prostatectomy.
3) Genetic
The Trans-Atlantic Prostate Group has produced analyses reporting the clinical significance of various genetic markers. In 2008 Attard et al reported CI5orf21 as novel fusion partner for ETV1, and the heterogeneity of ETV1 gene arrangements in human prostate cancer. In a separate publication in the same year, Attard et al also identified a novel category of prostate cancers characterised by duplication of the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of 2+Edel. The authors concluded that the aforementioned genetic sequences could be part of a new mechanism-based prognostic classification for assessing the potential future aggressiveness of every human prostate cancer at diagnosis.
4) Prognostic models & scores
With regards to prognostic models, the Trans-Atlantic Prostate Group has developed various models and scores for the prediction of progression of prostate cancer and disease-specific survival. In 2008, Kattan et al developed and internally validated the first nomogram for prediction of disease-specific survival, since outcome prediction models for watchful waiting are rare relative to those available for aggressive therapies such as surgery or radiation therapy. The nomogram predicted well with a concordance index of 0.73 and had good calibration. This is an accurate tool for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counselling and clinical trial design.
There have been several papers such as Histopathologic False-positive Diagnosis of Prostate Cancer in the Age of Immunohistochemistry - The American Journal of Surgical Pathology 2018 and Validation of the cell cycle progression score to differentiate indolent from aggressive prostate cancer in men diagnosed through transurethral resection of the prostate biopsy - Cancer Reports 2021. All data collection via NHS England for the TAPG cohort contributes to the future of preventive measures and approaches to reducing the long term undesirable outcomes currently experienced for men with a prostate cancer diagnosis.
DARS-NIC-245768-V0N2T-v0.6 1 March 2020 to 28 February 2023
- Title
- MR1488: Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 3
- Files released
- 9
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics
Objective for processing
Prostate cancer is the most common cancer affecting men in the UK with over 47,000 cases in 2015, representing over a quarter of all new cancer cases in males, and was the second leading cause of cancer death in 2015. Despite its rate of incidence and mortality, men are more likely to live with prostate cancer, as overall more than 85% of men diagnosed with prostate cancer will survive for ten or more years in England and Wales.
Localised prostate cancer in particular presents unique challenges in terms of differential diagnosis, and prognosis of aggressive versus indolent cancer and optimum treatment of clinically localised prostate cancer is poorly defined. Current inability to make the distinction poses the greatest problem when deciding appropriate clinical management strategies. This inability to biologically distinguish indolent from aggressive prostate cancer has led to over-diagnosis (identification of false positives) and overtreatment (treating false positives) of prostate cancer in cases where the cancers would not have caused clinical consequences. While only half of patients have potentially high-risk prostate cancer, up to 90% of patients with low-risk prostate cancer still undergo radical prostatectomy. It is known that cancer stage at diagnosis strongly influences the choice of treatment and anxiety also impacts on treatment decisions, with men opting for active treatment rather than active management. Overtreatment of low and intermediate risk prostate cancers is therefore a concern, especially in view of recent research which has shown there is no superiority of active treatment over active management in terms of survival.
Traditionally, standard clinical factors such as Prostate-Specific Antigen (PSA), Gleason Grade (GG) and clinical stage have been used to predict clinical tumour behaviour and stratify risk for progression. In particular, PSA testing is widely used as a screening tool for prostate cancer and to determine clinical management, despite its poor specificity and positive predictive value at borderline PSA values. Although PSA can be evaluated in conjunction with GG, tumour stage and other factors to produce the Cancer of the Prostate Risk Assessment (CAPRA), there remains significant heterogeneity in outcomes within these standard groupings and the aforementioned factors are not sufficiently discriminating.
Biomarkers have the potential to discriminate between low and high-risk localised prostate cancer. They play a significant role in oncology and are a means to better understand the molecular mechanisms behind tumour growth and progression. As defined by the National Institutes of Health Biomarkers Definitions Working Group, a biomarker “is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Biomarkers can be detected in blood, urine and tissue samples and can measure macro-molecules, such as DNA and RNA, cells and other biological processes.
Biomarkers are critical in the field of prostate cancer as they can determine diagnosis and prognosis, as well as recurrence and treatment response. Novel biological and pathological markers are urgently required in order to develop more accurate prognostic models that can be routinely used in the clinical setting. These models would significantly improve clinical management strategies and patients’ decisions on diagnosis with localised prostate cancer, avoiding interventions with significant morbidity and toxicity.
The Trans-Atlantic Prostate Group (TAPG) was established to examine the hypothesis that through a detailed retrospective analysis of outcome in a group of men with clinically localised prostate cancer at diagnosis, variables such as biological, pathological and clinical markers, could be identified that might accurately predict the prognosis of clinically localised prostate cancer.
In 1999, the TAPG group initiated the “Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting” study, referred to as the TAPG study. It is a retrospective population-based tissue sample study in men diagnosed with localised prostate cancer 1990-2006, inclusively. The study began as a collaboration between Queen Mary University of London (QMUL) and Sloan Kettering hospital in New York where most biomarkers analyses were performed. Hence the study was named as “Trans-Atlantic” (and the name shortened to “TAPG” for convenience), but the recruitment of prostate cancer patients came from the UK only. Initially the cohort comprised men diagnosed with prostate cancer with transurethral resection of the prostate (TURP) and needle biopsies 1990-1996, but was expanded in 2014 to include men diagnosed with prostate cancer 1990 – 2006. Data was collected from six regional cancer registries and eligibility was confirmed via hospital sites, which sent the relevant tissue samples to the TAPG Central Coordinating Office (CCO). Selection of eligible patients for the study completed in 2010. Since that year the TAPG CCO has been collecting cancer registration and mortality updates on the cohort members from regional cancer registries.
The Sloan Kettering Hospital is now no longer involved in this study. It was involved in the early stage of the biomarker analysis phase of the TAPG study, but this work is now being carried in its entirety at QMUL.
The CCO at the Centre for Cancer Prevention (CCP) at Queen Mary University London (QMUL) seeks to continue to collect cancer and mortality data provided by NHS Digital. seeks to continue to collect cancer and mortality data via data provided by NHS Digital. The data sets returned by NHS Digital will provide the TAPG CCO with vital information on prostate cancer progression. These data sets will be linked, via a study ID and personal identifiable data, to the participants' pathology data already collected from the hospital sites at which they were diagnosed, as well as clinical data already provided from the now dissolved regional cancer registries.
The reports received from NHS Digital are essential in enabling the CCO to determine which pathological, clinical and biological markers can differentiate localised, indolent cancers from more aggressive cancers. The analyses will also enable the research community and patients to make more informed decisions on treatment pathways for prostate cancer, potentially avoiding unnecessary, highly invasive and toxic radical treatment.
Although the study will not directly benefit patients diagnosed with prostate cancer after 2006, the assessment of the prognostic model will improve the decision-making process for men diagnosed with prostate cancer in the future. If implemented clinically, men diagnosed with prostate cancer will have a more accurate risk of progression and will be able to make an informed decision on treatment options available to them and whether or not to undergo radical therapy or embark on Active Surveillance. Lack of use of prognostic factors in routine clinical practice is currently a stumbling block to the over-diagnosis and over-treatment of prostate cancer. The prognostic factors under evaluation as part of this protocol could be integrated into the clinical setting in the future, as they are compatible and complementary to other clinical tests.
As stated in the 2014 NICE guidelines on ‘Prostate cancer: diagnosis and management’: “Further research is required into the identification of prognostic indicators in order to differentiate effectively between men who may die with prostate cancer and those who might die from prostate cancer. The greatest uncertainties in managing prostate cancer are around the identification of which cancers are of clinical significance and over the choice of radical treatment, and in which settings they are appropriate. With the diagnosis of prostate cancer being made more frequently in asymptomatic men, it is of growing importance to know which of these men are likely to benefit from aggressive treatment.”
https://www.nice.org.uk/guidance/cg175/resources/prostate-cancer-diagnosis-and-management-pdf-35109753913285
Therefore there remains an unmet need in terms of identification of prognostic indicators in differentiating aggressive and indolent cancers.
The legal bases for processing this data is Article 6(1)(e) ‘performance of a task carried out in the public interest’ pursuant to the GDPR. As the research involves the use of health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing, namely article 9 (2) j which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards. This study has Health Research Authority (HRA) Confidentiality Advisory Group (CAG) ‘Section 251 support’ (CAG reference: ECC 3-06(m)/2009), which permits the processing of confidential patient information without consent and HRA Ethics approval (REC Ref. 99/3/040).
Expected output
Further outputs and analyses of the TAPG study will be published in peer-reviewed journals, such as the Lancet, Journal of Clinical Oncology, or Cancer Research and Treatment, aimed at oncologists/clinicians, researchers and health professionals working within the prostate cancer field. In addition, the research team aims to present updated long-term follow-up data at national and international prostate cancer conferences.
The public will also be made aware of findings through appropriate channels, such as a Patient and Public Involvement event; One such event was hosted in January 2020 where participants were invited in to discuss research they have been a part of, to obtain their views and opinions as to how they feel about the research carried out so far, and also find out more about the current and future work carried out at the CCP. Publications with significant findings may be accompanied by press releases and subsequent news stories.
Publications, conference attendance and results are published regularly and are available on www.qmul.ac.uk/wolfson. There is also a public Twitter account where updates will be posted on. (https://twitter.com/qmccp).
Benefits reported
YIELDED BENEFITS ACHIEVED PRIOR TO RECEIVING ANY NHS DIGITAL DATA
The use of the previously collected Registry data has allowed the research team to identify numerous cases of prostate cancer, which are a part of the TAPG cohort. Collection and processing of data from previous TAPG research has contributed directly to the primary endpoint of the trial (death from prostate cancer) and will continue to provide valuable information on understanding the pathological features of prostate cancer. It was also a useful aid in determining if the prediction of disease recurrence could be improved by the addition of other pathological, biological or molecular markers to the standard clinical factors. The data sets previously received have also helped with observing long term outcomes in men that are on Active Surveillance, thus getting a better understanding of the disease.
The Transatlantic Prostate Group has demonstrated the prognostic value of pathological, biological and molecular markers, as evidenced by the numerous publications from 2006 to present.
1) Clinical
First analysis of the first cohort of patients diagnosed with localised prostate cancer (n=2,333) from 1990 to 1996, after a 12-year median follow-up period, focussed on traditional clinical markers: Gleason Grade, serum PSA, clinical stage, as well as cancer extent in biopsy (Cuzick et al (2006)). The analysis demonstrated that Gleason score was an important determinant of cancer-specific mortality. PSA level, clinical stage and extent of disease also had predictive value. However, the study highlighted that long-term follow-up of men was necessary as it was not clear whether mortality rate trends plateau or continue to increase 15-20 years following diagnosis. Furthermore, the analysis identified that men in the cohort with an intermediate prognosis require better markers of disease progression, in order to assist in formulating appropriate management of individual men with prostate cancer.
2) Histopathological
Histo-pathological analyses of clinical markers have also generated findings of relevance to the disease area. In 2007 Berney et al examined the diagnostic accuracy and concordance with which diagnostic pathologists in the UK applied Gleason grading criteria, together with the likely consequences of the grades assigned to patient management. The objective was to test the hypothesis that the study would reveal a previous broad interpretation of Gleason grading criteria which, when applied to a large group of untreated prostate cancers and standardized according to conventional and internationally agreed criteria, would be a powerful predictor of prognosis. The study demonstrated that there was a significant error rate both in cancer diagnosis and in Gleason grading, with a significant upgrading in most biopsy and TURP specimens: 7.5% of the examined cases were reassigned to a non-malignant diagnosis. The effect of grade reassignment on the diagnosis and management of prostate cancer is considerable. Very few studies have examined the rate of misdiagnosis in prostatic cancer retrospectively, and none in such a large series as that now reported. The study highlighted that over-diagnosis of prostatic cancer is likely to have numerous consequences if the findings of this study are reflected internationally. From an individual patient’s point of view, the consequences are those of unnecessary distress, psychological impact and the significant risks of over-treatment, including hormonal therapy, radiotherapy or even radical prostatectomy.
3) Genetic
The Trans-Atlantic Prostate Group has produced analyses reporting the clinical significance of various genetic markers. In 2008 Attard et al reported CI5orf21 as novel fusion partner for ETV1, and the heterogeneity of ETV1 gene arrangements in human prostate cancer. In a separate publication in the same year, Attard et al also identified a novel category of prostate cancers characterised by duplication of the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of 2+Edel. The authors concluded that the aforementioned genetic sequences could be part of a new mechanism-based prognostic classification for assessing the potential future aggressiveness of every human prostate cancer at diagnosis.
4) Prognostic models & scores
With regards to prognostic models, the Trans-Atlantic Prostate Group has developed various models and scores for the prediction of progression of prostate cancer and disease-specific survival. In 2008, Kattan et al developed and internally validated the first nomogram for prediction of disease-specific survival, since outcome prediction models for watchful waiting are rare relative to those available for aggressive therapies such as surgery or radiation therapy. The nomogram predicted well with a concordance index of 0.73 and had good calibration. This is an accurate tool for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counselling and clinical trial design.
[The full account of studies completed and the list of bibliographies can be found in Supporting Document SD13]
Register history
When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds, the earliest of which is July 2021.
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July 2021 —
already listed in the earliest edition this site holds, so it may be older. 1 version: DARS-NIC-245768-V0N2T-v0.6
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August 2023
1 version added: DARS-NIC-245768-V0N2T-v1.4
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April 2024
1 version added: DARS-NIC-245768-V0N2T-v2.7
Cite this page
NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-245768-V0N2T, “Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting (TAPG)”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-245768-v0n2t/ (accessed [date]).
This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.
Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-245768-V0N2T to see the original rows.