News was plentiful at the 2011 Genitourinary (GU) Cancers Symposium, held in Orlando, Florida, February 17-19. The ASCO Post will feature key reports from the meeting (see, for example, news items here and here, and watch for coverage in future issues). In addition, other noteworthy studies presented in Orlando are summarized below.
Inappropriate Use of Imaging
Despite the existence of national guidelines for imaging of men with newly diagnosed prostate cancer, physicians who treat Medicare patients are failing to adhere to the guidelines. A retrospective review of over 30,000 men in the SEER-Medicare database found that 36% of men with low-risk prostate cancer and 49% of men with intermediate-risk prostate cancer had imaging tests, all of which were inappropriate under the guidelines (abstract 120). On the other hand, 39% of men at high risk did not receive imaging according to the guidelines. Lead author Sandip Prasad, MD, University of Chicago Medical Center, estimated that the unnecessary imaging tests wasted $35 million of American taxpayers' money, which is about 10% of the total research budget for prostate cancer at NCI. When asked about the reasons for inappropriate use of imaging, he said that some physicians may be practicing defensive medicine. However, Dr. Prasad was especially concerned about high-risk men not receiving appropriate imaging.
Robotic Prostatectomy
Robotic-assisted laparoscopic radical prostatectomy is enjoying exponential growth across the United States. However, a retrospective cohort study shows that the learning curve for the procedure is much longer for certain outcomes than has been assumed, and operating times can take a large number of cases before reaching a plateau (abstract 102). The study tracked three different surgeons at three separate high-volume centers who performed a total of 3,794 such procedures between January 2003 and September 2009. It took a total of 1,600 procedures to achieve a positive surgical margin rate of < 10%, something widely considered as an expert level of proficiency by prostate cancer surgeons. Mean operating time was about 3 hours at the start of the study and plateaued at about 2 hours after about 750 cases. According to lead author Prasanna Sooriakumaran, MD, Weill Cornell Medical College, the take-home message of this study is that robotic-assisted laparoscopic radical prostatectomy should be done at high-volume centers. Surgeons who want to become proficient at the procedure should study at high-volume centers, he said.
Open-label Degarelix after Leuprolide Therapy
Open-label treatment with degarelix (Firmagon) slowed prostate-specific antigen (PSA) progression significantly in patients switched to the drug following 12 months of therapy with leuprolide (abstract 12). These results of an open-label extension study came on the heels of a pivotal phase III randomized trial comparing degarelix and leuprolide. In the original study, degarelix was superior to leuprolide in rate of suppression of androgen and PSA, risk of PSA failure or death, and reducing level of a biomarker associated with metastatic disease. The data reported at the GU Cancers Symposium were from a group of prostate cancer patients assessed by investigators as clinically appropriate for ADT and thus treated with either monthly degarelix or monthly leuprolide (approximately 200 patients per arm). Lead author Neal Shore, MD, Carolina Urologic Research Center in Myrtle Beach, South Carolina, said that the data support the durability of the significant PSA progression-free survival benefit achieved with degarelix vs leuprolide during the initial 12-month trial and was further confirmed during a 27.5-month follow-up.
Pomegranate for Rising PSA
Two different doses of pomegranate extract prolonged the PSA doubling time by 6 months in men with a rising PSA following local therapy for prostate cancer (abstract 11). Median PSA doubling time increased from 11.9 months before treatment with the pomegranate extract to 18.5 months afterward, noted lead author Michael Carducci, MD, of Johns Hopkins Kimmel Cancer Center. Approximately 13% of patients had a decline in PSA level. But about 15% to 20% of the 104 patients enrolled in the trial had a reduction in PSA doubling time prompting treatment discontinuation. Patients who had undergone any previous definitive therapy (either surgery or radiation therapy) and had a rising PSA level of > 0.4 ng/mL or higher on three separate measurements were randomly assigned to 3 daily 1,000-mg capsules of pomegranate polyphenol (equal to one 8-oz serving of pomegranate juice) or 1 capsule of the extract and 2 capsules of placebo, and treatment was continued for 18 months. The study had several limitations, including lack of a control arm, and the fact that PSA doubling time is not a proven clinically meaningful endpoint.
Cabozantinib for Bone Metastases in Prostate Cancer
Cabozantinib (XL184) achieved dramatic resolution of bone metastases after 12 weeks of treatment in the open-label lead-in period of a phase II randomized discontinuation trial, reported lead author David C. Smith, MD, of the University of Michigan Cancer Center (abstract 127). More phase II and III studies of the drug are planned. Cabozantinib is an inhibitor of tumor growth, metastasis, and angiogenesis. It simultaneously targets the key kinases MET and VEGFR2, which are involved in the development and progression of many cancers.
Resolution of bone metastases occurred in 85% of 62 patients with available bone scans, and 8 additional patients had stable disease after 12 weeks of cabozantinib treatment. At baseline, about 50% of the 100 patients entered in the trial had experienced disease progression on docetaxel, 78% had bone metastases, 50% had significant pain, and 37% required narcotics for pain. A total of 26 patients dropped out before completing 12 weeks of treatment. Of 43 evaluable patients with bone metastases and bone pain, 60% reported improvement in pain at 6 and 12 weeks of treatment with cabozantinib. Of 33 evaluable patients who required narcotics for bone pain, 21 (64%) reported improvement in pain at 6 or 12 weeks, and 13 (46%) decreased or discontinued their use of narcotics. ■
