Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men with Castration-Resistant Prostate Cancer

PURPOSE: Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.

PATIENTS AND METHODS: Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases.

RESULTS: Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with men with liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared with men with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P < .0001), respectively.

CONCLUSION: Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.


J Clin Oncol. 2016 May 10;34(14):1652-9. doi: 10.1200/JCO.2015.65.7270. Epub 2016 Mar 7.

Authors:

Halabi S1, Kelly WK2, Ma H2, Zhou H2, Solomon NC2, Fizazi K2, Tangen CM2, Rosenthal M2, Petrylak DP2, Hussain M2, Vogelzang NJ2, Thompson IM2, Chi KN2, de Bono J2, Armstrong AJ2, Eisenberger MA2, Fandi A2, Li S2, Araujo JC2, Logothetis CJ2, Quinn DI2, Morris MJ2, Higano CS2, Tannock IF2, Small EJ2.

Author Information:

1. Susan Halabi, Hua Ma, Nicole C. Solomon, and Andrew J. Armstrong, Duke University, Durham, NC; William Kevin Kelly, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Haojin Zhou, Merck, Beijing, China; Karim Fizazi, Institut Gustave Roussy, University of Paris Sud, Villejuif, France; Catherine M. Tangen, Southwest Oncology Group Statistical Center; Mark Rosenthal, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Daniel P. Petrylak, Yale Cancer Center, New Haven, CT; Maha Hussain, University of Michigan, Ann Arbor, MI; Nicholas J. Vogelzang, US Oncology, Las Vegas, NV; Ian M. Thompson, University of Texas at San Antonio, San Antonio; John C. Araujo and Christopher J. Logothetis, The University of Texas MD Anderson Cancer Center, Houston, TX; Kim N. Chi, British Columbia Cancer Agency-Vancouver Cancer Centre, Vancouver, British Columbia; Ian F. Tannock, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; Johann de Bono, Institute for Cancer Research, Royal Marsden Hospital, Sutton, Surrey, United Kingdom; Mario A. Eisenberger, Johns Hopkins University-School of Medicine, Oncology Center, Baltimore, MD; Abderrahim Fandi and Shaoyi Li, Celgene Corporation, Summit, NJ; David I. Quinn, University of Southern California Norris Cancer Center, Los Angeles; Eric J. Small, University of California San Francisco, San Francisco, CA; Celestia S. Higano, University of Washington, Seattle, WA; and Michael J. Morris, Memorial Sloan-Kettering Cancer Center New York, NY.

2. Susan Halabi, Hua Ma, Nicole C. Solomon, and Andrew J. Armstrong, Duke University, Durham, NC; William Kevin Kelly, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Haojin Zhou, Merck, Beijing, China; Karim Fizazi, Institut Gustave Roussy, University of Paris Sud, Villejuif, France; Catherine M. Tangen, Southwest Oncology Group Statistical Center; Mark Rosenthal, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Daniel P. Petrylak, Yale Cancer Center, New Haven, CT; Maha Hussain, University of Michigan, Ann Arbor, MI; Nicholas J. Vogelzang, US Oncology, Las Vegas, NV; Ian M. Thompson, University of Texas at San Antonio, San Antonio; John C. Araujo and Christopher J. Logothetis, The University of Texas MD Anderson Cancer Center, Houston, TX; Kim N. Chi, British Columbia Cancer Agency-Vancouver Cancer Centre, Vancouver, British Columbia; Ian F. Tannock, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; Johann de Bono, Institute for Cancer Research, Royal Marsden Hospital, Sutton, Surrey, United Kingdom; Mario A. Eisenberger, Johns Hopkins University-School of Medicine, Oncology Center, Baltimore, MD; Abderrahim Fandi and Shaoyi Li, Celgene Corporation, Summit, NJ; David I. Quinn, University of Southern California Norris Cancer Center, Los Angeles; Eric J. Small, University of California San Francisco, San Francisco, CA; Celestia S. Higano, University of Washington, Seattle, WA; and Michael J. Morris, Memorial Sloan-Kettering Cancer Center New York, NY.