AUA 2018: Treatment of High-Risk Prostate Cancer - Surgery

San Francisco, CA ( The comparative effectiveness of surgery and radiotherapy in the management of prostate cancer has been hotly debated for many years. However, as most patients with clinically localized disease have historically presented with low or intermediate risk disease, data to inform this comparison for patients with high risk disease has historically been lacking. Radiotherapy, combined with androgen deprivation therapy, has historically been predominantly employed for these patients. In a vigorous debate at the Society of Urologic Oncology meeting at the American Urologic Association Annual Meeting, Scott Eggener, MD and Alberto Bossi, MD debated the merits of surgery and radiotherapy, respectively, for patients with high-risk localized disease.

Eggener began by describing the rationale for surgery in these patients. He noted that historical data from Memorial Sloan Kettering has demonstrated that a subset of men (ranging from 41-74%) with high-risk disease may be cured with surgery alone.

Before presenting any comparative data, Eggener described recent data from Weiner et al. utilizing the National Cancer Database which demonstrated that the utilization of radical prostatectomy is on the rise in patients with high-risk prostate cancer while utilization of radiotherapy is falling. He then highlighted the importance of focusing on clinically meaningful outcomes including metastasis-free survival and prostate cancer specific survival.

Acknowledging that the available data is limited to observational studies, Eggener presented “at least” 11 studies supporting the assertion that surgery is superior to radiation for high-risk prostate cancer. He then went on to highlight two of these manuscripts. The first, from Memorial Sloan Kettering, was a blinded analysis of 2380 patients with cT1c – cT3b. Assessing metastases and death from prostate cancer, the authors demonstrated that patients had better outcomes following radical prostatectomy compared to IMRT (56% of whom also received ADT). The magnitude of effect was large (65%, HR=0.35) and robust to numerous sensitivity analyses accounting for nomogram risk, age, treatment year; NCCN risk category; and PSA, stage and Gleason score. Notably, the differential, beneficial effect of surgery over radiotherapy was largest among patients with high-risk disease (7.8% differential effect) as compared to those with intermediate risk disease (3.3%) or low risk disease (1.9%). However, this analysis failed to account for disease burden. In contrast, the second highlighted analysis from the CaPSURE dataset was able to account for disease volume among many other clinical variables using both the Kattan nomogram and the CAPRA score. In a generalizable cohort, cancer-specific survival was superior for patients undergoing surgery. Again, the greatest benefit to surgery was found among patients with the highest risk disease.

He then transitioned to two recently published manuscripts. In the Swedish National Dataset, the authors found no significant difference in the risk of metastases for patients with NCCN high-risk disease (HR 1.14, 95% CI 0.96-1.36). In addition to their primary analysis, Robinson et al. present an updated literature review. Among 16 identified studies comparing surgery and radiotherapy, they identified 11 showing a cancer-specific mortality benefit to surgery, 5 which showed no difference, and none of which showed a benefit to radiotherapy.

Finally, Eggener moved on to the first study to demonstrate a benefit of radiotherapy- based approaches in high risk prostate cancer. Recently published by Kishan et al., this is a multi-institutional analysis of 1800 patients with high grade, clinically localized prostate cancer. Patients who received trimodal brachytherapy, external beam radiotherapy and androgen deprivation had lower rates of 5-year metastases and cancer-specific mortality than patients who underwent radical prostatectomy (with variable use of postoperative radiotherapy) or those who underwent EBRT with ADT. Dr. Eggener then noted that the radiotherapy literature has failed to demonstrate a survival benefit to the addition of brachytherapy to EBRT in a number of randomized controlled trials. Therefore, the differences seen in the Kishan study require further validation.

Finally, Eggener highlighted future directions including neoadjuvant chemotherapy and androgen deprivation therapy or neoadjuvant combined androgen blockage prior to radical prostatectomy. In closing, he concluded that, based on best-available data in 2018, “surgery appears to be oncologically superior to radiation for the treatment of clinically-localized high-risk prostate cancer.”

Presented by: Scott Eggener, MD

Read the Opposing Viewpoint: Treatment of High-Risk Prostate Cancer - Radiation

Written by: Christopher J.D. Wallis, Urology Resident, University of Toronto @WallisCJD at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA