Outcomes of Active Surveillance for Clinically Localized Prostate Cancer in the Prospective, Multi-Institutional Canary PASS Cohort

Newcomb, Lisa F.; Thompson, Ian M.; Boyer, Hilary; Brooks, James D.; Carroll, Peter R.; Cooperberg, Matthew R.; Dash, Atreya; Ellis, William; Fazli, Ladan; Feng, Ziding; Gleave, Martin; Kunju, Priya; Lance, Raymond S.; McKenney, Jesse K.; Meng, Maxwell V.; Nicolas, Marlo; Sanda, Martin G.; Simko, Jeffry P.; So, Alan; Tretiakova, Maria; Troyer, Dean A.; True, Lawrence D.; Vakar-López, Funda; Virgin, Jeff; Wagner, Andrew A.; Wei, John T.; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.

doi:10.1016/j.juro.2015.08.087

Cited by 132 publications

(128 citation statements)

References 28 publications

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“…Because of sampling errors in biopsies, approximately 40% of Gleason score 3+3 = 6 cancers on pre-operative biopsy are found to be ≥ 7 at the time of radical prostatectomy [31]. Under grading and under staging are significant challenges when selecting men with apparent low risk CaP for active surveillance, and likely account for significant rates of adverse reclassification for men while on surveillance [32]. The potential for MUC1 to predict adverse reclassification has been suggested by a demonstration that MUC1 expression independently predicted upstaging and upgrading in low risk prostate cancers incidentally discovered at the time of transurethral resection of the prostate.…”

Section: Discussionmentioning

confidence: 99%

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study

et al. 2016

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BackgroundThe uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters.Material and MethodsMUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test.ResultsThe presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03–1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS).ConclusionIn our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

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Section: Discussionmentioning

confidence: 99%

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study

et al. 2016

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“…Eligibility criteria include clinical stage ≤T2 disease and either a 10-core biopsy ≤1 year before enrollment or ≥2 biopsies with at least one ≤1 year before enrollment (3). Men are monitored with PSA tests every 3 months, DRE every 6 months, and biopsies 6–12, 24, 48, and 72 months after enrollment.…”

Section: Methodsmentioning

confidence: 99%

“…Several studies are ongoing in North America (3–6) and Europe (7) to learn about the outcomes of AS, but they involve different populations, follow-up durations, inclusion criteria, surveillance protocols, and definitions of progression that lead to treatment referral.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Biopsy Upgrading in Four Prostate Cancer Active Surveillance Cohorts

et al. 2017

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Background Active surveillance (AS) is increasingly accepted for managing low-risk prostate cancer, yet there is no consensus about implementation. The lack of consensus is due in part to uncertainty about risks of disease progression, which have not been systematically compared or integrated across AS studies with variable surveillance protocols and dropout to treatment. Objective To (1) compare risks of upgrading from Gleason score (GS) ≤6 to ≥7 across AS studies after accounting for differences in surveillance intervals and competing treatments and (2) evaluate tradeoffs of more vs less frequent biopsies. Design Joint statistical model of longitudinal prostate-specific antigen (PSA) levels and risks of biopsy upgrading. Setting Johns Hopkins University (JHU), Canary Prostate Active Surveillance Study (PASS), University of California San Francisco (UCSF), and University of Toronto (UT) AS studies. Patients 2,576 men aged 40–79 years diagnosed with GS ≤6 and clinical stage ≤T2 prostate cancer enrolled in 1995–2014. Measurements PSA levels and biopsy GS. Results After accounting for variable surveillance intervals and competing treatment, estimated risks of biopsy upgrading in PASS and UT were similar, but UCSF was higher and JHU lower. All cohorts produced a delay of 3–5 months in detecting upgrading under biennial biopsies starting after a first confirmatory biopsy relative to annual biopsies. Limitations The model does not account for possible biopsy GS misclassification. Conclusions Men in different AS studies exhibit different risks of biopsy upgrading after accounting for variable surveillance protocols and competing treatments. Nonetheless, despite these differences, the consequences of more versus less frequent biopsies appear to be similar across cohorts. Biennial biopsies appear to be an acceptable alternative to annual biopsies. Funding Source National Cancer Institute and others.

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“…1,2 However, up to one third of men will discontinue AS in favor of definitive treatment within 5 years. 3,4 Although most men who later choose treatment do so in the context of clinical progression, 5 psychosocial factors may nonetheless drive patients under AS toward definitive treatment. 6,7 Whereas a decision to discontinue AS may be driven by disease progression, 8 the impact of psychosocial constructs such as anxiety, social support, and participation in medical decision-making (PDM) on the course of AS has received little attention in literature to date.…”

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The Influence of Psychosocial Constructs on the Adherence to Active Surveillance for Localized Prostate Cancer in a Prospective, Population-based Cohort

Lang

Tyson

Alvarez

et al. 2017

Urology

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OBJECTIVE To evaluate the influence of psychosocial factors such as prostate cancer (PCa) anxiety, social support, participation in medical decision-making (PDM), and educational level on patient decisions to discontinue PCa active surveillance (AS) in the absence of disease progression. METHODS The Comparative Effectiveness Analysis of Surgery and Radiation study is a prospective, population-based cohort study of men with localized PCa diagnosed in 2011–2012. PCa anxiety, social support, PDM, educational level, and patient reasons for discontinuing AS were assessed through patient surveys. A Cox proportional hazards model examined the relationship between psychosocial variables and time to discontinuation of AS. RESULTS Of 531 patients on AS, 165 (30.9%) underwent treatment after median follow-up of 37 months. Whereas 69% of patients cited only medical reasons for discontinuing AS, 31% cited at least 1 personal reason, and 8% cited personal reasons only. Patients with some college education discontinued AS significantly earlier (hazard ratio: 2.0, 95% confidence interval: 1.2, 3.2) than patients with less education. PCa anxiety, social support, and PDM were not associated with seeking treatment. CONCLUSION We found that 31% of men who choose AS for PCa discontinue AS within 3 years. Eight percent of men who sought treatment did so in the absence of disease progression. Education, but not psychosocial factors, seems to influence definitive treatment-seeking. Future research is needed to understand how factors unrelated to disease severity influence treatment decisions among patients on AS to identify opportunities to improve adherence to AS.

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Outcomes of Active Surveillance for Clinically Localized Prostate Cancer in the Prospective, Multi-Institutional Canary PASS Cohort

Cited by 132 publications

References 28 publications

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study

Comparative Analysis of Biopsy Upgrading in Four Prostate Cancer Active Surveillance Cohorts

The Influence of Psychosocial Constructs on the Adherence to Active Surveillance for Localized Prostate Cancer in a Prospective, Population-based Cohort

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