Most patients, 72.8%, had bone with or without lymph node metastases (n = 6356), followed by visceral disease, 20.8% (n = 1815), and lymph node-only disease, 6.4% (n = 565). Due to the small sample size, the 3% of patients with adrenal, brain, kidney, or unspecified visceral metastases were excluded from hypothesis testing.

Of 8736 men included in the meta-analysis, median age was 68 years (range, 63 – 74 years), 74% were white, 94% had a performance status of 0 or 1, median prostate specific antigen was 86.0 ng/mL (range, 31 – 250), median alkaline phosphatase was 138 U/L (range, 86 – 287), and median hemoglobin was 12.9 (range, 11.7 – 14.1). Median follow-up among survivors was 21.8 months (range, 0 – 91.2 months), and there were 5470 deaths.


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“Among patients with visceral disease, 791 (9.1%) had lung metastases and 752 (8.6%) had liver metastases,” Dr Halabi and colleagues reported. The 173 patients who had both liver and lung disease were grouped with those in the liver group.

Median overall survival was 31.6 months (range, 27.9 – 35.5) for patients with lymph node only metastases, 21.3 months (range, 20.8 – 21.9) for bone, 19.4 months (range, 17.8 – 20.7) for lung, and 13.5 months (range, 12.7 – 14.4) for liver metastases, they found.

Pooled hazard ratios were 1.14 (95% CI, 1.04 – 1.25; P = .007) for death in men with lung metastases compared with those with bone with or without lymph node metastases and 1.52 (95% CI, 1.35 – 1.73; P < .0001) in men with any liver metastases compared with men with lung metastases.

“The heterogeneity of men with mCRPC enrolled onto trials, and the substantially different outcomes among these subgroups highlight the importance of reporting overall survival by disease location,” they noted.

“These data suggest that the distribution of patients across the following categories should be routinely reported: lymph node-only disease, bone with or without lymph node involvement with no visceral metastases, and lung metastases (but no liver), and any liver metastases.”

Currently, the Prostate Cancer Clinical Trials Working Group recommends reporting of end points by metastatic site; however, only recently has this recommendation been implemented in several phase 3 trials.

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Dr Halabi told Cancer Therapy Advisor that the challenge now is to “provide the right treatment at the right time that will help patients. The results highlight the gap in understanding the biological differences by site of metastases and may lead to new research that will help bridge the gap.”

Reference

  1. Halabi S, Kelly WK, Ma H, et al. Meta-analysis evaluating the impact of site of metastases on overall survival in men with castration-resistant prostate cancer [published online ahead of print March 7, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.7270.