March 07, 2016
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Metastatic site affects advanced prostate cancer survival

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Survival outcomes among men with metastatic castration-resistant prostate cancer appeared directly related to the site of metastasis, according to the results of a meta-analysis.

Patients with lymph node metastasis appeared to achieve the longest OS, whereas men with liver metastasis had the poorest outcomes, results showed.

“Smaller studies had given doctors and patients indications that the site of metastasis in prostate cancer affects survival, but prevalence rates in organ sites were small, so it was difficult to provide good guidance,” Susan Halabi, PhD, professor of biostatistics and bioinformatics at Duke University School of Medicine, said in a press release. “With the large numbers we analyzed in our study, we were able to compare all of these different sites and provide information that could be helpful in conveying prognosis to patients.”

Halabi and colleagues evaluated data from nine phase 3 clinical trials — encompassing 8,820 men (median age, 68 years) with metastatic prostate cancer  — conducted between 1999 and 2012 to determine the influence of metastatic site on OS. They further sought to test the hypotheses that patients with lung metastases would have a shorter median OS than patients with bone metastases, and that patients with liver metastases would have a shorter median OS than patients with lung metastases.

All enrolled men received docetaxel chemotherapy.

The researchers included four categories of metastases in their analysis: lymph node metastases only (6.4%; n = 565); bone metastases, with or without lymph node involvement, with no visceral metastases (72.8%; n = 6,356); any lung metastases, without liver involvement (9.1%; n = 791); and any liver metastases (8.6%; n = 752).

Median follow-up among surviving patients was 21.8 months (range, 0-91.2).

Overall, men with liver metastases demonstrated the poorest OS outcomes, with a median OS of 13.5 months (95% CI, 12.7-14.4).

Men with lung metastases had a median OS of 19.4 months (95% CI, 17.8-20.7), whereas men with non-visceral bone metastases had a median OS of 21.3 months (95% CI, 20.8-21.9).

The pooled multivariate HR for death among men with lung metastases vs. bone metastases with or without lymph node metastases was 1.14 (95% CI, 1.04-1.25). Men with any liver metastases also demonstrated an increased risk for death compared with men with lung metastases (HR = 1.52; 95% CI, 1.35-1.73).

Researchers also conducted secondary analyses to estimate median OS in other categories for metastatic sites. Results showed men with only lymph node metastases had the longest median OS (31.6 months; 95% CI, 27.9-35.5), whereas men with any visceral disease had the lowest median OS (16.3 months; 95% CI, 15.6-17.3).

The researchers acknowledged limitations of their meta-analysis, including their inability to include data from the most recent clinical trials of men with metastatic prostate cancer. Further, they were unable to conduct central reviews of imaging or imaging reports from these trials.

They also noted that most of these trials were conducted before the approval and broad use of abiraterone acetate (Zytiga, Janssen) or enzalutamide (Xtandi; Astellas, Medivation), which have largely replaced chemotherapy as the front-line treatment of metastatic castration-resistant prostate cancer.

“These results should help guide clinical decision-making for men with advanced prostate cancer,” Halabi said. “They also suggest that prognostic subgroups should be considered for investigational therapies that are tested in clinical trial.” – by Cameron Kelsall

Disclosure: Halabi is a consultant for Bayer and Genentech. Please see the full study for a list of all other researchers’ relevant financial disclosures.