Lower baseline testosterone level is related to earlier development of castration resistance in metastatic prostate cancer: a multi-center cohort study.

In the era of concurrent combination therapy in metastatic hormone sensitive prostate cancer, the impact of the testosterone level before initiating androgen deprivation therapy on treatment outcome is still uncertain. We aimed to investigate its effect on time-to-castration-resistance in a metastatic hormone sensitive prostate cancer cohort.

This is a multi-center retrospective study of 5 databases from China, Japan, Austria and Spain including 258 metastatic hormone sensitive prostate cancer patients with androgen deprivation therapy initiated between 2002 and 2021. Baseline testosterone was divided into high and low groups using 12 nmol/L as cutoff level. Primary outcome was time-to-castration-resistance. Secondary outcomes were survival functions. Kaplan-Meier method was employed to evaluate the correlation between baseline testosterone and time-to-castration-resistance. Subgroup analysis was performed to elucidate the effect of upfront combination-therapy and metastatic volume.

Median age was 72 years. Median follow-up time was 31 months. Median pre-treatment prostate-specific-antigen level was 161 ng/mL. Majority of case were graded as International-Society-of-Urological-Pathology grade 5 (63.6%). 57.8% patients had high volume disease and 69.0% received upfront combination treatment. 44.6% of the cohort developed castration-resistance. The low testosterone group demonstrated shorter mean-time-to-castration-resistance (19.0 vs 22.4 months, p=0.031). The variance was more significant in patients without combination therapy (13.2 vs 26.3 months, p=0.015). Cancer-specific and overall survival were inferior in the low baseline testosterone level group without receiving combination therapy (p=0.001).

Lower pre-treatment testosterone level is correlated to shorter time-to-castration resistance and worse survival in metastatic prostate cancer patients without upfront combination therapy. Those with low baseline testosterone should be encouraged to adopt combination therapy to delay progression.

Frontiers in oncology. 2024 Feb 20*** epublish ***

Ho Ming Chris Wong, Peter Ka-Fung Chiu, Ignacio Puche-Sanz, Zhao Xue, Dong-Ning Chen, Enrique Gomez-Gomez, Isabel Heidegger, Mona Kafka, Yong Wei, Shinichi Sakamoto, Anthony Chi Fai Ng

SH Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China., Department of Urology, Hospital Universitario Virgen de las Nieves, Granada, Spain., Department of Urology, Chiba University, Chiba, Japan., Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fujian, China., Department of Urology, Medizinische Universit├Ąt Innsbruck, Innsbruck, Austria.