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Can contemporary patients with biopsy Gleason score 3+4 be eligible for active surveillance?

ABSTRACT: We analyzed whether expansion of existing active surveillance (AS) protocols to include men with biopsy Gleason score (GS) 3+4 prostate cancer (PCa) would significantly alter pathologic and biochemical outcomes of potential candidates of AS.Among patients who underwent radical prostatectomy at our center between 2006 and 2013, we identified 577 patients (group A) who preoperatively fulfilled at least one of 6 different AS criteria. Also, we identified 217 patients (group B) with biopsy GS 3+4 but fulfilled non-GS criteria from at least one of 6 AS criteria. Designating group C as expanded group incorporating all patients in group A and B, we compared risk of unfavorable disease (pathologic GS ≥ 4+3 and/or pathologic T stage ≥ pT3a) and biochemical recurrence (BCR)-free survival between groups.Rates of unfavorable disease were not significantly different between patients of group A and C who met AS criteria from 5 institutions (all p>0.05), not including University of Toronto (p < 0.001). Also BCR-free survivals were not significantly different between patients in group A and C meeting each of 6 AS criteria (all p > 0.05). Among group B, PSAD > 0.15 ng/mL/cm3 (p = 0.011) and tumor length of biopsy GS 3+4 core > 4 mm (p = 0.007) were significant predictors of unfavorable disease. When these two criteria were newly applied in defining group B, rates of unfavorable disease in group A and B was 15.6% and 14.7%, respectively (p = 0.886).Overall rate of pathologically aggressive PCa harbored by potential candidates for AS may not be increased significantly with expansion of criteria to biopsy GS 3+4 under most contemporary AS protocols. PSAD and tumor length of biopsy GS 3+4 core may be useful predictors of more aggressive disease among potential candidates for AS with biopsy GS 3+4.

SUBMITTER: Kwon O

PROVIDER: S-EPMC4182658 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Project description:BackgroundSeveral active surveillance (AS) criteria have been established to screen insignificant prostate cancer (insigPCa, defined as organ confined, low grade and small volume tumors confirmed by postoperative pathology). However, their comparative diagnostic performance varies. The aim of this study was to compare the diagnostic accuracy of contemporary AS criteria and validate the absolute diagnostic odds ratio (DOR) of optimal AS criteria.MethodsFirst, we searched Pubmed and performed a Bayesian network meta-analysis (NMA) to compare the diagnostic accuracy of contemporary AS criteria and obtained a relative ranking. Then, we searched Pubmed again to perform another meta-analysis to validate the absolute DOR of the top-ranked AS criteria derived from the NMA with two endpoints: insigPCa and favorable disease (defined as organ confined, low grade tumors). Subgroup and meta-regression analyses were conducted to identify any potential heterogeneity in the results. Publication bias was evaluated.ResultsSeven eligible retrospective studies with 3,336 participants were identified for the NMA. The diagnostic accuracy of AS criteria ranked from best to worst, was as follows: Epstein Criteria (EC), Yonsei criteria, Prostate Cancer Research International: Active Surveillance (PRIAS), University of Miami (UM), University of California-San Francisco (UCSF), Memorial Sloan-Kettering Cancer Center (MSKCC), and University of Toronto (UT). I2 = 50.5%, and sensitivity analysis with different insigPCa definitions supported the robustness of the results. In the subsequent meta-analysis of DOR of EC, insigPCa and favorable disease were identified as endpoints in ten and twenty-two studies, respectively. The pooled DOR for insigPCa and favorable disease were 0.44 (95%CI, 0.31-0.58) and 0.66 (95%CI, 0.61-0.71), respectively. According to a subgroup analysis, the DOR for favorable disease was significantly higher in US institutions than that in other regions. No significant heterogeneity or evidence of publication bias was identified.ConclusionsAmong the seven AS criteria evaluated in this study, EC was optimal for positively identifying insigPCa patients. The pooled diagnostic accuracy of EC was 0.44 for insigPCa and 0.66 when a more liberal endpoint, favorable disease, was used.Systematic review registration[https://www.crd.york.ac.uk/prospero/], PROSPERO [CRD42020157048].

Project description:ObjectiveTo develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted risks to create risk-based personalised biopsy schedules as an alternative to one-size-fits-all schedules (e.g. annually). Furthermore, to assist patients and doctors in making shared decisions on biopsy schedules, by providing them quantitative estimates of the burden and benefit of opting for personalised vs any other schedule in AS. Lastly, to externally validate our model and implement it along with personalised schedules in a ready to use web-application.Patients and methodsRepeat prostate-specific antigen (PSA) measurements, timing and results of previous biopsies, and age at baseline from the world's largest AS study, Prostate Cancer Research International Active Surveillance (PRIAS; 7813 patients, 1134 experienced upgrading). We fitted a Bayesian joint model for time-to-event and longitudinal data to this dataset. We then validated our model externally in the largest six AS cohorts of the Movember Foundation's third Global Action Plan (GAP3) database (>20 000 patients, 27 centres worldwide). Using the model predicted upgrading risks; we scheduled biopsies whenever a patient's upgrading risk was above a certain threshold. To assist patients/doctors in the choice of this threshold, and to compare the resulting personalised schedule with currently practiced schedules, along with the timing and the total number of biopsies (burden) planned, for each schedule we provided them with the time delay expected in detecting upgrading (shorter is better).ResultsThe cause-specific cumulative upgrading risk at the 5-year follow-up was 35% in PRIAS, and at most 50% in the GAP3 cohorts. In the PRIAS-based model, PSA velocity was a stronger predictor of upgrading (hazard ratio [HR] 2.47, 95% confidence interval [CI] 1.93-2.99) than the PSA level (HR 0.99, 95% CI 0.89-1.11). Our model had a moderate area under the receiver operating characteristic curve (0.6-0.7) in the validation cohorts. The prediction error was moderate (0.1-0.2) in theGAP3 cohorts where the impact of the PSA level and velocity on upgrading risk was similar to PRIAS, but large (0.2-0.3) otherwise. Our model required re-calibration of baseline upgrading risk in the validation cohorts. We implemented the validated models and the methodology for personalised schedules in a web-application (http://tiny.cc/biopsy).ConclusionsWe successfully developed and validated a model for predicting upgrading risk, and providing risk-based personalised biopsy decisions in AS of prostate cancer. Personalised prostate biopsies are a novel alternative to fixed one-size-fits-all schedules, which may help to reduce unnecessary prostate biopsies, while maintaining cancer control. The model and schedules made available via a web-application enable shared decision-making on biopsy schedules by comparing fixed and personalised schedules on total biopsies and expected time delay in detecting upgrading.

Project description:Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group.To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data.Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions.Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores.In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death.The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

Project description:Background and objectivesThe general rule that every active malignancy is an absolute contraindication for kidney transplantation is challenged by kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. Interdisciplinary treatment teams therefore often face the challenge of balancing the benefits of early kidney transplantation and the risk of metastatic progression. Hence, we compared the quality-adjusted life expectancy of different management strategies in kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup.Design, setting, participants, & measurementsA discrete event simulation model was developed on the basis of a systematic literature search, clinical guidelines, and expert opinion. After model validation and calibration, we simulated four management strategies in a hypothetical cohort of 100,000 patients: Definitive treatment (surgery or radiation therapy) and listing after a waiting period of 2 years, definitive treatment and immediate listing, active surveillance and listing after a waiting period of 2 years, and active surveillance and immediate listing. Individual patient results (quality-adjusted life years; QALYs) were aggregated into strategy-specific means (± SEs).ResultsActive surveillance and immediate listing yielded the highest amount of quality-adjusted life expectancy (6.97 ± 0.01 QALYs) followed by definitive treatment and immediate listing (6.75 ± 0.01 QALYs). These two strategies involving immediate listing not only outperformed those incorporating a waiting period of 2 years (definitive treatment: 6.32 ± 0.01 QALYs; active surveillance: 6.59 ± 0.01 QALYs) but also yielded a higher proportion of successfully performed transplantations (72% and 74% versus 56% and 59%), with less time on hemodialysis on average (4.02 and 3.81 years versus 4.80 and 4.65 years).ConclusionsAmong kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup, the active surveillance and immediate listing strategy outperformed the alternative management strategies from a quality of life expectancy perspective, followed by definitive treatment and immediate listing.

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Can contemporary patients with biopsy Gleason score 3+4 be eligible for active surveillance?

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