ASCO GU 2017: What ProtecT Tells Us About Active Surveillance - Session Highlights

Orlando, Florida USA ( In this session, Dr. Hamdy presented the results of the prostate testing for cancer and treatment (ProtecT) trial. ProtecT is the largest randomized trial to date comparing active monitoring, surgery, and radiotherapy for PSA-detected localized prostate cancer. The initial screening included 82,429 patients from 2,965 centers and spanned from 1999-2008. The primary endpoint was 10-year disease specific survival. Secondary outcome measures were all-cause mortality, progression, and patient-reported outcome measures (PROMs).

Patients were randomized to active monitoring, surgery, or radiotherapy. Active monitoring was a surveillance program in which men were followed with regular PSA testing and re-evaluation of their disease. The stated purpose of active monitoring was to avoid unnecessary treatment while maintaining the “window of opportunity” for cure if treatment became necessary. Trigger for intervention included PSA kinetics (more than 50% over 12 months), symptoms, changes in DRE, and patient/physician anxiety. Surgery was radical prostatectomy. Radiotherapy was comprised of androgen deprivation and 74 Gray of 3D conformal external beam radiation therapy.

Of the 82,429 patients who were screened with PSA, 2,664 eligible cases were identified. Of these approximately one-third (n=1,021) declined randomization. The remaining 1,643 men were randomized to active monitoring (n=545), surgery (n=533), or radiotherapy (n=545). An intention-to-treat analysis was employed.

Movement from active monitoring to treatment was observed in more than 50% of men at 10 years. Interestingly, approximately 80% of men on active monitoring did not demonstrate any clinical progression. A large number of men (44%) avoided treatment while on active monitoring. At 10 years, prostate cancer specific mortality was 1% and all-cause mortality was 12%. There was no difference among the three arms. With regard to PROMs, both urinary function and erectile function were worsened by treatment. However, Dr. Hamdy highlighted that all men lost erectile function regardless of the group to which they were randomized and suggested that men be counseled regarding the general effects of aging on erectile function. No differences in general quality of life, anxiety, or depression were noted among the groups.

The number needed to treat (NNT) to prevent one man from developing metastasis from prostate cancer was 27 for radical prostatectomy and 33 for radiation therapy. The NNT to prevent one man from clinical progression was 9 for both surgery and radiotherapy.

Dr. Hamdy concluded with learning points from ProtecT. The trade-off between oncological outcomes (progression) and side-effects of treatment is critical to consider. Active surveillance is valid option in low and select intermediate risk disease. He suggested that risk stratification at biopsy is inaccurate and may be improved by pre-biopsy imaging and targeting. Lastly, genomic diversity remains the “Achilles heel” of appropriate risk assessment. The ability to distinguish lethal from non-lethal prostate cancers will produce major paradigm changes as the field moves forward.

1. Hamdy et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. NEJM 2016; 375: 1415-1424
2. Donovan et al. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. NEJM 2016; 375: 1425-1437

Presented By: Freddie C. Hamdy, MD, FRCS, FMedSci, University of Oxford

Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA