BY JUDD W. MOUL, M.D.
The National Comprehensive Cancer Center guidelines are extremely useful for clinicians practicing cancer care. While the guidelines offer great advice and update the literature on various patterns of care, they are guidelines, however, and as such do offer some flexibility in the way individual clinicians manage their individual patients. Having said that, I must add that these latest updates to the NCCN guidelines on prostate cancer are especially valuable.
With regard to early-stage prostate cancer, the new guidelines offer additional recommendations regarding active surveillance. Active surveillance is growing in popularity among men with very-early, low-risk, low-stage prostate cancer. As a busy clinician in practice that is about 90% related to prostate cancer, I have found that particularly over the last year or two, more patients are getting comfortable electing active surveillance – and more doctors seem willing to monitor patients on this approach.
The challenge, as Dr. James Mohler has pointed out, is in the lack of quality evidence. We are still awaiting results from phase III trials to determine the optimal way to follow men on active surveillance. In the meantime, the current guidelines provide further guidance on using PSA, digital rectal exam, and repeat biopsy to monitor these patients, of whom I find the most challenging are young men who have low- or very-low-risk prostate cancer.
The conundrum is that, while we believe the prostate cancer has been detected at a very early nonlethal state, these patients still face a very long life expectancy, and uncertainties remain as to whether active surveillance is the best approach vs. proceeding to direct active treatment. Even though these patients may face overtreatment with radical prostatectomy or radiotherapy for this very-low-risk disease, treating young men with very-low-risk disease provides an opportunity for the least-morbid treatment.
Specifically, the younger the man is and the earlier the stage of disease, the less likely he is to experience side effects after nerve-sparing prostatectomy. We find that young men have the best chance of gaining full urinary control and of gaining erectile function. Yet, we still face the dilemma that some of these men may be overtreated, if we remove their prostate for very-low-risk disease.
The NCCN guidelines also address incorporating new agents to treat advanced prostate cancer. 2010 was a very good year for advanced prostate cancer.
The following three new pharmaceutical agents were approved, which would appear to be a record in the modern era, considering that it had been several years since the last new agent was indicated for these patients:
• In April of 2010, sipuleucel-T (Provenge) was FDA approved to treat asymptomatic or minimally symptomatic men with very-early castrate-resistant prostate cancer. The new NCCN guidelines address use of sipuleucel-T in the setting of early castrate-resistant disease.
• In June of 2010, cabazitaxel (Jevtana) was FDA approved to treat advanced prostate cancer patients who had had cancer progression despite docetaxel-based chemotherapy. This drug was approved based on the TROPIC trial, which showed an improvement in overall survival in those patients who received cabazitaxel and prednisone, compared with patients treated with mitoxantrone (Novantrone) and prednisone. This new chemotherapy advance received very rapid FDA approval, and the NCCN guidelines now articulate its use in advanced disease.
• The third agent, denosumab (Xgeva), was FDA approved in November of 2010. This new biologic agent, a RANK-ligand inhibitor, is given subcutaneously every month, and has been shown to be superior to zoledronic acid in preventing the first onset and the continuation of skeletal-related events in men with advance prostate cancer as well as in other malignancies.
All three of these agents add to our armamentarium to better manage patients with advanced prostate cancer. We applaud the NCCN for rapidly incorporating these new agents into their guidelines for management of prostate cancer. ☐