The debate between surgery and radiation therapy in patients with high-risk prostate cancer is fierce and lacks prospective, randomized evidence. A meta-analysis of 13 retrospective multivariable analyses with propensity scoring demonstrated 1.5-2.5 higher likelihood of prostate cancer-specific mortality for patients who have radiotherapy over surgery. Moreover, the hazard ratio of overall survival is 1.5 for patients undergoing radiation therapy compared to surgery. These data must be understood through the lens of retrospective analyses with undoubted selection biases despite best efforts to control through statistical manipulation.
Dr. Evans went into detail regarding four specific areas of surgery for high-risk prostate cancer. First, with regard to nerve-sparing: can the nerves be spared in patients with high-risk disease? Unfortunately, MRI has not been reliable in determining whether nerves can be safely spared. In contrast, some evidence does support the use of intraoperative frozen section of the neurovascular bundle can be useful in helping to choose appropriate nerve-sparing candidates.
Second, the goals of lymphadenectomy were discussed. Overall, the objective remains to identify patients with metastatic disease. The number of nodes is informative and can provide guidance with regard to adjuvant therapy. The possibility of cure, on the other hand, is uncertain. In fact, there is no evidence that removing more nodes leads directly to improved survival. Moreover, the cost is roughly twice the lymphocele rate and twice the number of overall complications. So, the risks and benefits must be considered on a case by case basis.
Third, Dr. Evans discussed adjuvant radiation therapy. In the SWOG study, a benefit was shown for adjuvant radiation in terms of metastasis-free survival (57% vs. 46%). However, patients with pT3a disease and negative margins were lumped into this analysis. Given that roughly 50% of patients will be overtreated with adjuvant radiation therapy and that there is a resulting doubling of quality of life detriments, Dr. Evans prefers not to recommend adjuvant radiation in pT3a patients with negative surgical margins.
Lastly, he briefly discussed BRCA mutations and treatment decisions in high-risk prostate cancer. Interestingly, approximately 12% harbor DNA-repair gene mutation. For patients who undergo surgery, no difference in overall survival outcomes were observed stratified by presence or absence of BRCA mutations. In contrast, for patients receiving radiation those who were BRCA positive had worse outcomes relative to BRCA negative patients. These findings are at least hypothesis-generating.
Presented by: C. Evans
Written by: Benjamin T. Ristau, MD, SUO Fellow, Fox Chase Cancer Center, Philadelphia, PA
at the #EAU17 -March 24-28, 2017- London, England