PURPOSE Comparative efficacy research performed using population registries can be subject to significant bias. There is an absence of objective data demonstrating factors that can sufficiently reduce bias and provide accurate results. METHODS MEDLINE was searched from January 2000 to October 2016 for observational studies comparing two treatment regimens for any diagnosis of cancer, using SEER, SEER-Medicare, or the National Cancer Database. Reporting quality and statistical methods were assessed using components of the STROBE criteria. Randomized trials comparing the same treatment regimens were identified. Primary outcome was correlation between survival hazard ratio (HR) estimates provided by the observational studies and randomized trials. Secondary outcomes included agreement between matched pairs and predictors of agreement. RESULTS Of 3,657 studies reviewed, 350 treatment comparisons met eligibility criteria and were matched to 121 randomized trials. There was no significant correlation between the HR estimates reported by observational studies and randomized trials (concordance correlation coefficient, 0.083; 95% CI, −0.068 to 0.230). Forty percent of matched studies were in agreement regarding treatment effects (κ, 0.037; 95% CI, −0.027 to 0.1), and 62% of the observational study HRs fell within the 95% CIs of the randomized trials. Cancer type, data source, reporting quality, adjustment for age, stage, or comorbidities, use of propensity weighting, instrumental variable or sensitivity analysis, and well-matched study population did not predict agreement. CONCLUSION We were unable to identify any modifiable factor present in population-based observational studies that improved agreement with randomized trials. There was no agreement beyond what is expected by chance, regardless of reporting quality or statistical rigor of the observational study. Future work is needed to identify reliable methods for conducting population-based comparative efficacy research.

The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials.

In a large independent radiotherapy cohort with long-term follow-up, we have validated the bRFS benefit of the proposed five-tier grade grouping system. Furthermore, we have demonstrated that the system is highly prognostic for DMFS and PCSS. Grade group 5 had markedly worse outcomes for all end points, and future work is necessary to improve outcomes in these patients.

No abstract

ObjectiveTo elucidate the functional erection rate after prostate stereotactic body radiotherapy (SBRT) and to develop a comprehensive prognostic model of outcomes after treatment. Patients and MethodsBetween 2008 and 2013, 373 consecutive men with localized prostate cancer were treated with SBRT at a single academic institution as part of a prospective clinical trial or prospective registry. Prospective longitudinal patient-reported healthrelated quality of life (HRQoL) data was collected using the Expanded Prostate Cancer Index Composite (EPIC)-26 instrument. Functional erections were strictly defined as 'firm enough for intercourse' according to EPIC-26. Detailed comorbidity data were also collected. Logistic regression models were used to predict 24-and 60-month functional erection rates. Observed erection rates after SBRT were compared with those after other radiation therapies (external beam radiation therapy [EBRT] and brachytherapy) using prospectively validated models. ResultsThe median (interquartile range) follow-up was 56 (37-73) months and the response rate at 2 years was 84%. For those with functional erections at baseline, 57% and 45% retained function at 24 and 60 months, respectively. On multivariable analysis for 24-month erectile function, significant variables included higher baseline sexual HRQoL (adjusted odds ratio [aOR] 1.55 per 10 points, 95% confidence interval [CI] 1.37-1.74; P < 0.001) and older age (aOR 0.66 per 10 years, 95% CI 0.43-1.00; P = 0.05). At 60 months, baseline HRQoL and age remained associated with erectile function, along with body mass index (aOR 0.45, 95% CI 0.26-0.78; P < 0.001). The 24-and 60-month models had excellent discrimination (c-index 0.81 and 0.84, respectively). Erection rates after SBRT were not statistically different from model-predicted rates after EBRT or brachytherapy for the whole cohort and the cohort with baseline erectile function. ConclusionsIntermediate-to long-term post-SBRT erectile function results are promising and not significantly different from other radiotherapy techniques. Clinicians can use our prognostic model to counsel patients regarding expected erectile function after SBRT.