A Tool for Shared Decision Making on Referral for Prostate Biopsy in the Primary Care Setting: Integrating Risks of Cancer with Life Expectancy

Prostate cancer (PCa) is common, 1 in 8-11 men will be diagnosed with PCa during their lifetime.¹ However, most cases of PCa do not become clinically relevant. Once diagnosed PCa specific mortality ranges between 4% for Gleason score ≤6 and up to 12% for Gleason score ≥8.^{2, 3} Screening with PSA showed a reduction of PCa mortality, but controversially also led to an increase of indolent PCa, meaning slow growing PCa unlikely to cause problems in a man's life.^{^{4, 5}}

Currently, there is no screening program available for PCa, but recently the European Association of Urology (EAU) has published a position paper on population based screening indicating that implementation of PSA screening should be considered at a population level.⁶ Testing for PCa is a complex individually based decision making process taking into consideration competing risks from other co-morbidities when estimating a survival benefit from the early detection of clinically significant PCa. Important questions are 1. has the patient prostate cancer, 2. what is the natural history of the disease, and 3. will the patient benefit from the detection and treatment of his PCa. Because this decision making process is complex different recommendations from different general practitioners can emerge. Identification and weighing of important predictive variables are required to refer a patient for a prostate biopsy. The aim of our study was to develop a prediction tool that provides concrete uniform advice for the general practitioner on whether to refer a man for further assessment.

To construct a tool to aid the general practitioners with the shared decision making process for a biopsy referral, several data sources were obtained including the population-based Surveillance, Epidemiology and End Results (SEER) registry, and two randomized trials: the Prostate Cancer Intervention versus Observation Trial (PIVOT) and the European Randomized Study of Screening for Prostate Cancer (ERSPC). Our proposed prostate cancer prediction tool uses age, PSA, %freePSA and Charlson Comorbidity Score to provide a recommendation on referral to secondary care (e.g. prostate biopsy). The predictors included in this tool provide a balance between predictive accuracy and practical considerations. Higher clinical impact could be achieved by including e.g. DRE result and prostate volume to increase the accuracy of the prediction. Of crucial importance, however, is the inclusion of life expectancy and treatment benefit in our prediction tool. The American Society of Clinical Oncology (ASCO) and EAU concluded that prostate cancer screening with the PSA test should be considered among men with at least a 10 year life expectancy, as there is no general agreement that screening is helpful for men with less than 10 year life expectancy.^{7, 8}

In Figure 1, we have demonstrated the calculation and recommendation of the prediction using two male examples. First, a 65-year-old man without comorbidity has a PSA level of 4.0 ng/mL and %freePSA of 17%. His current risk of clinically significant prostate cancer (csPCa) on biopsy is 9% and life expectancy would be 12.3 years if csPCa is undetected and untreated. If the cancer is detected and treated, his life expectancy would increase by 20 months. Here, referral for further assessment seems indicated. However, a 75-year-old man with Charlson comorbidity index 2 with similar PSA and free PSA values would have a very limited absolute benefit (≤9 months) of early detection and treatment despite the fact that his risk for having csPCa is higher (15%). In this case, referral to secondary care is not indicated.

Although this prediction tool guides and aids general practitioners with objective recommendations, there is always the advice to not solely rely on these risk predictions, but to use it as one of the sources of relevant information in the shared decision making process. Our prediction model estimates life expectancy in different scenarios (life expectancy with/without PCa and with/without treatment for prostate cancer). However, other outcome measures can influence a decision to refer for biopsy, i.e., quality of life, disease-free LE, progression to metastatic disease or at least equally important, personal preferences. The potential role of all these factors should be studied in detail and, if applicable, considered for inclusion in prediction models. External validation of our prediction tool is certainly recommended as well as assessing the value of including new diagnostic tools such as mpMRI and promising biomarker panels.

Figure 1. Output of the prediction tool for the general practitioner. Displaying risk of csPCa; Gleason score ≥3+4) on a current biopsy, life expectancy (LE) in years with and without csPCa, treatment benefit in years and referral advice in two male examples.

Written by: Professor Monique J. Roobol, Ph.D., and Jan FM Verbeek, MD, Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands

References:
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2. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. Jama. 2005;293:2095-101.
3. Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, et al. Follow-up of Prostatectomy versus Observation for Early Prostate Cancer. N Engl J Med. 2017;377:132-42.
4. Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014;384:2027-35.
5. Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, Carter HB, et al. Overdiagnosis and overtreatment of prostate cancer. European Urology. 2014;65:1046-55.
6. Gandaglia G, Albers P, Abrahamsson PA, Briganti A, Catto JWF, Chapple CR, et al. Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019. European urology. 2019.
7. Basch E, Oliver TK, Vickers A, Thompson I, Kantoff P, Parnes H, et al. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion. J Clin Oncol. 2012;30:3020-5.
8. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. European urology. 2017;71:618-29.

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