Inflammation May Activate Antitumor Mechanism

466 | CANCER DISCOVERY MAY 2016 www.aacrjournals.org An international team of researchers— led by Susan Halabi, PhD, a professor of biostatistics at Duke University School of Medicine in Durham, NC—gathered information from nine phase III studies, encompassing 8,736 men with mCRPC. The patients in these trials had all received docetaxel as standard therapy. The researchers classifi ed them into one of four groups corresponding to the site of metastases: bone, liver, lungs, and lymph nodes. Most (72.8%) had bone metastases; another 8.6% and 9.1% had metastatic lesions in the liver and lungs, respectively, while those with lymph node metastases made up the smallest group (6.4%). The researchers confi rmed earlier studies identifying visceral disease— liver and lung metastases—as a negative prognostic factor of survival. Patients with liver metastases fared worst, with a median OS of just 13.5 months; those with lung metastases had a slightly longer median OS of 19.4 months. In contrast, patients with disease involving bone or lymph nodes had median survival times of 21.3 and 31.6 months, respectively. Anthony D’Amico, MD, PhD, chief of genitourinary radiation oncology at Dana-Farber/Harvard Cancer Center in Boston, MA, suggests that particular variants of mCRPC could explain the poorer survival of patients with visceral disease. “Classic prostate adenocarcinomas have a penchant for bone-only metastases,” he explains. “Certain other prostate tumors, though, have a mixed histology that includes a neuroendocrine or small-cell component. These readily spread to internal organs like the liver and lungs and are associated with a worse prognosis.” Recent research has shown that even classic prostate adenocarcinomas can acquire neuroendocrine expression over time, he adds. Distinguishing neuroendocrine and small-cell prostate cancer from adenocarcinoma is important, D’Amico says, because approved hormone therapies like abiraterone acetate (Zytiga; Janssen) and enzalutamide (Xtandi; Astellas) are not effective against these variants. Rather, “you want to consider chemotherapy that’s used in such histologies—platinum drugs, for instance, or etoposide.” The study researchers think the signifi cantly different outcomes seen with these four subgroups highlight the importance of reporting end points, including OS, by metastatic site—although this has yet to be widely implemented in phase III studies of mCRPC. D’Amico agrees, adding that “future trials should be directed based on the biopsy of a patient’s metastatic lesion, so we know exactly what we’re dealing with and can fi gure out the best treatment.” –Alissa Poh ■