Matthew R. Cooperberg, MD, MPH
It has been recognized that treatment outcomes for men with high-risk prostate cancer are widely variable. Endpoints, such as biochemical failure–free survival, distant metastasis–free survival, prostate cancer–specific survival, and even overall survival (OS), vary according to the high-risk characteristics the patient presents with at the time of diagnosis.
Managing the patient with high-risk, localized prostate cancer has been a challenge for urologists. These patients have less than positive outcomes when compared with other patients with more favorable clinical characteristics. The National Comprehensive Cancer Network and the American Urological Association define this patient as having an increased Gleason score (Gleason 8 to 10) and a PSA over 20 ng/ml.
In addition, these patients are characterized by “a clinical tumor stage greater than T2c in the case of the AUA system or T3a in the NCCN system,” said Matthew Cooperberg, MD, associate professor in the departments of Urology and Epidemiology & Biostatistics, Helen Diller Family Chair in Urology, University of California San Francisco. “I think there are many of us that would argue that the AUA or NCCN classifications are not a very good way to define high-risk disease because there’s a tremendous amount of prognostic heterogeneity within high-risk groups.”
Prostate cancer’s characteristic slow growth pattern and the potential toxicity of current treatments makes risk stratification of patients all the more important to clinicians and researchers. But how these patients should be stratified, in clinical practice and for research trials, is increasingly complex.
There are a number of risk prediction tools at the clinician’s disposal. An effective tool will be able to provide a prediction of a positive biopsy with or without a prior negative biopsy; prediction before surgery of pathologic outcomes; prediction before and after surgery of biochemical and clinical endpoints; prediction before radiotherapy of biochemical and clinical endpoints; and prediction of metastases and survival among patients with recurrent disease after primary treatment.1
Currently, the only risk assessment tool endorsed by the AUA is a 3-level classification described by D’Amico et al.2
This system uses PSA level (blood test), Gleason grade (microscopic appearance of the cancer cells), and T stage (size of the tumor on rectal exam and/or ultrasound) to group men as low-, intermediate-, or high-risk. There are significant limitations associated with this classification. Multivariable instruments such as a variety of nomograms and the CAPRA score are able to provide much more precise estimates of risk, and some have been well validated at this point. But with the emergence of prostate cancer biomarkers, it is hoped that validation of risk stratification tools will elucidate, for clinicians, which clinically based instruments to use and in which settings.
Standard of Care
The standard of care for the high-risk patient population is either combined radiation therapy with hormonal therapy or radical prostatectomy (RP) with pelvic lymph node dissection. Surgery in this patient group was historically avoided, potentially based on the perception of ostensibly higher complication rates associated with inferior functional and oncological outcomes. But that trend may be shifting according to emerging research.
Recent studies suggest that RP is not only appropriate for this population but also may be a more optimal initial treatment, given that many of these patients require multimodal therapy to manage their disease. The question about radiation versus surgery lies in the details, with treatment tailored to each patient. The decision is usually made after considering the patient’s overall health, life expectancy, and the disease risk, ie, PSA, tumor extent, and grade, said Cooperberg.
“If surgery is chosen, it should include lymph node dissection in high-risk disease. If radiation is the first treatment option, the next question to consider is external beam versus brachytherapy versus a combination and how much hormonal therapy should be given together with the radiation therapy,” Cooperberg said.