Active Surveillance for Prostate Cancer: A Systematic Review of the Literature
Department of Urology, University of California-Davis Medical Center, Sacramento, CA, USA. European Urology
(Impact Factor: 13.94).
06/2012; 62(6). DOI: 10.1016/j.eururo.2012.05.072
CONTEXT: Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions. OBJECTIVE: To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs. EVIDENCE ACQUISITION: A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention. EVIDENCE SYNTHESIS: Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27-100%) or prostate-specific antigen doubling time <3 yr (13-48%), while 7-13% are treated with no evidence of progression. Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time. CONCLUSIONS: AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount.
Available from: Charlotte Kweldam
- "For instance, the Steyerberg nomogram incorporates number of positive biopsies, total cancer length (mm), and total “normal” tissue length (mm) to predict indolent disease on radical prostatectomy . In addition, most active surveillance protocols are delimitated by the number of positive biopsies and/or a measure of tumor extent per biopsy [31, 32]. "
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ABSTRACT: Prostate cancer is diverse in clinical presentation, histopathological tumor growth patterns, and survival. Therefore, individual assessment of a tumor's aggressive potential is crucial for clinical decision-making in men with prostate cancer. To date a large number of prognostic markers for prostate cancer have been described, most of them based on radical prostatectomy specimens. However, in order to affect clinical decision-making, validation of respective markers in pretreatment diagnostic needle-biopsies is essential. Here, we discuss established and promising histopathological and molecular parameters in diagnostic needle-biopsies.
Available from: PubMed Central
- "Active surveillance (AS) of prostate cancer (PCa) with delayed intervention represents an attractive management option, as it delays and possibly avoids the morbidity and potential mortality associated with radical prostatectomy (RP) or various radiotherapy alternatives –. Despite the promising results of several major surveillance cohorts, and its 10-year disease specific survival of 97–100% , the estimation of whether patients should be actively treated for low-risk PCa remains controversial, as multiple studies have reported that a considerable proportion of men qualifying for AS have aggressive tumor features at the time of RP –. Therefore, a well-established selection criterion among the PCa patients is important. "
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Active surveillance (AS) is a promising option for patients with low-risk prostate cancer (PCa), however current criteria could not select the patients correctly, many patients who fulfilled recent AS criteria experienced pathological Gleason score upgrade (PGU) after radical prostatectomy (RP). In this study, we aimed to develop an accurate model for predicting PGU among low-risk PCa patients by using exome genotyping.
We genotyped 242,221 single nucleotide polymorphisms (SNP)s on a custom HumanExome BeadChip v1.0 (Illuminam Inc.) in blood DNA from 257 low risk PCa patients (PSA <10 ng/ml, biopsy Gleason score (GS) ≤6 and clinical stage ≤T2a) who underwent radical prostatectomy. Genetic data were analyzed using an unconditional logistic regression to calculate an odds ratio as an estimate of relative risk of PGU, which defined pathologic GS above 7. Among them, we selected persistent SNPs after multiple testing using FDR method, and we compared accuracies from the multivariate logistic model incorporating clinical factors between included and excluded selected SNP information.
After analysis of exome genotyping, 15 SNPs were significant to predict PGU in low risk PCa patients. Among them, one SNP – rs33999879 remained significant after multiple testing. When a multivariate model incorporating factors in Epstein definition – PSA density, biopsy GS, positive core number, tumor per core ratio and age was devised for the prediction of PGU, the predictive accuracy of the multivariate model was 78.4% (95%CI: 0.726–0.834). By addition the factor of rs33999879 in aforementioned multivariate model, the predictive accuracy was 82.9%, which was significantly increased (p = 0.0196).
The rs33999879 SNP is a predictor for PGU. The addition of genetic information from the exome sequencing effectively enhanced the predictive accuracy of the multivariate model to establish suitable active surveillance criteria.
Available from: Hironori Betsunoh
- "A validation of AS protocol should not be a surrogate endpoint, such as the analysis of the pathologic results of prostatectomy specimens, but should be a long-term outcome of a prospective cohort. According to the review of AS in the large prospective series, approximately one-third of patients were treated after a median surveillance of about 2.5 years because of histologic reclassification on biopsy or a PSA doubling time of less than 3 years, while some cases were treated with no evidence of progression
. The short- to mid-term estimated treatment-free survivals were reported as 62 to 72% at 5 years and at 43 to 62% at 10 years
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Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy.
Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined).
Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis.
Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.
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