(UroToday.com) In this session, Dr. Robert Jones discussed whether there are patients with metastatic hormone-sensitive prostate cancer (mHSPC) for whom treatment with ADT is appropriate in 2021. To frame this discussion, he considered the question from a biological and humanitarian perspective. From the biology standpoint, he posited two questions. Can we predict the absolute futility of all additional interventions? And can we predict patients where additional interventions will do more harm than good? From the human standpoint, can we predict who will survive without additional interventions, i.e., die of other causes without intervening morbidity from prostate cancer?
To begin to address these questions, Dr. Jones recapped real-world data on current treatment patterns. Despite data showing overall survival benefit for the addition of docetaxel to ADT in men with mHSPC several years earlier, only 38% of men with mHSPC were being treated with docetaxel in Scotland in 2018.1 There is no published real-world data regarding access to AR targeted agents in mHSPC, however, projected estimates suggest similar uptake in only a minority of men with mHSPC.
He moved on to address the biology question about whether we can predict the futility of specific interventions. He highlighted work from Hamid et al who performed RNA expression analysis on tumor samples from the CHAARTED study showing that men with basal subtype do not benefit from the addition of docetaxel to ADT whereas those with luminal subtype do.2 Overall, however, there is a relative paucity of data on predictive biomarkers of response to docetaxel or AR targeted agents in the mHSPC setting.
Dr. Jones then switched to the question of whether we can predict patients where additional interventions may do more harm than good. In other words, can we predict a subgroup where the prognosis is so good that they will never need additional prostate cancer therapy? A study from 2003 by Glass et al derived three prognostic risk groups based on Gleason score, PSA, extent of metastases, and performance status that stratified men with mHSPC into good, intermediate and poor-risk groups.3 However, even the good risk group had a median overall survival of 48 months. A more recent stratification based on genomic copy number alterations is more promising. Men in the lowest group of genomic instability demonstrated a median survival of greater than 10 years.
In addition to considering prognostic information related to prostate cancer, Dr. Jones counseled on the importance of considering competing risk. He advocated for the use of online tools to better predict non-prostate cancer mortality. He concluded by acknowledging that intensification of systemic therapy is appropriate for most men with mHSPC in 2021. While there is likely a subgroup of patients who will not benefit from current therapies, at present, we lack the tools to identify who they are. Most patients with mHSPC will ultimately suffer morbidity and mortality from prostate cancer, however, Dr. Jones is hopeful that better prognostication tools and better tools to understand life expectancy from competing causes may enable us to intelligently select those who will not.
Presented by: Professor Robert Jones, Professor of Clinical Cancer Research at the University of Glasgow
Written by: Jacob Berchuck, MD, Genitourinary Medical Oncologist, Dana-Farber Cancer Institute (Twitter: @jberchuck) during the 2021 Advanced Prostate Cancer Consensus Conference, Saturday, October 9, 2021.
References:
- Rulach RJ, et al. Real-world uptake, safety profile and outcomes of docetaxel in newly diagnosed metastatic prostate cancer. BJU Int. 2018 Feb;121(2):268-274.
- Hamid AA, et al. Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial. Ann Oncol. 2021 Sep;32(9):1157-1166.
- Glass TR, et al. Metastatic carcinoma of the prostate: identifying prognostic groups using recursive partitioning. J Urol. 2003 Jan;169(1):164-9.