Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide

Mamta Parikh; Catherine Tangen; Maha H A Hussain; Shilpa Gupta; Sam Callis; Yeonjung Jo; Andrea Harzstark; Channing J Paller; Saby George; Matthew R Zibelman; Heather H Cheng; Benjamin L Maughan; Jingsong Zhang; Russell K Pachynski; Alan H Bryce; Daniel W Lin; David I Quinn; Seth P Lerner; Ian M Thompson; Tanya B Dorff; Primo N Lara; Neeraj Agarwal

doi:10.1016/j.euo.2024.03.001

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide

Eur Urol Oncol. 2024 Mar 23:S2588-9311(24)00054-3. doi: 10.1016/j.euo.2024.03.001. Online ahead of print.

Authors

Mamta Parikh¹, Catherine Tangen², Maha H A Hussain³, Shilpa Gupta⁴, Sam Callis², Yeonjung Jo⁵, Andrea Harzstark⁶, Channing J Paller⁷, Saby George⁸, Matthew R Zibelman⁹, Heather H Cheng¹⁰, Benjamin L Maughan⁵, Jingsong Zhang¹¹, Russell K Pachynski¹², Alan H Bryce¹³, Daniel W Lin¹⁰, David I Quinn¹⁴, Seth P Lerner¹⁵, Ian M Thompson¹⁶, Tanya B Dorff¹⁷, Primo N Lara¹⁸, Neeraj Agarwal⁵

Affiliations

¹ UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. Electronic address: mbparikh@ucdavis.edu.
² SWOG Statistics and Data Management Center, Seattle, WA, USA.
³ Northwestern University, Chicago, IL, USA; Robert H Lurie Comprehensive Cancer Center, US.
⁴ Cleveland Clinic, Cleveland, OH, USA.
⁵ University of Utah, Salt Lake City, UT, USA.
⁶ Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.
⁷ Johns Hopkins University, Baltimore, MD, USA.
⁸ Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁹ Fox Chase Cancer Center, Philadelphia, PA, USA.
¹⁰ University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹¹ Moffitt Cancer Center, Tampa, FL, USA.
¹² Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹³ City of Hope, Goodyear, AZ, USA.
¹⁴ USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
¹⁵ Baylor College of Medicine, Houston, TX, USA.
¹⁶ University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
¹⁷ City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
¹⁸ UC Davis Comprehensive Cancer Center, Sacramento, CA, USA.

PMID: 38523017
DOI: 10.1016/j.euo.2024.03.001

Abstract

Background: A robust decrease in prostate-specific antigen (PSA) in response to androgen deprivation therapy (ADT) has been evaluated as a prognostic factor in patients with metastatic hormone-sensitive prostate cancer (mHSPC) since 2006, but the treatment of mHSPC has since evolved to include intensified therapy.

Objective: We assessed the association of PSA levels at 3 (PSA-3mo) and 7 (PSA-7mo) mo with overall survival (OS) in patients with mHSPC treated with ADT combined with either bicalutamide or orteronel in the S1216 phase 3 clinical trial.

Design, setting, and participants: PSA responses to treatment of patients in the S1216 trial were categorized as: complete response (CR) if PSA was ≤0.2 ng/ml, partial response if PSA was >0.2 and ≤4 ng/ml, and no response (NR) if PSA was >4 ng/ml.

Outcome measurements and statistical analysis: A Cox analysis (adjusted for treatment arm and three stratification factors: performance status, severity of disease, and early vs late induction) was used for OS association. While PSA-7mo association was a prespecified objective, PSA-3mo association was also evaluated.

Results and limitations: A total of 1251 and 1231 patients from the S1216 study were evaluable for PSA-3mo and PSA-7mo, respectively. A PSA-7mo CR was associated with improved OS compared with NR (HR: 0.20; p < 0.0001). A PSA-3mo CR showed a similar association to NR (HR: 0.34; p < 0.0001). The association of a PSA response with survival did not differ by treatment arm at either time point.

Conclusions: The PSA-3mo and PSA-7mo responses were strongly associated with OS; taken with other emerging prognostic biomarkers, these markers may allow for early identification of patients at the highest risk of death, aid with counseling in clinical practice, and permit design of future clinical trials targeting these patients.

Patient summary: A low prostate-specific antigen level at 3 or 7 mo after starting treatment for metastatic hormone-sensitive prostate cancer predicts longer survival regardless of the first treatment given with androgen deprivation therapy.

Keywords: Biomarker; Castration sensitive; Hormone sensitive; Prostate cancer; Prostate-specific antigen.