The argument for surgical management of high-risk prostate cancer

PSA screening has enabled urologists to diagnose prostate cancer at an earlier stage. However, depending on the risk stratification used, up to one-third of newly diagnosed prostate cancer will be classified as high risk based on clinical and pathologic parameters, and are considered to be at higher risk for PSA failure, need for secondary therapy, metastatic progression, and death from systemic disease (Urol Oncol 2010; 28: 557-67).

 

High-risk prostate Ca: Definitions, treatment guidelines

D’Amico et al listed the parameters for which different risk stratifications have been based, with high-risk prostate cancer having any of the following three parameters: PSA value >20 ng/mL, biopsy Gleason score 8–10, or clinical stage >T2c (JAMA 1998; 280: 969-74). Definitions for high-risk prostate cancer tend to vary depending on the consortium, and each consortium also indicates some differences in management guidelines (table 1).

Once a patient is classified with localized, high-risk disease, one may consider performing germline genetic testing and genetic counselling, given the 6% prevalence of inherited homologous recombination gene mutations in this subset of patients (N Engl J Med 2016; 375:443-53). Such information can help in considering cancer risk syndromes, assessing for personal risk of second cancers, primary and secondary treatment selection, and predicting risk of progression after local therapy and decreased overall survival.

Also see: Apalutamide prolongs time to mets in nmCRPC

The issue of radical prostatectomy (RP) versus radiation therapy (RT) for high-risk prostate cancer remains a matter of intense debate. The majority of men with high-risk prostate cancer tend to receive external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT), which is in fact the only Category 1 treatment recommendation by the National Comprehensive Cancer Network for this setting (NCCN Clinical Practice Guidelines in Oncology/Prostate Cancer Version 2.2018; bit.ly/2kxXjIC). The guideline does note that RP with pelvic lymph node dissection (PLND) may be considered in young, healthier patients without tumor fixation to pelvic sidewall. Likewise, The United Kingdom National Institute for Health and Care Excellence (UK NICE) guidance indicates that men with high-risk localized prostate cancer should be offered a combination of radical radiotherapy and androgen deprivation therapy (BMJ 2014; 348: f7524).

Both the American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology (AUA/ASTRO/SUO) and European Association of Urology-European Society for Radiotherapy & Oncology-International Society of Geriatric Oncology-EAU Section of Urological Research (EAU-ESTRO-SIOG-ESUR) guidelines list RP with PLND and EBRT with ADT as standard treatment options for high-risk prostate cancer (J Urol 2017; Dec 15 [Epub ahead of print]; Eur Urol 2017; 71:618-29).

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