Eleven-year Management of Prostate Cancer Patients on Active Surveillance: What have We Learned?

Abstract

Cristina Marenghi and Maria Francesca Alvisi contributed equally to this work as co-first authors. Nicola Nicolai and Riccardo Valdagni contributed equally to this work. ABSTRACT Purpose:To evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification. Methods: In 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0.2 ng/mL/cm 3 (PRIAS). Switching to active treatment was advised for a worsening of GPS, increased positive cores, or PSA doubling time <3 years. Active treatment-free survival (ATFS) was assessed using the Kaplan-Meier method. Factors associated with ATFS were evaluated with a multivariate Cox proportional hazards model. Results: A total of 818 patients were included: 200 in SAINT, 530 in PRIAS, and 88 in personalized AS monitoring. Active treatment-free survival was 50% after a median follow-up of 60 months. A total of 404/818 patients (49.4%) discontinued AS: 274 for biopsy-related reclassification, 121/404 (30%) for off-protocol reasons, 9/404 (2.2%) because of anxiety. Biopsy reclassification was associated with PSA density (hazard ratio [HR] 1.8), maximum percentage of core involvement (HR 1.5), positive cores at diagnostic biopsy (HR 1.6), older age (HR 1.5), and prostate volume (HR 0.6) (all p<0.01). Patients from SAINT were significantly more likely to discontinue AS than were the patients from PRIAS (HR 1.65, p<0.0001). Conclusions: Five years after diagnosis, 50% of patients with early PCa were spared from active treatment. Wide inclusion criteria are associated with lower ATFS. However, at preliminary analysis, this does not seem to affect the probability of unfavorable pathology.

Active surveillance for prostate cancer: a systematic review of contemporary worldwide practices

“…Full-text screening was carried out on 36 articles, of which 23 were excluded, rendering 13 articles included ( Figure 1 —PRISMA diagram) each describing a unique AS cohort. Of the 13 included cohort studies ( 10 - 22 ), 6 took place in North America ( 10 - 12 , 14 , 17 , 21 ), 5 in Europe ( 15 , 16 , 18 , 20 , 22 ), 1 worldwide ( 13 ) and 1 in Australia ( 19 ).…”

“…All cohorts agreed eligibility for AS meant clinically localised PC, with half of the cohorts using T2a or less, two [John Hopkins ( 11 ) and Goteborg ( 20 )] opting to follow the Epstein criteria of T1c (in at least one arm of their cohort study). At the other end of the spectrum, three studies also included patients with T2b [(St Vincent’s, Australia ( 19 ), Canary PASS ( 21 ) and Milan ( 22 )] and two cohorts men diagnosed with T2c disease [Canary PASS ( 21 ) and Milan ( 22 )].…”

“…PSA density was featured in five cohorts ( 11 , 13 , 20 - 22 ). However, there was no consensus, with Milan ( 22 ) and PRIAS ( 13 ) suggesting a cut off of 0.2 and John Hopkins ( 11 ), Goteborg ( 20 ) and Canary PASS ( 21 ) opting for a more conservative 0.15.…”

Making Active Surveillance a path towards health promotion: A qualitative study on prostate cancer patients’ perceptions of health promotion during Active Surveillance

“…No first-year AS patients were included because of their "limited" experience of being on AS. Moreover, their experiences are likely to be influenced by feelings and perceptions related to waiting for the first-year re-biopsy, an important turning point where around one third of diseases are reclassified (Bul et al, 2013;Macleod et al, 2017;Marenghi et al, 2017).…”

“…To safely avoid treatment and the related side effects (Tosoian, Carter, Lepor, & Loeb, ), and to preserve patients’ quality of life (Bellardita et al, ; Soloway et al, ; Venderbos et al, ), monitoring strategies such as Active Surveillance started in many countries worldwide and gained popularity in the recent years (Loeb et al, ). Indeed, according to major guidelines, low‐risk diseases do not necessarily require radical treatments (Bul et al, ; Klotz, ; Marenghi et al, ) and give patients the possibility to choose between radical treatments (radiotherapy, brachytherapy and prostatectomy) and Active Surveillance (AS).…”