(UroToday.com) The 2022 EAU annual meeting featured a joint session of the EAU, EANM, ESMO, and ESTRO societies examining modern diagnostic and therapeutic approaches in prostate cancer, including a presentation by Dr. Ursula Vogl discussing the treatment landscape of hormone sensitive recurrent M1 prostate cancer. Dr. Vogl started her presentation by noting that from a nomenclature standpoint hormone-sensitive recurring M1 prostate cancer is the same as metachronous metastatic hormone sensitive prostate cancer, which is typically stratified into low-volume and high-volume disease. Generally, patients with metachronous disease tend to have low volume when relapsing and for the most part have a better prognosis. Previous studies suggest that patients that have had prior local treatment and subsequently develop low volume metachronous metastatic disease (treated with ADT monotherapy) have a median overall survival of 7.7 years, compared to those that have had prior local treatment and subsequently develop high volume metachronous metastatic disease (4.5 years). At the recent ASCO 2022 annual meeting, the updated analyses of the ENZAMET trial showed that men with metachronous high-volume disease treated with ADT + enzalutamide had a 5-year OS rate of 60% compared to 80% for those with metachronous low-volume disease treated with ADT + enzalutamide:
Dr. Vogl notes that there is excellent evidence that patients with de novo metastatic disease benefit from all approved treatments, including 6 cycles of docetaxel, abiraterone + prednisone, enzalutamide, and apalutamide. Patients with metachronous disease (although small numbers in clinical trials) also benefit from systemic therapy in addition to ADT. As follows is a high-level summary of all overall survival hazard ratios for approved treatment for mHSPC:
There is specific evidence for treatment of metachronous mHSPC with apalutamide and enzalutamide based on subgroup analyses of the TITAN and ENZAMET trials. A meta-analysis by Sweeney et al.1 suggested that the fixed effect model hazard ratio was 0.46 (95% CI 0.30-0.70):
The PEACE-12 and ARASENS3 trials are two phase III triplet therapy trials that recently changed the treatment landscape and may change standard of care in selected patients. However, do recurrent M1 prostate cancer patients benefit from this aggressive approach? Dr. Vogl notes that the PEACE-1 trial only recruited de novo metastatic disease patients, so we are unable to derive any insight for metachronous disease patients from this trial. However, for ARASENS, patients with recurrent metastatic disease derived a benefit from darolutamide + ADT + docetaxel versus placebo + ADT + docetaxel (HR 0.61, 95% CI 0.35-1.05):
Recent data from the APCCC 2022 meeting in April 2022 suggests that there is no consensus agreement as to whether men with metachronous mHSPC should receive docetaxel based triplet therapy:
- 37% do not usually recommend this combination
- 58% only recommend this combination in high-volume metachronous mHSPC
- 5% offer triplet therapy in the majority of patients
Do we need ADT + ARTA in oligometastatic metachronous mHSPC? Is metastasis directed therapy to postpone systemic treatment in oligometastatic patients another valid approach? According to the STOMP, ORIOLE, and SABR-COMET phase 2 trials in oligometastatic low volume patients, this approach may be feasible:
Additionally, the EAU guidelines gives a strong recommendation for only offering metastasis-directed therapy to M1 patients within a clinical trial setting or well-designed prospective cohort study.
Dr. Vogl concluded her presentation by discussing the treatment landscape of hormone-sensitive recurrent M1 prostate cancer with the following take-home messages:
- Recurring M1 hormone-sensitive prostate cancer mostly presents with low-volume disease, but modern-imaging will diagnose more metachronous high-volume disease in the future
- High-level evidence exists for systemic treatment for metachronous low-volume and high-volume mHSPC (ADT plus: apalutamide, enzalutamide, docetaxel, docetaxel + darolutamide)
- For oligometastatic (<= 3 lesions) recurrent mHSPC metastasis directed therapy (ie. SABR) is a promising therapeutic approach, but does not yet have a proven OS benefit and must still be considered as experimental until the results of ongoing trials (including PSMA PET imaging) are available (ie. POSTCARD, PEACE V, STORM, DART)
Presented by: Ursula M. Vogl, MD, MBA, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.
- Sweeney CJ, Martin AJ, Stockler MR, et al. Overall survival of men with metachronous metastatic hormone-sensitive prostate cancer treated with enzalutamide and androgen deprivation therapy. Eur Urol 2021 Sept;80(3):275-279.
- Fizazi K, Foulon S, Carles J, Roubaud G, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomized, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707.
- Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142.