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Studies Suggest Radical Prostatectomy May Be Optimal in Men With High-Risk Prostate Cancer

Tony Berberabe, MPH
Published Online:5:52 PM, Thu December 3, 2015

The standard of care for this high-risk prostate cancer patient population is either combined radiation therapy with hormonal therapy or radical prostatectomy with pelvic lymph node dissection. Surgery has historically been avoided, possibly based on the perception of higher complication rates associated with inferior functional and oncological outcomes. However, that trend may be on the downswing according to emerging research.

Radical Prostatectomy High-Risk Prostate Cancer

Matthew R. Cooperberg, MD, MPH

Managing patients with high-risk, localized prostate cancer has historically presented a challenge for urologists. Endpoints such as biochemical failure–free survival, distant metastasis–free survival, prostate cancer–specific survival, and overall survival (OS) fluctuate according to high-risk characteristics patients present at the time of diagnosis.

 

Patients have less positive outcomes compared to patients with more favorable clinical characteristics. The National Comprehensive Cancer Network and the American Urological Association define these patients as having an increased Gleason score (Gleason 8 to 10) and a PSA over 20 ng/ml. 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, 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."

 

A combination of slow growth patterns in prostate cancer and possible toxicities of current treatments makes patient risk stratification that much more important to clinicians and researchers, though a definitive answer on how these patients should be stratified in clinical practice and research trials is complex. The only current risk assessment tool endorsed by the AUA is a 3-level classification described by D’Amico et al.2 The system employs 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. 

 

A hypothetically effective tool will be able to predict a positive biopsy with or without a prior negative biopsy, before surgery or pathologic outcomes, before and after surgery of biochemical and clinical endpoints, and predict metastases and survival among patients with recurrent disease after primary treatment.1 Multivariable instruments like a variety of nomograms and CAPRA score can provide much more precise estimates of risk, and some have been well validated at this point. 

 

With the emergence of biomarkers in prostate cancer, it is hoped that validation of risk stratification tools will elucidate, for clinicians, which instruments and methods to use in a variety of settings.

 

Standard of Care in High-Risk Prostate Cancer Patients

 

The standard of care for this high-risk prostate cancer patient population is either combined radiation therapy with hormonal therapy or radical prostatectomy (RP) with pelvic lymph node dissection. Surgery has historically been avoided, possibly based on the perception of higher complication rates associated with inferior functional and oncological outcomes. However, that trend may be on the downswing according to emerging research.

 

Recent studies suggest that RP may be a better initial treatment given 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, such as 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.

 

Recent trends suggest a shift away from radiation therapy and towards RP, said Stacy Loeb, MD, assistant professor of Urology and Population Health, New York University School of Medicine, NYU Langone Medical Center. 

 

"The shift may be attributed to multiple observational studies, rather than prospective, randomized studies," said Loeb. No randomized data comparing different therapy approaches have been reported. In addition, continence rates in patients who receive RP for seem to be unaffected. In many patients, a nerve-sparing procedure can be performed to improve the chances of potency without a significant negative impact on surgical margin rates.

 

Due to the absence of randomized trial data comparing these therapies, clinicians can only say that "surgery is better than watchful waiting and that hormonal therapy plus radiation is better than hormonal therapy alone," added Cooperberg. However, a growing body of evidence suggests a survival benefit associated with RP over external beam radiation therapy, specifically for high-risk disease.

 

"When we look at combined external beam radiation therapy with brachytherapy and long-term hormonal therapy, I think the gap narrows, but it does not close altogether," said Cooperberg. "So there does appear to be a benefit for surgery in this setting of high-risk disease."

 

Loeb said the other reason surgery may be initially preferred is that it is possible to give radiation and hormonal therapy at a later date, after the patient undergoes a RP.

 



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