More Stringent Monitoring of Prostate Cancer and New Treatments in Updated NCCN Guidelines

The question of whether men with low-risk prostate cancer should have their cancers vigilantly monitored is an ongoing issue for the National Comprehensive Cancer Network (NCCN) Panel on prostate cancer: The updated NCCN guidelines call for more stringent monitoring of low to very low risk prostate cancer patients who have chosen to have active surveillance rather than treatment. 

James L. Mohler, MD, chair of the NCCN Guidelines Panel for Prostate Cancer, discussed more rigorous monitoring for men not undergoing active treatment. “Active surveillance, also referred to as watchful waiting, is a viable option for many men with low-risk prostate cancer, although the concept continues to cause distress and confusion for many men, especially when they read about the controversies associated with the use of prostate-specific antigen (PSA) for the early detection of prostate cancer, noted Dr. Mohler.

Low-risk category patients have stage T1-T2a tumor, a Gleason score of 2-6, and a PSA level that's less than 10 ng/mL. Very low-risk patients have a stage T1a tumor, a Gleason score of 6 or less, a PSA level less than 10 ng/mL, fewer than three positive biopsy cores with no more than 50% cancer in each, and a PSA density that's below 0.15 ng/mL per gram.

The key debate about active surveillance versus treatment is concern for over-diagnosis and over-treatment of prostate cancer. As the NCCN Guidelines Panel chair points out, “over-treatment of prostate cancer commits too many men to side effects that outweigh a very small risk of prostate cancer death.”

Currently the NCCN guidelines recommend that high-risk men have annual PSA and prostate exams. There has been a 40% reduction of prostate cancer mortality in the U.S. since 1992. A Swedish-population trial, the Gteborg Study suggested that PSA screening reduced prostate-cancer mortality by 50%. This rate is similar to the reduction that has been seen in the U.S. 

The New Surveillance Guidelines

The current 2011 NCCN Guidelines update calls for more rigorous monitoring of men in the low -category of prostate cancer. For patients with a life expectancy of less than 20 years, PSA must be measured at least every 6 months and as often as every 3 months. Digital rectal exams must be performed at least once a year and as often as every 6 months. Needle biopsies need to be considered once a year. Repeat initial biopsies should occur within 6 months for patients with an initial biopsy that had fewer than 10 cores. The guidelines are based on expert consensus of scientific and evidence reviews and not from clinical trials.  All NCCN guidelines are available to the public at NCCN.org.

Dr. Mohler noted the issues related to active surveillance at the 16th annual NCCN conference: over-treatment, clinical risks associated with prostate biopsies, and differing criteria for active surveillance and disease progression in large clinical series. “Ultimately, this decision must be based on careful individualized weighting of a number of factors and is an option that needs to be thoroughly discussed with the patient and all of his physicians. Clearly, more clinical research is necessary to better inform decision-making,” said Dr. Mohler.

Addition of newly approved treatments to NCCN Guidelines

Provenge (sipuleucel-T), made by Dendreon Corportation is a recently approved personalized immunotherapy for asymptomatic or minimally symptomatic castration-recurrent metastatic prostate cancer. Men treated with Provenge had an extended median survival compared to those not treated.  Provenge is now a category 1 recommendation that is appropriate as salvage treatment for patients with castration-recurrent prostate cancer who have minimally symptomatic disease, an ECOG performance score of 0 or 1, and a life expectancy of at least 6 months,” noted Dr. Mohler.

The Provenge recommendation is based on the Phase 3 III IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial that showed significantly improved overall survival but not progression-free survival (N. Engl. J. Med. 2010;363:411-22). “Sipuleucel-T is not recommended for men with symptomatic disease, for whom chemotherapy with docetaxel and prednisone remains appropriate” according to Dr. Mohler.

Another update is the addition of Jevtana (cabazitaxel) made by Sanofi-Aventis for second-line in men with castration-recurrent metastatic prostate cancer who fail docetaxel.  The trial that led to the recommendation showed a 30% risk reduction of death in patients treated with Jevtana compared to those treated with mitoxantrone.

Finally, Xgeva (denosumab) from Amgen has been added to the guidelines as an alternative to Zometa (zoledronic acid) for preventing skeletal-related events.  “In men with castration-recurrent prostate cancer who have bone metastases, denosumab was shown superior to zoledronic acid in preventing disease-related skeletal complications, which include fracture, spinal cord compression, or the need for surgery or radiation therapy to bone,” said Dr. Mohler.