Metastatic Hormone-Sensitive Prostate Cancer: Analyses and Emerging Data
Daniel P. Petrylak, MD, comments on new and emerging data on the assessment and treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) based on studies presented at AUA2021 and the ESMO Congress 2021.
Featured expert Daniel P. Petrylak, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD, and Dr Petrylak’s perspectives are presented here.
Professor of Medicine (Medical Oncology) and Urology
“. . . guidelines on advanced prostate cancer recommend that patients with mHSPC be offered continuous ADT in combination with either an androgen pathway–directed therapy or chemotherapy.”
The current standards of care for systemic treatments for mHSPC are based on trials such as CHAARTED, STAMPEDE, and LATITUDE, as discussed at AUA2021. Important data from these and other trials continue to emerge. Shortly after AUA2021, at the ESMO Congress 2021, Fizazi et al presented data from the PEACE-1 trial, which revealed the 2.5-year extension of time to radiographic progression or death and the 1.5 years of survival gains observed in men with de novo high-volume mHSPC treated with androgen deprivation therapy (ADT) and docetaxel plus abiraterone. These data likely represent a shift in the standard of care for that patient population.
Unfortunately, there appears to be a gap between existing recommendations and real-life clinical practice in monitoring for metastatic disease and treating it. The American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology guidelines on advanced prostate cancer recommend that patients with mHSPC be offered continuous ADT in combination with either an androgen pathway–directed therapy or chemotherapy. It appears as though this practice has not been as widely adopted as it should have been. We need to understand the reasons for this gap because treatment makes a big difference in overall survival. Data from key trials continue to be strong. For instance, in the ARCHES trial, which was presented at AUA2021, enzalutamide plus ADT for mHSPC significantly prolonged radiographic progression-free survival (abstract PD34-07).
The imaging-based assessment of mHSPC is an evolving area. Some have suggested that whole-body magnetic resonance imaging (MRI) may improve patient stratification for treatment delivery. Another study presented at AUA2021 (abstract MP11-16) suggested that whole-body MRIs might be superior to quantitative bone scans and that high total diffusion volume might be used to identify candidates for upfront intensive therapy. Since only 22 patients were enrolled in the study, it is difficult to make any definitive conclusions. I do not use whole-body MRI in this way in my practice; I generally use both quantitative MRI and bone scans. An issue with any modality may be the optimal frequency of scanning, and, with prostate-specific membrane antigen–directed imaging on the rise, this area will continue to evolve.
There continues to be efforts to better understand which patients might benefit from maximized androgen receptor inhibition or from the early use of antimicrotubule agents. The authors of a study analyzing the transcriptomic landscape of advanced prostate cancer found that the ratio of prostate-specific antigen to prostatic acid phosphatase might be a useful tool in this regard, although the findings will need to be validated (abstract MP60-18).
One more recent development is the recommendation for germline testing and genetic counseling for patients with mHSPC, regardless of age and family history. I agree with the importance of such screening because we do see patients with prostate cancer who have no family history in whom BRCA mutations are discovered, and identifying these mutations can lead to the eligibility for a clinical trial or it may guide treatment toward poly (ADP-ribose) polymerase inhibitors, immunotherapy, or early cytotoxic chemotherapy. It is also important to note that, because of the familial implications of germline testing, as in the case of BRCA mutations, there are important implications for genetic counseling/cancer screening in the siblings and children as well.
Fizazi K, Galceran JC, Foulon S, et al. A phase III trial with a 2x2 factorial design in men with de novo metastatic castration-sensitive prostate cancer: overall survival with abiraterone acetate plus prednisone in PEACE-1 [abstract LBA5_PR]. Abstract presented at: ESMO Congress 2021; September 16-21, 2021.
Fizazi K, Tran NP, Fein L, et al; LATITUDE Investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi:10.1056/NEJMoa1704174
Han H, Cho NH, Kang S, et al. Prostate epithelial genes define docetaxel-sensitive prostate cancer molecular subtype [abstract MP60-18]. Abstract presented at: AUA2021; September 10-13, 2021.
Iwamura H, Ito J, Hatakeyama S, et al. Comparison of quantitative whole-body MRI and bone scan for the prognosis of patients with metastatic hormone-naive prostate cancer: a prospective study [abstract MP11-16]. Abstract presented at: AUA2021; September 10-13, 2021.
James ND, de Bono JS, Spears MR, et al; STAMPEDE Investigators. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338-351. doi:10.1056/NEJMoa1702900
Lowrance WT, Breau RH, Chou R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline PART I. J Urol. 2021;205(1):14-21. doi:10.1097/JU.0000000000001375
Lowrance WT, Breau RH, Chou R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline PART II. J Urol. 2021;205(1):22-29. doi:10.1097/JU.0000000000001376
Shore ND, Iguchi T, Villers A, et al. Enzalutamide in metastatic hormone-sensitive prostate cancer patients who received prior antiandrogen therapy: post hoc analysis of ARCHES [abstract PD34-07]. Abstract presented at: AUA2021; September 10-13, 2021.
Sweeney CJ, Chen Y-H, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi:10.1056/NEJMoa1503747
Yadav S, Hart SN, Hu C, et al. Contribution of inherited DNA-repair gene mutations to hormone-sensitive and castrate-resistant metastatic prostate cancer and implications for clinical outcome. JCO Precis Oncol. 2019;3:PO.19.00067. doi:10.1200/PO.19.00067
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