(UroToday.com) In the Society of Urologic Oncology plenary session held at the American Urologic Association Annual Meeting, Dr. Kelvin Moses addressed controversies in the management of high-risk prostate cancer.
Dr. Moses began by highlighting the NCCN definition of both high risk and very high-risk prostate cancer.
This updated definition differs somewhat from the classic D’Amico categorization based on any of a PSA greater than 20 ng/mL, a Gleason score of 8 or greater, and clinical stage T2c or greater.
Again highlighting the NCCN guidelines, he discussed a summary of treatment options. For those with high- and very high-risk prostate cancer, he emphasized that both radiotherapy and surgery-based options are appropriate, with observation reserved for those who are asymptomatic and have less than 5 year life expectancy. For patients treated with radiotherapy, external beam radiotherapy with 18-36 months of androgen deprivation therapy is the standard though consideration of the addition of brachytherapy or docetaxel (among those with very high risk disease) should also be considered. For those opting for surgery, a pelvic lymphadenectomy is recommended. ADT monotherapy can also be considered for those with poor life expectancy.
Citing the ProPSMA data, Dr. Moses considers the question of how many patients with high- and very-high-risk disease may have occult metastatic disease. In this trial, patients underwent pre-operative PSMA. The study included patients with Gleason grade group 3-5, PSA 20 or greater, or cT3/4 disease. With a composite gold standard, 30% of patients had pelvic nodal or distant metastasis. PSMA-PET/CT had substantially higher accuracy in diagnosing this compared with conventional staging studies.
Dr. Moses then moved to consider the question of “what is the best treatment for high-risk prostate cancer”. He first cited data from the CALBG 90203 trial of radical prostatectomy with or without neoadjuvant chemohormonal therapy. This study included patients with high-risk disease and notably allowed those with positive surgical margins to receive adjuvant therapy. While the primary endpoint was 3-year biochemical progression-free survival, nearly half of men (48%) received salvage therapy before reaching this endpoint. Perhaps, for this reason, the study showed no significant difference in 3-year bPFS (0.89 vs 0.84, p=0.11) though men in the neoadjuvant arm had improvements in both event-free survival and overall survival. However, rates of grade 3 and 4 toxicity were 26% and 19%, respectively, pre-operatively. Thus, the PUNCH authors concluded that these data do not support the routine use of neoadjuvant chemohormonal therapy.
He then cited a recent systematic review from Moris et al. considering the benefits and risk of local primary treatments in high-risk localized prostate cancer. Among 90 included studies, there has a high risk of bias in the data. However, low-quality evidence suggested that surgery may be preferable to radiotherapy. In particular, surgery should be considered as part of a multi-modal regime. EBRT and long-term ADT may also be recommended and EBRT with brachytherapy could also be considered though there is an increased rate of grade 3 toxicity.
Dr. Moses then considered the question of whether we can predict recurrence and response to treatment. Highlighting data from Dr. Friedlander, he showed evidence that circulating tumor cells may be prognostic for time to biochemical recurrence, albeit based on a small sample of 37 patients undergoing radical prostatectomy for high-risk disease. Additionally, these CTC could be used to identify copy number aberrations and genomic changes such as AR expression, MYC amplification, and CHD1 loss. Interestingly, these genomic changes were often discordant with the primary tumor suggesting that the CTC expression may capture clonally independent metastatic sites and better capture long-term tumor behaviour.
He then presented further data from Dr. Rangel-Pozzo and colleagues showing that CTC genetic variation and copy number alteration was heterogeneous, including with intra-patient variation. However, these variations could be used to identify patients who were responsive to docetaxel.
In conclusion, Dr. Moses emphasized that high-risk disease represents 15% of patients diagnosed with localized prostate cancer and early identification of high-risk characteristics and the extent of disease may allow for tailored therapy. However, most will benefit from a multi-modal approach.Presented by: Kelvin A. Moses, MD, PhD, Associate Professor, Vanderbilt University Medical Center
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.