Super active surveillance for low-risk prostate cancer | Opinion: No

Prostate cancer (PCa) is diagnosed in over 170,000 men in the United States each year (1). While this makes PCa one of the most common solid malignancies in men, the mortality is low and most men die from unrelated causes (1). In fact, almost half of men with screening detected and localized PCa are considered candidates for deferred treatment or active surveillance (AS) (2). To decrease the morbidity associated with definitive therapy, many providers recommend AS for those with very-low (VLR), low risk (LR) disease and in selected favorable, intermediate risk (IR) PCa (3-5). The use of AS has been steadily increasing and is supported by large cohort studies showing 98-100% PCa specific survival rates (6, 7). While the recommended follow-up for AS varies, safety is predicated on close surveillance with predefined thresholds for treatment based on identification of cancer progression yet still curable disease. In the largest published AS cohort of 993 men with median follow-up of 6.4 years, 10-year cancer specific survival (CSS) was 98.1%. However, 27% of these patients ultimately underwent surgery for indications ranging from prostate specific antigen (PSA) progression, biopsy Gleason score progression or patient preference. While this cohort included mostly younger men with LR disease (Age <70, cT1/T2a disease, PSA <10ng/ml), they also included patients older than 70 with Gleason 3+4=7 or lower disease, such that 20% had IR (6). A separate analysis of this cohort by Musunuru et al. showed that while only 3% of patients developed metastases, metastasis free survival (MFS) was significantly lower in the IR as compared to the LR group (84% vs 95%, p=0.001) (8). Another separate cohort analysis by Yamamoto et al. showed a significantly higher risk of 15-year PCa mortality (PCM) for higher Gleason score disease (HR of 4.0 for Gleason 3+4=7 vs Gleason 3+3=6 and HR 10.5 for Gleason 4+3=7 vs Gleason 3+3=6) (9). The PROTECT trial randomized 1643 patients with localized PCa into AS (n=545), definitive treatment with radical prostatectomy (RP; n=553) or radiation therapy (RT; n=545). There was no difference in PCM amongst the 3 groups (p=0.48), however, of those 17 patients who passed away, 8 were in the AS group (5/8 with IR disease), 5 in the RP group and 4 in the RT group. The rate of disease progression and development of metastases was significantly higher in the AS group as compared to RP or RT (112 vs 46 vs 46 men, respectively; p<0.001) (10). Despite a certain subset of patients who seem to do worse on AS, concerns with morbidity from definitive treatment have led experts to recommend a broadening of the indications for AS and to include selected patients with low volume IR disease (3, 5, 11, 12). As the indications for AS expand, certain patients may wish to be even more “active” in their surveillance. In 2018, Bloom et DiffereNce Of OpiNiON Vol. 45 (2): 215-219, March April, 2019