(UroToday.com) In an interactive session of the American Society for Radiation Oncology (ASTRO) Annual Congress focussing on the management of patients with Intermediate Risk Prostate Cancer from initial consultation through treatment to follow-up, Dr. Neil Desai presented on the conundrum that is intermediate prostate cancer: while we have a wealth of choices, this can make treatment decision making difficult.
Dr. Desai began with the case of a 62-year-old man with mild lower urinary tract symptoms and good erectile function who presents with an elevated screening PSA of 6.2 ng/mL. On biopsy, this gentleman is found to have cT1c, ISUP grade group 3 cancer in 3 of 12 cores. He then considered the role of mpMRI for initial disease evaluation in patients such as this gentleman with intermediate risk prostate cancer. He highlighted that mpMRI has many advantages including delineation of prostate and tumor anatomy, tumor staging, and correlation with tumor grade. However, there is substantial health system cost associated with the widespread use of mpMRI. Additionally, there is substantial heterogeneity between MRI studies, including due to the use of 1.5 T v 3 T magnets, biparametric versus multi-parametric imaging using contrast enhancement, and variability in reporting and interpretation of the studies. Further, he suggested that there may be overdiagnosis and potentially over-staging associated with the use of MRI. Highlighting this, he showed that not all patients with T3a disease have equivalent outcomes and that the adverse prognostic ability of this finding may be less when it is diagnosed based on MRI. However, he emphasized data from the STHLM3 consortium emphasizing the value of MRI for pre-diagnostic biopsy evaluation.
Moving to data from the ProtecT trial, he emphasized that prostate cancer mortality was only 1% at 10 years, regardless of treatment approach. Thus, this demands humility in all local therapy approaches for patients with localized prostate cancer. He further emphasized that the main comparative differences between surgery and radiotherapy relate to the type and timeline of side effect symptoms and the need for multi-modal therapy. Considering further data from the CEASAR cohort, he emphasized the principle that “if we must treat, how do we achieve the best chance of cure and quality of life at first treatment?”.
In the context of intermediate risk prostate cancer, he emphasized that this accounts for approximately 45% of new cases and 20% of all prostate cancer deaths. Further, there is considerable heterogeneity within this group with significant differences in outcomes (including metastasis rates) between patients with favourable or unfavourable intermediate risk disease. Additionally, this subgroup of prostate cancer patients has contributed to rapid accrual in many radiotherapy trials.
Even among radiotherapy approaches, patients with intermediate risk disease have a variety of guideline-concordant treatment options according to the NCCN clinical practice guidelines. These include external beam radiotherapy whether given with moderate hypofractionation which is preferred, conventional fractionation, or ultra-hypofractionation; brachytherapy monotherapy whether low dose rate or high dose rate, for patients with favourable intermediate risk disease; and EBRT + brachytherapy boost (again, either low dose rate or high dose rate) for those with unfavourable intermediate risk disease.
This wealth of treatment options, in addition to surgical and other approaches, may be at times overwhelming. Further, among patients with unfavourable intermediate risk disease, there is the question of the role of short-term androgen deprivation therapy. While this may contribute to disease control, there is a significant treatment burden of toxicity, and patient reported outcomes to suggest at least one year to 18 months of decreased quality of life (as measured on the hormonal domain of the EPIC-26) for patients who receive 6 months of ADT.
When risk-stratified according to NCCN criteria, Dr. Desai emphasized that the majority will be either over-treated or under-treated, with a relative inability to distinguish these a priori.
Genomic risk models offer the potential to improve the personalization of care and improve patient outcomes. Certainly, work to date has suggested that the Decipher score may risk stratify patients with unfavourable intermediate risk disease in terms of their risk of metastasis. The NRG GU-010 trial (GUIDANCE) will seek to better define the role of Decipher in the treatment de-escalation or intensification of patients with unfavourable intermediate risk prostate cancer.
Presented by: Neil Desai, MD, MHS, Associate Professor of Radiation Oncology, UT Southwestern Medical Center
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.