(UroToday.com) The 2022 ESMO annual meeting featured a prostate cancer session, including a discussant presentation by Dr. Boris Hadaschik discussing two abstracts including “Differential treatment response with nodal metastases in metastatic hormone-sensitive prostate cancer (mHSPC) and evaluation of nodal burden as a prognostic biomarker -ancillary studies of the docetaxel and abiraterone acetate and prednisolone phase III trials from STAMPEDE” presented by Dr. Áine Haran and “8-month PSA strongly predicts outcomes of men with metastatic castration-sensitive prostate cancer in the PEACE-1 phase 3 trial” presented by Dr. Gwenaelle Gravis Mescam. Dr. Hadaschik notes that the standard of care in metastatic castration-sensitive prostate cancer (mCSPC) has evolved, most recently with publication of PEACE-11 and ARASENS2:
Dr. Hadaschik first discussed the 8-month PSA outcomes in the PEACE-1 trial. In the overall population, 8 month PSA > 0.2 vs <= 0.2 ng/mL was associated with worse OS in the ADT +/- docetaxel (median 3.5 years, 95% CI 3.1-4.1 vs not evaluable, 95% CI 4.8 to not evaluable, p<0.0001) and the ADT +/- docetaxel + abiraterone acetate + prednisone arms (3.4 years, 95% CI 2.8 to 3.9 vs not evaluable, 95% CI 5.7 to not evaluable, p<0.0001):
Dr. Hadaschik notes that the efficacy of triplet therapy in this trial is evident given that 246 men were able to achieve a PSA <= 0.2 ng/mL compared to 212 with a PSA of > 0.2 ng/mL. Furthermore, those with a PSA of > 0.2 ng/mL have the same overall survival whether they received triplet (median 3.4 years, 95% CI 2.8 to 3.9) or doublet (median 3.5 years, 95% CI 3.1 to 4.1) therapy. As such, providing better options for these patients is currently an unmet need. This information is not unique to PEACE-1, as Dr. Hadaschik notes that in the ARASENS trial, men receiving triplet therapy that achieved an undetectable PSA at 24 weeks compared to those that had a detectable PSA at 24 weeks had significantly improved OS (median not evaluable, 95% CI not evaluable to not evaluable vs not evaluable, 95% CI 35.9 months to not evaluable; HR 0.47, 95% CI 0.35-0.63):
Furthermore, depth of PSA response in TITAN correlates with OS among men receiving apalutamide + ADT:
Dr. Hadaschik’s conclusions from this analysis of PEACE-1 are as follows:
- Triplet therapy is promising for high volume disease in fit men
- 8-month PSA value strong predicts outcomes in men with mCSPC
- PSA alone is not enough for clinical decision making yet, and we must carefully follow the poor responders
- Tumor characterization and treatment intensification in men with unfavorable PSA response should be investigated
Dr. Hadaschik then discussed the STAMPEDE trial data presented by Haran et al. Nodal burden indeed is a prognostic biomarker among men receiving ADT + abiraterone:
Dr. Haran’s conclusions from this trial were (i) increased nodal burden is a negative prognostic biomarker and should be considered in prospective risk/volume definitions to aid risk stratification in selected patients, and (ii) this study also demonstrates for the first time a potential differential response between mHSPC patients with nodal +/-bone metastases versus bone-only metastases for ADT + docetaxel but not for ADT + abiraterone acetate and prednisolone. Dr. Hadaschik notes that when looking at an overview of OS in phase 3 mCSPC trials focusing on “low volume” patients, the data is less convincing for docetaxel in this setting, akin to patients with nodal disease:
Dr. Hadaschik then emphasized that perhaps based on this data we need to potentially start counting lymph nodes, which is quite arduous on conventional imaging. Based on data from the proPSMA trial,3 we know that PSMA PET/CT is much more sensitive than conventional imaging for detection of lymph nodes. Additionally, retrospective work by Barbato et al.4 assessed PSMA PET versus CT imaging among 105 patients with CHAARTED-like mHSPC. There were 85 CT-based CHAARTED-low volume disease and 20 CT-based CHAARTED-high volume disease patients included. A PSMA-tumor volume of ~40 ml was the optimal cutoff between CT-based CHAARTED-low volume disease (non-unifocal) and high-volume disease (non-M1c) (AUC 0.86). Stratification into PET-low volume disease (unifocal or oligometastatic/disseminated <~40 mL) and PET-high volume disease (oligometastatic/disseminated ≥~40 mL or M1c) had 13% misalignment with CHAARTED criteria. Dr. Hadaschik notes that the EAU guidelines for patients with high-risk localized disease/locally advanced disease strongly cautions the lack of outcome data of subsequent treatment changes when using PSMA PET or whole body MRI to increase sensitivity.
Dr. Hadaschik’s conclusions from this analysis of the STAMPEDE trial are as follows:
- Docetaxel alone is not useful in patients with low-volume disease
- Counting bone lesions is not enough for patient stratification
- Modern imaging should be included in clinical trials to test if higher sensitivity and additional biologic information improves outcomes
Presented by: Boris A. Hadaschik, MD, Essen and German Cancer Consortium, University Hospital Essen, Essen, Germany
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 Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.
References:
- 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.
- Hofman MS, Lawrentschuk N, Francis, RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomized, multicentre study. Lancet 2020 Apr 11;395(10231):1208-1216.
- Barbato F, Fendler WP, Rauscher I, et al. PSMA-PET for the assessment of metastatic hormone-sensitive prostate cancer volume of disease. J Nucl Med. 2021 May 14;62(12):1747-1750.