Litwin, Mark S.

395 Background: Patients with BCG-unresponsive carcinoma in situ (CIS) are treated with radical cystectomy (RCx) or salvage intravesical chemotherapy (SIC). Recently, the FDA approved pembrolizumab for BCG-unresponsive CIS +/- papillary tumors. Given the costs and toxicities of pembrolizumab, it remains unclear whether its benefits are sufficient to warrant widespread use for BCG-unresponsive CIS. To that end, we conducted a cost-effectiveness analysis comparing pembrolizumab with RCx and SIC (using gemcitabine-docetaxel as the prototypical regimen) for patients with BCG-unresponsive CIS. Methods: A decision-analytic Markov model compared pembrolizumab, SIC (with gemcitabine-docetaxel), and RCx for patients with BCG-unresponsive CIS +/- papillary tumors who are RCx candidates (index patient 1) or are unwilling/unable to undergo RCx (index patient 2). Each treatment option was a Markov node containing distinct variations of the following health states: surveillance, recurrence, progression to MIBC, progression to metastasis, treatment toxicity, and death. Incremental Cost-Effectiveness Ratios (ICERs) were compared using a willingness-to-pay threshold of $100,000/Quality-adjusted life year (QALY). The model used a US Medicare perspective with a 5-year time horizon for the base case. One-way and probabilistic sensitivity analyses were performed for all model parameters. Results: For index patient 1, pembrolizumab was not cost-effective vs. RCx (ICER $1,403,008) or SIC (ICER $2,011,923). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to RCx with a > 93% price reduction. Relative to RCx, SIC was cost-effective for time horizons < 5 years and nearly cost-effective at 5 years (ICER $118,324). One-way sensitivity analysis revealed that SIC became cost-effective relative to RCx if its risk of recurrence or metastasis at 2 years was less than 55% or 5.9%, respectively. For index patient 2, pembrolizumab required > 90% price reduction to be cost-effective vs. RCx (ICER $1,073,240). Probabilistic sensitivity analyses revealed that pembrolizumab was unlikely to be cost-effective even at high willingness-to-pay thresholds. Further sensitivity analyses found that no two-way combination of extrapolated values resulted in pembrolizumab being favored over RCx or SIC for either index patient. Conclusions: Based on decision-analytic Markov modeling of treatment options for patients with BCG-unresponsive CIS, pembrolizumab was unlikely to be cost-effective without a > 90% price reduction. While both RCx and SIC were more cost-effective than pembrolizumab, further studies may validate the cost-effectiveness of gemcitabine-docetaxel relative to RCx if the recurrence and metastasis thresholds are met. Overall, our model supports the preferential use of RCx and SIC over pembrolizumab for BCG-unresponsive CIS.

ABSTRACT Introduction The optimal approach for identification and evaluation of the sexual problems in men and women in primary care or general medicine practice has not been consensed. Aim To provide recommendations/guidelines concerning state-of-the-art knowledge for clinical evaluation and management strategies in the evaluation and treatment of sexual dysfunction in men and women, emphasizing evidence-based medicine and a patient-centered framework. Methods An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Clinical Evaluation and Management Strategies Committee, there were 12 experts from five countries. Main Outcome Measure Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. Results Three concepts underlie sexual medicine management: (i) adoption of a patient-centered framework for evaluation and treatment; (ii) application of the principles of evidence-based medicine in diagnostic and treatment planning; and (iii) use of a unified management approach in men and women. When taken together, these three principles provide a balanced and integrated approach to sexual dysfunction management. Common algorithms for diagnosis and management of men and women with sexual dysfunction, brief sexual symptom checklists, basics in history and physical examination, indications for specialized referral and development of a follow-up strategy are presented. Conclusions More research is needed in understanding the role of evidence-based and patient-centered medicine in the clinical evaluation and management strategies of men and women with sexual dysfunction.