EAU 2017: Lessons from the ProtecT trial

London, England (UroToday.com) In this session, Professor Mottet discussed lessons learned from the ProtecT trial. He began by reviewing what we know about intervention for prostate cancer and survival. The SPCG-4 trial represented an epoch early in screening for prostate cancer as only 5% of the patients were screen detected and the mean PSA was 13 ng/ml. Patients were randomized to radical prostatectomy versus watchful waiting. Prostate cancer-specific death carried a relative risk of 0.56 (95% CI 0.41-0.77) in the prostatectomy arm relative to the watchful waiting arm. The PIVOT trial represented a different population. These were primarily screen detected cancers comprised of 40% low risk and 34% intermediate risk. The hazard ratio for overall survival for prostatectomy was 0.63 (95% CI 0.36-1.09, p = 0.09) relative to watchful waiting.

ProtecT contained mostly low risk patient (~70%) and demonstrated no difference in cancer-specific death between active monitoring (AM, 1.4%), radiation therapy (XRT, 0.7%), or radical prostatectomy (RP, 0.9%) (p = 0.48). Additionally, no differences were noted among groups for overall death (AM 10.8%, XRT 10.1%, RP 9.9%; p = 0.87).

Dr. Mottet’s first comment was that most patients were low and intermediate risk. It is not particularly surprising that differences were not noted in the low risk population. However, there was a population of intermediate risk patients. At present, the analysis of this patient population is unknown. He highlighted an ongoing RCT for high risk patients that is currently underway (SPCG-15).

Secondly, he commented that treatment techniques may have been outdated. Regarding surgery, there was no quality control and an exclusively open prostatectomy technique was utilized. For radiation, an old-fashioned technique (3D conformal therapy) was used and 3-6 months of ADT were administered. Thus, he was concerned for the generalizability of these results to modern cohorts.

Third, he noted that the active surveillance programs used in ProtecT did not involve repeat biopsy or include MRI. Further, there was initial under-evaluation as evidenced by 5/8 patients with Gleason 7 disease who died in the active monitoring arm and a 6% metastasis rate at 10 years. Thus, active monitoring was suboptimal in these patients, particularly for younger patients.

Dr. Mottet made three conclusions. First, randomized trials are key and feasible; however, this does not mean that they are easy to run. The ProtecT researchers are commended for putting this remarkable trial together. Second, better selection is needed between active monitoring and treatment for many screen-detected cancer patients. Systematic treatment is likely too much for most low risk and questionable for some intermediate risk. Lastly, given the increased metastatic rate in the active monitoring group, it will be important to continue to follow these patients over time to see if a survival benefit emerges.

Comment 1 – patients mainly low/intermediate risk

Higher risk groups need RCT (underway SPCG 15)
Functional outcomes – confirmed results

Surgery: adjuvant/salvage RX if T1 or pT2 PSA > 0.2
Radiotherapy: 3D conformal 74Gy + 3-6 moths ADT

Clinical progression – 2x metastases in AM group compared to intervention
Metastasis defined as M1a, M1b, or PSA > 100

Not active surveillance, it is monitoring

Active monitoring is suboptimal
Rationale for AS confirmed
Lower under-staging

Speaker(s): N. Mottet, St. Etienne, FR

Written By: Benjamin T. Ristau, MD, SUO Fellow, Fox Chase Cancer Center, Philadelphia, PA

at the #EAU17 - March 24-28, 2017- London, England