Cost-Effectiveness Analysis of Pembrolizumab for Bacillus Calmette-Guérin-Unresponsive Carcinoma In Situ of the Bladder.

PURPOSE: Patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ are treated with radical cystectomy or salvage intravesical chemotherapy. Recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive carcinoma in situ. MATERIALS AND METHODS: We used a decision-analytic Markov model to compare pembrolizumab, salvage intravesical chemotherapy (with gemcitabine-docetaxel induction+monthly maintenance) and radical cystectomy for patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ who are radical cystectomy candidates (index patient 1) or are unwilling/unable to undergo radical cystectomy (index patient 2). The model used a U.S. Medicare perspective with a 5-year time horizon. One-way and probabilistic sensitivity analyses were performed. Incremental cost-effectiveness ratios were compared using a willingness to pay threshold of $100,000/quality-adjusted life year. RESULTS: For index patient 1, pembrolizumab was not cost-effective relative to radical cystectomy (incremental cost-effectiveness ratios $1,403,008/quality-adjusted life year) or salvage intravesical chemotherapy (incremental cost-effectiveness ratios $2,011,923/quality-adjusted life year). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to radical cystectomy with a >93% price reduction. Relative to radical cystectomy, salvage intravesical chemotherapy was cost-effective for time horizons <5 years and nearly cost-effective at 5 years (incremental cost-effectiveness ratios $118,324/quality-adjusted life year). One-way sensitivity analysis revealed that salvage intravesical chemotherapy became cost-effective relative to radical cystectomy if 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 (incremental cost-effectiveness ratios $1,073,240/quality-adjusted life year). Pembrolizumab was cost-effective in 0% of 100,000 microsimulations in probabilistic sensitivity analyses for both index patients. CONCLUSIONS: At its current price, pembrolizumab is not cost-effective for bacillus Calmette-Guérin-unresponsive carcinoma in situ relative to radical cystectomy or salvage intravesical chemotherapy. Although gemcitabine-docetaxel is not cost-effective relative to radical cystectomy at 5 years, further studies may validate its cost-effectiveness if recurrence and metastasis thresholds are met.

Management of precancerous anal intraepithelial lesions in human immunodeficiency virus-positive men who have sex with men: Clinical effectiveness and cost-effectiveness.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management. METHODS: A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results-Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective. RESULTS: Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER] < $100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy. CONCLUSIONS: The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017;123:4709-4719. © 2017 American Cancer Society.

Surgical versus Medical Treatment of Ocular Surface Squamous Neoplasia: A Cost Comparison.

PURPOSE: The objective of this study was to compare the cost associated with surgical versus interferon-alpha 2b (IFNα2b) treatment for ocular surface squamous neoplasia (OSSN). DESIGN: A matched, case-control study. PARTICIPANTS: A total of 98 patients with OSSN, 49 of whom were treated surgically and 49 of whom were treated medically. METHODS: Patients with OSSN treated with IFNα2b were matched to patients treated with surgery on the basis of age and date of treatment initiation. Financial cost to the patient was calculated using 2 different methods (hospital billing and Medicare allowable charges) and compared between the 2 groups. These fees included physician fees (clinic, pathology, anesthesia, and surgery), facility fees (clinic, pathology, and operating room), and medication costs. Time invested by patients was calculated in terms of number of visits to the hospital and compared between the 2 groups. Parking costs, transportation, caregiver wages, and lost wages were not considered in our analysis. MAIN OUTCOME MEASURES: Number of clinic visits and cost of therapy as represented by both hospital charges and Medicare allowable charges. RESULTS: When considering cost in terms of time, the medical group had an average of 2 more visits over 1 year compared with the surgical group. Cost as represented by hospital charges was higher in the surgical group (mean, $17 598; standard deviation [SD], $7624) when compared with the IFNα2b group (mean, $4986; SD, $2040). However, cost between the 2 groups was comparable when calculated on the basis of Medicare allowable charges (surgical group: mean, $3528; SD, $1610; medical group: mean, $2831; SD, $1082; P = 1.00). The highest cost in the surgical group was the excisional biopsy (hospital billing $17 598; Medicare allowable $3528), and the highest cost in the medical group was interferon ($1172 for drops, average 8.0 bottles; $370 for injections, average 5.4 injections). CONCLUSIONS: Our data in this group of patients previously demonstrated equal efficacy of surgical versus medical treatment. In this article, we consider costs of therapy and found that medical treatment involved two more office visits, whereas surgical treatment could be more or equally costly depending on insurance coverage.

Cost-effectiveness of surveillance strategies after treatment for high-grade anal dysplasia in high-risk patients.

BACKGROUND: Anal cancer is one of the most common cancers affecting human immunodeficiency virus (HIV)-infected male patients. Currently, there is no consensus on posttreatment surveillance of HIV-infected men who have sex with men (MSM) who have been treated for high-grade intraepithelial neoplasia (HGAIN), the likely precursor to anal cancer. OBJECTIVE: The aim of this study was to assess the cost-effectiveness of a range of strategies for anal cancer surveillance in HIV-infected MSM previously treated for HGAIN. METHODS: We developed a Markov model to project quality-adjusted life expectancy, lifetime costs, and the incremental cost-effectiveness ratios of 5 strategies using high-resolution anoscopy (HRA) and/or anal cytology testing after treatment. RESULTS: Performing HRA alone at 6- and 12-month visits was associated with a cost-effectiveness ratio of $4446 per quality-adjusted life year gained. In comparison, combined HRA and anal cytology at both visits provided greater health benefit at a cost of $17,373 per quality-adjusted life year gained. Our results were robust over a number of scenarios and assumptions including patients' level of immunosuppression. Results were most sensitive to test characteristics and cost, as well as progression rates of normal to HGAIN and HGAIN to cancer. CONCLUSIONS: Our results suggest that combined HRA and anal cytology at 6 and 12 months may be a cost-effective surveillance strategy after treatment of HGAIN in HIV-infected MSM.

Emerging targeted therapies for bladder cancer: a disease waiting for a drug.

Urothelial cell carcinoma is the fifth most common cancer and the costliest to treat. This is largely because of all new cases, about 70% present as superficial disease and this while rarely fatal, tends to recur, requiring long-term follow-up and repeat interventions. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. Muscle-invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors such as lung, breast and prostate, been few in number and largely unsuccessful, with no new agents being registered in the last 20 years. Hence, bladder cancer represents a considerable opportunity and challenge for molecularly targeted therapy.

The Burden of Cervical Cancer in Korea: A Population-Based Study.

This study used the Korean National Health Insurance (NHI) claims database from 2011 to 2017 to estimate the incidence and the incidence-based cost of cervical cancer and carcinoma in situ of cervix uteri (CIS) in Korea. The primary outcome was the direct medical cost per patient not diagnosed with cervical cancer (C53) or CIS (D06) 2 years prior to the index date in the first year after diagnosis. A regression analysis was conducted to adjust for relevant covariates. The incidence of cervical cancer tended to decrease from 2013 to 2016, while that of CIS increased. In particular, the incidence rate of CIS in women in their 20 s and 30 s increased by 56.8% and 28.4%, respectively, from 2013 to 2016. The incidence-based cost of cervical cancer and CIS was USD 13,058 and USD 2695 in 2016, respectively, which increased from 2013. Multivariate regression analysis suggested that age was the most influential variable of the cost in both patient groups, and the cost was highest in those aged over 60, i.e., the medical cost was significantly lower in younger women than their older counterparts. These findings suggest that targeting younger women in cervical cancer prevention is a reasonable option from both economic and public health perspectives.

Hospitalization burden associated with malignant neoplasia and in situ carcinoma in vulva and vagina during a 5-year period (2009-2013) in Spain: An epidemiological study.

BACKGROUND: Vulvar and vaginal cancers are considered rare cancers in women. Human Papillomavirus is responsible for 30-76% of them. The aim of this study was to describe the burden of hospital admissions by malignant neoplasia (MN) and in situ carcinoma (ISC) of vulva and vagina from 2009 to 2013, in Spain METHODS: This observational, descriptive study used discharge information obtained from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos, CMBD, provided by the Ministry of Health. RESULTS: From 2009-2013, we found 9,896 hospitalizations coded as MN or ISC of vulva and vagina. Mean age of hospitalization was 69.94 ±â€¯15.16 years; average length of hospital stay (ALOS) was 10.02 ±â€¯12.40 days, and mean hospitalization costs were 5,140.31 ±â€¯3,220.61 euros. Mean hospitalization rate was 9.874 per 100,000 women aged >14 years old (95% CI: 9.689-10.058); mean mortality rate was 0.932 per 100,000 women aged >14 years old (95% CI: 0.872-0.991) and mean case fatality rate was 9.438% (95% CI: 8.862-10.014). CONCLUSION: MN and ISC of vulva and vagina are responsible for a considerable hospitalization burden. Information about these hospitalizations could be useful for cost effectiveness analysis and monitoring of HPV vaccination effectiveness.

Cost Effectiveness of the Oncotype DX DCIS Score for Guiding Treatment of Patients With Ductal Carcinoma In Situ.

Purpose The Oncotype DX DCIS Score short form (DCIS Score) estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery without adjuvant radiation therapy (RT). We determined the cost effectiveness of strategies using this test. Materials and Methods We developed a Markov model simulating 10-year outcomes for 60-year-old women eligible for the Eastern Cooperative Oncology Group E5194 study (cohort 1: low/intermediate-grade DCIS, ≤ 2.5 cm; cohort 2: high-grade DCIS, ≤ 1 cm) with each of five strategies: (1) no testing, no RT; (2) no testing, RT only for cohort 2; (3) no RT for low-grade DCIS, test for intermediate- and high-grade DCIS, RT for intermediate- or high-risk scores; (4) test all, RT for intermediate- or high-risk scores; and (5) no testing, RT for all. We used utilities and costs extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women needed to irradiate per IBE prevented. Results No strategy using the DCIS Score was cost effective. The most cost-effective strategy (RT for none or RT for all) was sensitive to small differences between the utilities of receiving or not receiving RT and remaining without recurrence. The numbers needed to irradiate per IBE prevented were 10.5, 9.1, 7.5, and 13.1 for strategies 2 to 5, respectively, relative to strategy 1. Conclusion Strategies using the DCIS Score lowered the proportion of women undergoing RT per IBE prevented. However, no strategy incorporating the DCIS Score was cost effective. The cost effectiveness of RT was exquisitely utility sensitive, highlighting the importance of engaging patient preferences in this decision. Physicians should discuss trade-offs associated with omitting or adding adjuvant RT with each patient to maximize quality-of-life outcomes.

Cost-effectiveness of radiation therapy following conservative surgery for ductal carcinoma in situ of the breast.

PURPOSE: To assess the cost-effectiveness of radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) after breast-conserving surgery (BCS). METHODS AND MATERIALS: A Markov model was constructed for a theoretical cohort of 55-year-old women with DCIS over a life-time horizon. Probability estimates for local noninvasive (N-INV), local invasive (INV), and distant recurrences were obtained from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17. Utilities for eight nonmetastatic health states were collected from both healthy women and DCIS patients. Direct medical (2002 Medicare fee schedule) and nonmedical costs (time and transportation) of RT were ascertained. RESULTS: For BCS + RT vs. BCS alone, the estimated N-INV and INV rates at 12 years were 9% and 8% vs. 16% and 18%, respectively. The incremental cost of adding RT was 3300 US dollars despite an initial RT cost of 8700 US dollars due to higher local recurrence-related salvage costs incurred with the BCS alone strategy. An increase of 0.09 quality-adjusted life-years (QALYs) primarily reflected the lower risk of INV with RT, resulting in an incremental cost-effectiveness ratio (ICER) of 36,700 US dollars/QALY. Sensitivity analyses revealed the ICER to be affected by baseline probability of a local recurrence, relative efficacy of RT in preventing INV, negative impact of an INV on quality of life, and cost of initial RT. Cost of salvage BCS + RT and source of utilities (healthy women vs. DCIS patients) influenced the ICER albeit to a lesser degree. CONCLUSIONS: Addition of RT following BCS for patients with DCIS should not be withheld because of concerns regarding its cost-effectiveness.

See-and-treat in the management of high-grade squamous intraepithelial lesions of the cervix: a resource utilization analysis.

OBJECTIVE: To use activity-based costing techniques to compare see-and-treat with conventional evaluation and treatment of women presenting with a screening Papanicolaou smear demonstrating high-grade squamous intraepithelial lesion (SIL). METHODS: A total of 4000 theoretical patients were assumed to be evaluated and treated following one of four management algorithms: conventional algorithm I, with colposcopy and directed biopsies, followed by cryotherapy or cold-knife conization; conventional algorithm II, substituting the loop electrosurgical excision procedure for cold-knife conization; conventional algorithm III, substituting the loop electrosurgical excision procedure for cold-knife conization and cryotherapy; or see-and-treat algorithm IV, using the loop electrosurgical excision procedure. Costs associated with patient management in each algorithm were calculated including those for the procedure, patient time, physician time, and disposable expenses, as well as costs to manage complications, treatment failures, and follow-up for 1 year. RESULTS: Algorithm I was the most expensive, costing $899,405 for 1000 patients with high-grade SIL. Substituting the loop electrosurgical excision procedure for cold-knife conization (algorithm II) decreased the cost by 32%, whereas substituting it for cryotherapy also (algorithm III) reduced the cost by only 25%. The most cost-effective management was the see-and-treat single visit of algorithm IV. This strategy cost $531,281, offering a 41% cost reduction compared with algorithm I. CONCLUSION: A see-and-treat approach to the management of women with high-grade SIL, although incorporating more procedures, offers significant cost savings over conventional management algorithms.

Decreased incidence of cervical cancer in medicare-eligible California women.

OBJECTIVE: To determine if the incidence of invasive cervical cancer relative to carcinoma in situ decreased in Medicare-eligible women. METHODS: A retrospective cohort was amassed from the California Cancer Registry database. The hypothesis was prospectively specified. Mean ratio of invasive (International Federation of Gynecology and Obstetrics Stages I-IV) to in situ cervical carcinoma in 1988-1990 versus 1991-1995 was stratified by age (24 or younger, 25-44, 45-64, 65 or older) and race (all races, whites, blacks, Hispanics, Asian/Pacific Islanders). RESULTS: The mean ratio of invasive to in situ cervical cancer incidence for women at least 65 years old was lower in 1991-1995 compared with 1988-1990 (P <.001, 95% confidence interval 0.893, 0.954); and had decreased more than observed for women aged 45-64 and 25-44, for all races combined, and for white women. The decreased ratio of invasive to in situ cancer for blacks, Hispanics, and Asian/Pacific Islanders at least 65 years old was no different than the decreased ratio in younger women. CONCLUSION: In California, in the 5 years after the 1990 change in Medicare funding statutes for cervical cytology screening, the ratio of invasive cervical cancer to in situ disease decreased more in Medicare-eligible patients than in younger women.

Management of superficial bladder cancer in a community setting.

Over the past four or five years, the urologist in private practice has gained experience using mitomycin in the treatment of superficial bladder cancers. Indications for use of mitomycin include carcinoma in situ (CIS), more than two or three recurrences on successive cytoscopic examinations of superficial transitional cell carcinomas, the presence of multiple transitional cell carcinomas at the time of initial examination when it was believed that all tumor could not be removed cystoscopically, and prophylaxis. The regimen for mitomycin has changed over time; currently the standard regimen is 40 mg mitomycin in 40 cc sterile water given intravesically once a week for eight weeks followed by routine cystoscopic examinations every three months and maintenance therapy, if indicated, of 40 mg mitomycin once a month. Results following use of this regimen in private practice have been most encouraging. Complications have been minimal. Only 1 patient had to discontinue therapy because of side effects, and 1 patient underwent radical cystectomy for recurrent disease after partial cystectomy and mitomycin therapy. Patients still receiving treatment include 1 patient who had not responded after initial treatment and who is being followed up for possible recurrence. Mitomycin therapy appears to be effective in controlling superficial bladder cancer and, possibly, carcinoma in situ, with minimal side effects and good patient compliance.

Management of patients with Bacilli Calmette-Guérin-refractory carcinoma in situ of the urinary bladder: cost implications of a clinical trial for valrubicin.

OBJECTIVE: This study was undertaken to identify the expected first- and second-year clinical costs associated with intravesical valrubicin therapy, using a decision analytic model, for patients with Bacilli Calmette-Guérin (BCG)-refractory carcinoma in situ (CIS) of the urinary bladder. BACKGROUND: Cancer of the urinary bladder is the fourth most common malignancy in men and the sixth most common noncutaneous carcinoma overall. One histopathologic stage of bladder cancer is CIS, for which BCG intravesical immunotherapy is the first-line therapy. Radical cystectomy has been recommended for patients with CIS who do not respond to or become refractory to therapy with BCG. Surgery, however, may not be appropriate for all patients, especially those who are ineligible for the lengthy procedure because of advanced age or comorbidities and those who prefer alternative nonsurgical management. For these groups, intravesical valrubicin therapy is a plausible alternative. METHODS: Models were developed and populated with data from 1 open-label study of 90 patients, information from the medical literature, and input from clinical experts. The analysis was conducted from the payor perspective for direct costs only. RESULTS: Our data indicate that first- and second-year expected costs for valrubicin therapy are $19,912 and $23,496, respectively. Expected cost for radical cystectomy was also evaluated, since some patients may have no other option if drug therapy fails. CONCLUSION: Our cost-consequence analysis and clinical data provide decision-makers with tools to aid in global budgetary projections of fractional and total expected health care costs associated with the management BCG-refractory CIS of the urinary bladder.

Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: a screening strategy in the perspective of rural India.

The predominance of cervical cancer in India can mostly be attributed to the lack of early screening. The objective of the present study has been, therefore, to determine a cost-effective oncogenic human papillomavirus (HPV)-based cervical cancer screening plan for rural Indian women. The results showed that in normal women, highest prevalence of HPV 16/18 infection was in the age group < or =23 years and lowest in > or =44 years with an insignificant change in between. HPV 16/18 infection was significantly associated with cervical erosion at age < or =23 years, but not with cytology or visual inspection with acetic acid testing at any age. The low-grade cytological lesions, however, increased only with increase in age. Fourteen per cent of the cervical malignancy was also found to be present in the age group 24-33 years with an 87% HPV infection. Here we proposed a cost-effective screening scheme in which HPV testing must be performed in women (a) < or =23 years with cervical erosion and (b) 24-43 years, as an adjunct to Pap smears (both HPV and cytology were prevalent in this group). For women > or =44 years, HPV testing might not be useful, since abnormal cytology was more prominent over the viral infection. We infer that by not performing HPV test in the group < or =23 years, approximately 76% of the high-risk HPV-infected individuals potentially "at risk" for developing cervical cancer might be missed.

Quality of life, functional outcome, and costs of early glottic cancer.

OBJECTIVE: To analyze quality of life, functional outcome, and hidden costs by primary treatment with surgery or radiation therapy in patients with early glottic cancer. STUDY DESIGN: Retrospective study in a tertiary care facility. METHODS: A group of 101 patients with carcinoma in situ and T1 invasive squamous cell carcinoma treated primarily with either surgery or radiation, between January 1990 and December 2000, were identified from searching our tumor registry. Patients completed two previously validated questionnaires and one local questionnaire. Statistical significance was assessed with the rank sum test, chi2 test, or Fisher's Exact test. RESULTS: Questionnaires were completed in 59% (44 of 74) of the surgical cohort and 41% (11 of 27) of the radiation therapy cohort. The primary surgical treatments were endoscopic excision (86%), hemilaryngectomy (12%), and total laryngectomy (1%). Patient-reported problems with swallowing, chewing, speech, taste, saliva, pain, activity, recreation, and appearance showed no difference between the endoscopic excision or radiation therapy cohorts. Comparing endoscopic excision versus radiation therapy, respectively, median number of treatments (2 vs. 35), total median travel distance (150 vs. 660 miles), total median travel time (180 vs. 1440 min), and total median number of hours of work missed (76 vs. 24) all differed significantly (P <.01). CONCLUSIONS: Almost all patients with early glottic cancer, whether treated with surgery or radiation therapy, reported excellent quality of life outcomes and functional results. In addition to actual costs, the hidden costs for radiation therapy versus endoscopic excision were all greater in terms of total number of hours of work missed, total travel time, and total travel distance.

Compliance and efficiency before and after implementation of a clinical practice guideline for laryngeal carcinomas.

We evaluated whether the implementation of a nationwide clinical practice guideline for diagnosis, treatment and follow-up of laryngeal carcinomas led to changes in hospital costs, balanced against clinical changes observed following the guideline's implementation. Charts of 822 patients with larynx carcinoma (459 treated before the introduction of the guideline and 363 thereafter) in five hospitals were retrospectively investigated. In all phases, no differences in total hospital costs were observed after the guideline's implementation. Total mean costs were Euro 3,207 (95%CI 3,091-3,395) for diagnosis, Euro 3,169 (2,153-4,182), Euro 5,026 (3,996-6,057), Euro 6,458 (5,579-7,337), Euro 8,037 (7,469-8,606), Euro 12,765 (10,763-14,769), Euro 19,227 (16,848-21,605) for treatment of dysplasia, carcinoma in situ, T1, T2, T3 and T4 carcinoma, respectively, and Euro 1,856 (1,491-2,220) for 1 year disease-free follow-up. In an earlier study, we observed several positive changes after the guideline's implementation. Balanced against the equal costs before and after the guideline's implementation, we conclude that the efficiency of the care process improved.