Sharma, Vidit

AbstractBackgroundThe VESPER trial demonstrated improved progression‐free (PFS) and (preliminarily) overall survival (OS) with six cycles of neoadjuvant dose‐dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVACx6) versus four cycles of gemcitabine and cisplatin (GCx4) before radical cystectomy (RC) for muscle‐invasive bladder cancer (MIBC), but with increased toxicity. This study compares the cost‐effectiveness of these regimens.MethodsA cost‐effectiveness analysis of neoadjuvant ddMVACx6 and GCx4 was performed using a decision‐analytic Markov model with 5‐year, 10‐year, and lifetime horizons. Probabilities were derived from reported VESPER data. Utility values were obtained from the literature. Primary outcomes were effectiveness measured in quality‐adjusted life years (QALY) and incremental cost‐effectiveness ratio (ICER) with a willingness to pay threshold of $100,000 per QALY. One‐way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model.ResultsAt 5 years, ddMVACx6 improved QALYs by 0.30 at an additional cost of $16,100, rendering it cost‐effective relative to GCx4 (ICER: $53,284/QALY). Additionally, probabilistic sensitivity analysis found ddMVACx6 to be cost‐effective in 79% and 81% of microsimulations at10‐year and lifetime horizons, respectively. One‐way sensitivity analysis demonstrated a minimum difference in 5‐year progression of 0.9% and progression mortality of 0.7% between ddMVACx6 and GCx4 was necessary for ddMVACx6 to remain cost‐effective.ConclusionsNeoadjuvant ddMVACx6 was more cost‐effective than GCx4 for MIBC. These data, together with the improved PFS and (albeit preliminary) OS noted in VESPER, support use of this regimen in appropriate candidates for neoadjuvant chemotherapy before RC.Lay summary We performed a benefit‐to‐cost analysis using evidence from a randomized controlled trial that compared two different chemotherapy treatments before bladder removal for bladder cancer that had invaded into the bladder muscle. Despite being more expensive and having a greater likelihood of toxicity, six cycles of dose‐dense methotrexate, vinblastine, doxorubicin, and cisplatin was more cost‐effective (or had higher value) than four cycles of gemcitabine and cisplatin.

321 Background: KEYNOTE-564 demonstrated that adjuvant pembrolizumab after nephrectomy for high-risk clear cell renal cell carcinoma (RCC) decreased the risk of disease progression and – albeit with immature follow-up (2 years) – found a signal of improved overall survival as well. Herein, we used extrapolations from a Markov-model, accounting for the costs and toxicities of pembrolizumab relative to its efficacy, to investigate its utility at a population level. Methods: A decision-analytic Markov Model was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus placebo after nephrectomy for high risk RCC, using data from KEYNOTE-564 to inform model probabilities. Transition probabilities not found in KEYNOTE-564, in addition to utility values, were extracted from the literature. Base case analyses were conducted with 5-year and 15-year time horizons (using extrapolations from 2-year outcomes), and 3-week time cycles. Primary outcomes were Quality-adjusted life years (QALYs), 2021 US Medicare costs, and Incremental cost-effectiveness ratios (ICERs). The willingness-to-pay threshold was set at $100,000/QALY. One-way sensitivity analyses were used to identify cost-effectiveness thresholds of individual parameters while probabilistic sensitivity analyses with 100,000 Monte-Carlo simulations were used to simultaneously vary all model inputs. Results: Pembrolizumab was associated with higher QALYs and costs relative to placebo (Table). Pembrolizumab was not cost-effective at a 5-year time horizon but was cost-effective at 15 years and beyond. One-way sensitivity analysis noted that pembrolizumab became cost-effective at 5-years if: 1) its administration cost was less than $5,064 (base = $10,278) or 2) if the 5-year risk of progression was 18.8% higher in placebo vs pembrolizumab (base = 9%). Using pembrolizumab’s reported hazard ratio of 0.68 for progression from KEYNOTE-564, we estimated that pembrolizumab would be cost-effective at 5-years for all patients with a Mayo Progression Free Survival Score of 10 or higher. Probabilistic sensitivity analysis found that pembrolizumab was cost-effective for 29% and 58% of microsimulations at 5 and 15 years, respectively. Conclusions: At current prices, adjuvant pembrolizumab was not cost-effective for all trial patients at a population level at 5-years after treatment but may be cost-effective for time horizons over 15 years. Instead, adjuvant pembrolizumab was found to be cost-effective only for the highest risk subsets of RCC at 5-years. Longer term trial data of progression-free survival and overall survival are necessary to confirm these extrapolations.[Table: see text]

ABSTRACTBackgroundCongenital penile curvature (CPC) is corrected surgically by various corporoplasty or tunica albuginea plication techniques, but the optimal surgical approach is not well-defined.AimTo provide a comprehensive evaluation of the published literature pertaining to outcomes with penile plication and corporoplasty techniques for surgical management of CPC. To determine if plication or corporoplasty offers superior outcomes in surgical correction of CPC.MethodsA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist. The following databases were queried from inception to March 18, 2020 to search for studies describing surgical treatment of CPC: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.OutcomesObjective and subjective postoperative outcomes including penile straightening, shortening, penile sensory changes, and reoperation rates for both corporoplasty and tunica albuginea plication were summarized.ResultsFifty-five articles comprising 2,956 patients with CPC who underwent a plication procedure (n = 1,375) or corporoplasty (n = 1,580) were included. The definition of “treatment success” varied widely and most often involved subjective patient reporting (22 studies; 40%) or objective assessment (15 studies; 27%). We considered curvature correction to be satisfactory if there was self-reported patient satisfaction or residual curvature after correction of <20˚. Reported rates of successful straightening ranged from 75 to 100% and 73 to 100% for plication and corporoplasty, respectively. A comprehensive and accurate assessment of surgical outcomes for CPC correction, such as satisfactory penile straightening, reoperation rates, glans sensory changes, and other complications was limited by significant inter-study heterogeneity with respect to the reporting of treatment outcomes.Clinical ImplicationsWhile both plication and corporoplasty appear to be safe and effective options in the treatment of CPC, definitive conclusions cannot be drawn with respect to treatment superiority due to low-quality study design, methodology flaws, and significant heterogeneity in reporting.Strength & LimitationsThis report represents the most comprehensive review of CPC surgical management. However, there is a significant lack of standardization in the reporting of treatment outcomes for CPC, thereby limiting the reliability of the published data summarization encompassed by our review.ConclusionBoth plication and corporoplasty demonstrate high success rates and relatively low complication rates in the treatment of CPC, albeit with low-level evidence available in most research publications. Robust comparison of the surgical techniques used to correct CPC is limited by significant variation in reporting methods used in the literature.

Purpose of review Metastases directed therapy (MDT) is an increasingly utilized modality in patients with oligometastatic prostate cancer (OMPC) recurrence. The purpose of our review is to discuss the recent literature on the safety and oncologic outcomes of this treatment approach. Recent findings Metastases directed therapy, in particular, stereotactic body radiation therapy (SBRT) and salvage lymph node dissection (sLND), has shown promising efficacy in patients with OMPC. Many case series report favorable outcomes with MDT as compared to hormonal deprivation therapy alone or surveillance. Of the few case series investigating the use of MDT as part of a multimodality approach in castrate-resistant OMPC, more favorable outcomes in comparison to the use of systemic treatment alone are reported. Summary With the recent advances in imaging techniques, particularly molecular imaging, management of OMPC has progressed rapidly in the last few years. The feasibility and benefits of MDT in OMPC have been demonstrated in prospective and retrospective series. Further prospective studies investigating the role of MDT to define optimal patient subgroups and management strategies are warranted.

421 Background: Reported rates of adherence to post-radical cystectomy (RC) surveillance guidelines in real-world practice have been as low as 9%, in part reflecting a nihilistic view held by many of the value of routine follow-up. Indeed, conflicting data exist regarding the outcomes of patients with cancer recurrence detected by scheduled surveillance versus symptom-directed evaluation. Herein, we assessed comparative outcomes of patients with symptomatic recurrence (SR) versus asymptomatic recurrence (AR) after RC. Methods: We reviewed our Institutional Registry of RC patients to identify patients with cancer recurrence following RC. Presenting symptoms in the SR cohort included pain, constitutional symptoms, gastrointestinal symptoms, and hematuria/voiding symptoms, whereas AR was defined as recurrence detected on routine surveillance in the absence of symptoms. Baseline demographic and clinical characteristics were compared between study groups using chi-square and t-test. Kaplan-Meier and Cox survival analyses were performed to compare cancer-specific survival (CSS) and overall survival (OS) between AR and SR groups. Results: Of 3822 patients who underwent RC from 1980-2018 (with a median follow-up after RC of 2.4 years (IQR 1.1,5.5), a total of 1100 were subsequently diagnosed with recurrence, including 311 (28.3%) with AR and 789 (71.7%) with SR. Median time from RC to recurrence was longer in the AR group (13.2 months) than in the SR group (10.8 months; p = 0.01). Presenting symptoms included pain (70.2%), constitutional symptoms (50.7%), gastrointestinal symptoms (23.3%), and urinary symptoms (23.3%). Median follow-up after recurrence was 2.4 years (IQR 1.1-5.5), during which time 997 patients died, including 840 who died of bladder cancer. Compared to patients with SR, patients with AR had a longer median CSS (54.5 months vs 27.3 months, p < 0.001) and OS (43.0 months vs 25.8 months, p < 0.001). On multivariable Cox proportional hazards models adjusting for demographic and clinical factors, SR was associated with a significantly increased risk of cancer-specific (hazard ratio [HR] 1.66 [95% confidence interval 1.41-1.96], p < 0.0001) and all-cause mortality (HR 1.48 [1.23-1.71], p < 0.0001). Conclusions: SR after RC is associated with worse oncologic outcomes than post-RC recurrence detected by routine surveillance. As such, continued surveillance is warranted, while further study is needed to determine the optimal follow-up regimen balancing patient and disease risks.