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JAMA Network Insights
December 27, 2018

Treatment of Metastatic Prostate Cancer in 2018

Author Affiliations
  • 1Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. 2019;5(2):263-264. doi:10.1001/jamaoncol.2018.5621

Treatment of advanced and metastatic prostate cancer has rapidly evolved with the approval of multiple agents, which improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC). In addition, there is growing evidence that use of these agents earlier in the disease course provides clinical benefit and an OS advantage. Herein, we review the shift toward earlier use of agents in the course of advanced prostate cancer.

In 2018, androgen deprivation therapy (ADT) remains the backbone of systemic therapy for prostate cancer. Use of docetaxel and abiraterone acetate were originally limited to patients with metastatic CRPC, but recently these agents have been studied in both lower- and higher-risk populations with progression of disease while not receiving ADT, or so-called hormone sensitive prostate cancer (HSPC). The use of 6 cycles of docetaxel, 75 mg/m2, in HSPC is supported by two phase 3 clinical trials (CHAARTED1 and STAMPEDE2). In both studies, early initiation of docetaxel in conjunction with ADT in patients with metastatic HSPC was associated with improved OS compared with ADT alone (CHAARTED: 57.6 vs 47.2 months; hazard ratio [HR], 0.72; 95% CI, 0.59-0.89; P = .002; STAMPEDE: 60 vs 45 months; HR, 0.76; 95% CI, 0.62-0.92; P = .005). Overall, this regimen is well tolerated. However, the role of docetaxel in patients with low-volume metastatic and nonmetastatic disease is less clear. In a subgroup analysis of CHAARTED, early docetaxel treatment was associated with improved OS (51.2 vs 34.4 months; HR, 0.63; 95% CI, 0.50-0.79; P < .001) in patients with high-volume disease (presence of visceral metastases or ≥4 bone lesions, with ≥1 beyond the vertebral body or pelvis), whereas in patients with low-volume disease, no improvement in OS was seen (63.5 vs not reached; HR, 1.04; 95% CI, 0.70-1.55; P = .86). These data are further supported by results from GETUG-AFU 15,3 a study of largely good-risk patients (ie, >50% of patients with low-volume disease), which also did not show an improvement in OS (not reached vs 83.4 months; HR, 1.02; 95% CI, 0.67-1.55; P = .90). Together, these data suggest that docetaxel should be considered for patients with more aggressive (de novo [those who initially present with metastatic disease] and/or high-volume metastatic) HSPC.

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