The Financial Burden of Guideline-recommended Cancer Medications for Metastatic Urothelial Carcinoma.

Bladder cancer is a significant global health concern owing to its prevalence, negative impact on quality of life, and high treatment costs. Treatment for metastatic urothelial carcinoma (mUC) traditionally relies on platinum-based chemotherapy regimens. However, clinical trial results have led to the approval of immune checkpoint inhibitors (ICIs) as viable treatment options. We assessed the escalating costs and economic viability of mUC treatment guidelines in Europe. We used a pragmatic approach that involved: (1) collection of the costs of the recommended medications in the five most populous European countries; (2) conversion of the costs into international dollars to account for differences in purchasing power parity among countries; (3) evaluation of the cost trends over time; and (4) comparison of the medication costs to World Health Organization thresholds. Introduction of ICIs in European guidelines substantially increased the cost of medications for mUC. Intriguingly, important differences across European countries emerged: the annual cost of medications was twofold higher in Italy than in France and the UK. Despite limitations, our study sheds light on the escalating costs and economic challenges of mUC treatment, and highlights the need for assessments of sustainable and cost-effective management approaches. PATIENT SUMMARY: We looked at the costs of treatments for metastatic bladder cancer and found that costs have been rising over time, especially with the introduction of new immune therapies, with notable differences among European countries. While these new treatments improve patient outcomes, they also come with a high price tag, which could strain health care budgets. Our results suggest that cost-effectiveness studies will be essential in determining the best and most sustainable treatment strategies in the future.

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study.

BACKGROUND: Open radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. OBJECTIVE: To assess the cost-effectiveness of RARC compared to ORC in bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. RESULTS AND LIMITATIONS: The mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791-€18 720) for ORC and €21 266 (95% CI €19 163-€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431-€22 642) for ORC and €24 896 (95% CI €21 925-€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74-0.85) compared to 0.81 QALYs (95% CI 0.77-0.85) for ORC patients, resulting in a mean QALY difference of -0.02 (95% CI -0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. CONCLUSIONS: RARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. PATIENT SUMMARY: This study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive. This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214).

Evidence-based Assessment of Current and Emerging Bladder-sparing Therapies for Non-muscle-invasive Bladder Cancer After Bacillus Calmette-Guerin Therapy: A Systematic Review and Meta-analysis.

CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of ≥50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

A cost-effectiveness modeling study of robot-assisted (RARC) versus open radical cystectomy (ORC) for bladder cancer to inform future research.

BACKGROUND: Open radical cystectomy (ORC) is regarded the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. However, it is unclear whether RARC provides value for money. OBJECTIVE: To identify the main evidence gaps and main drivers of cost-effectiveness, comparing RARC to ORC. DESIGN, SETTING, AND PARTICIPANTS: A decision analytical model was developed to study the 30d and 90d postoperative complications with RARC versus ORC and their related cost in bladder cancer patients. Input data were derived from systematic literature searches, meta-analyses, internal databases and expert opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cost per saved complication (in Clavien-Dindo grading) was determined. Deterministic sensitivity analyses was performed to search for threshold values for RARC to become cost saving. Uncertainty was addressed using probabilistic sensitivity analyses. RESULTS: The expected 30d and 90d risk for a minor complication was lower for RARC than ORC (37% vs. 45% and 32% vs. 36%). The expected 30d and 90d risk of RARC versus ORC for a major complication was 18% vs. 23% and 16% vs. 25%. The 30d and 90d extra costs needed to prevent one major complication were €62,582 and €37,007, respectively. Data on the impact of complications on quality of life were lacking. Three scenarios resulted in cost savings for RARC: operating time (threshold: ≤175min), length of stay (≤4d), and RARC equipment (≤€281). CONCLUSION: Current evidence suggests that it is unlikely that RARC will become less expensive than ORC. However, RARC might result in fewer complications. To determine value for money, research is needed into the consequences of these complications in terms of quality of life. PATIENT SUMMARY: Economic modeling showed that RARC might result in fewer complications, but is more expensive than ORC. Future research should focus on the impact on quality of life.

Assessment of the efficacy of repeated instillations of mitomycin C mixed with a thermosensitive hydrogel in an orthotopic rat bladder cancer model.

BACKGROUND: We investigated a thermoreversible hydrogel that is highly viscous at body temperature, while fluid-like at a low temperature, thus aiming for a slow and prolonged intravesical drug release. Our study purposed to assess antitumor efficacy of mitomycin C (MMC) mixed with hydrogel in an orthotopic rat bladder cancer model. METHODS: Bladders of female Fischer F344 rats were grafted with 1.5 × 106 AY-27 urothelial carcinoma cells. On day 5, tumor presence was assessed by cystoscopy and rats were divided into six groups (five treatment, one control, n = 10/group). Intravesical treatments (0.5 mg or 1 mg MMC-H2O or MMC-hydrogel, or 2 mg MMC-hydrogel) were administered on days 5, 8 and 11. Rats were sacrificed at day 14 and bladders were evaluated. RESULTS: Rats with tumor at cystoscopy (47/60) were evaluated for efficacy. At necropsy, all control animals (8/8) had tumors. No microscopic tumors were present in the 0.5 mg and 1 mg MMC-hydrogel groups compared with 2/8 and 1/8 rats in the 0.5 mg and 1 mg MMC-H2O groups (p = 0.47 and p = 1.00, respectively).Greater toxicity was seen in animals treated with MMC-hydrogel compared with MMC-H2O, as demonstrated by lower body weights at necropsy (p = 0.000) and a tendency for more severe clinical signs in the 1 and 2 mg MMC-hydrogel groups. Rats that died prematurely received 1 mg (4/10) or 2 mg (9/10) of MMC-hydrogel. CONCLUSIONS: Under the current model conditions it is unclear whether instillation of MMC-hydrogel is more effective than MMC-H2O. Nonetheless, the observed difference in toxicity, acting as a surrogate marker for systemic MMC exposure in the MMC-hydrogel-treated rats, supports the prolonged drug release mechanism of the hydrogel.

Economic Burden of Bladder Cancer Across the European Union.

BACKGROUND: More than 120,000 people are diagnosed annually with bladder cancer in the 28 countries of the European Union (EU). With >40,000 people dying of it each year, it is the sixth leading cause of cancer. However, to date, no systematic cost-of-illness study has assessed the economic impact of bladder cancer in the EU. OBJECTIVE: To estimate the annual economic costs of bladder cancer in the EU for 2012. DESIGN, SETTING, AND PARTICIPANTS: Country-specific cancer cost data were estimated using aggregate data on morbidity, mortality, and health care resource use, obtained from numerous international and national sources. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health care costs were estimated from expenditures on primary, outpatient, emergency, and inpatient care, as well as medications. Costs of unpaid care and lost earnings due to morbidity and early death were estimated. RESULTS AND LIMITATIONS: Bladder cancer cost the EU €4.9 billion in 2012, with health care accounting for €2.9 billion (59%) and representing 5% of total health care cancer costs. Bladder cancer accounted for 3% of all cancer costs in the EU (€143 billion) in 2012 and represented an annual health care cost of €57 per 10 EU citizens, with costs varying >10 times between the country with the lowest cost, Bulgaria (€8 for every 10 citizens), and highest cost, Luxembourg (€93). Productivity losses and informal care represented 23% and 18% of bladder cancer costs, respectively. The quality and availability of comparable cancer-related data across the EU need further improvement. CONCLUSIONS: Our results add to essential public health and policy intelligence for delivering affordable bladder cancer care systems and prioritising the allocation of public research funds. PATIENT SUMMARY: We looked at the economic costs of bladder cancer across the European Union (EU). We found bladder cancer to cost €4.9 billion in 2012, with health care accounting for €2.9 billion. Our study provides data that can be used to inform affordable cancer care in the EU.

Clinical and cost effectiveness of hexaminolevulinate-guided blue-light cystoscopy: evidence review and updated expert recommendations.

CONTEXT: Non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates. OBJECTIVE: To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input. EVIDENCE ACQUISITION: PubMed and conference searches, supplemented by personal experience. EVIDENCE SYNTHESIS: Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time. CONCLUSIONS: HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system. PATIENT SUMMARY: Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours.

Cost-effectiveness of magnetic resonance (MR) imaging and MR-guided targeted biopsy versus systematic transrectal ultrasound-guided biopsy in diagnosing prostate cancer: a modelling study from a health care perspective.

BACKGROUND: The current diagnostic strategy using transrectal ultrasound-guided biopsy (TRUSGB) raises concerns regarding overdiagnosis and overtreatment of prostate cancer (PCa). Interest in integrating multiparametric magnetic resonance imaging (MRI) and magnetic resonance-guided biopsy (MRGB) into the diagnostic pathway to reduce overdiagnosis and improve grading is gaining ground, but it remains uncertain whether this image-based strategy is cost-effective. OBJECTIVE: To determine the cost-effectiveness of multiparametric MRI and MRGB compared with TRUSGB. DESIGN, SETTING, AND PARTICIPANTS: A combined decision tree and Markov model for men with elevated prostate-specific antigen (>4 ng/ml) was developed. Input data were derived from systematic literature searches, meta-analyses, and expert opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Quality-adjusted life years (QALYs) and health care costs of both strategies were modelled over 10 yr after initial suspicion of PCa. Probabilistic and threshold analyses were performed to assess uncertainty. RESULTS AND LIMITATIONS: Despite uncertainty around the presented cost-effectiveness estimates, our results suggest that the MRI strategy is cost-effective compared with the standard of care. Expected costs per patient were € 2423 for the MRI strategy and € 2392 for the TRUSGB strategy. Corresponding QALYs were higher for the MRI strategy (7.00 versus 6.90), resulting in an incremental cost-effectiveness ratio of € 323 per QALY. Threshold analysis revealed that MRI is cost-effective when sensitivity of MRGB is ≥ 20%. The probability that the MRI strategy is cost-effective is around 80% at willingness to pay thresholds higher than € 2000 per QALY. CONCLUSIONS: Total costs of the MRI strategy are almost equal with the standard of care, while reduction of overdiagnosis and overtreatment with the MRI strategy leads to an improvement in quality of life. PATIENT SUMMARY: We compared costs and quality of life (QoL) of the standard "blind" diagnostic technique with an image-based technique for men with suspicion of prostate cancer. Our results suggest that costs were comparable, with higher QoL for the image-based technique.

Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature.

CONTEXT: Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL. CONCLUSIONS: Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.

Program for laparoscopic urological skills assessment: setting certification standards for residents.

AIM: There is growing pressure from the government and the public to define proficiency standards for surgical skills. Aim of this study was to estimate the reliability of the Program for Laparoscopic Urological Skills (PLUS) assessment and to set a certification standard for second-year urological residents. METHODS: Fifty participants were assessed on performance time and performance quality to investigate the reliability of the PLUS assessment. Generalisability coefficient of 0.8, on a scale of 0 to 1.0, was considered to indicate good reliability for assessment purposes. Pass/fail standards were based on laparoscopic experience: Novices, intermediates, and experts (>100 procedures). The pass/fail standards were investigated for the PLUS performances of 33 second-year urological residents. RESULTS: Fifteen novices, twenty-three intermediates and twelve experts were included. An inter-trial reliability of >0.80 was reached with two trials for each task. Inter-rater reliability of the quality measurements was 0.79 for two judges. Pass/fail scores were determined for the novice/intermediate boundary and the intermediate/expert boundary. Pass rates for second-year residents were 63.64% and 9.09%, respectively. CONCLUSION: The PLUS assessment is reliable for setting a certification standard for second-year urological residents that serves as a starting point for residents to proceed to the next level of laparoscopic competency.

Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy.

CONTEXT: This review focuses on the prediction of recurrence and progression in non-muscle invasive bladder cancer (NMIBC) and the treatments advocated for this disease. OBJECTIVE: To review the current status of epidemiology, recurrence, and progression of NMIBC and the state-of-the art treatment for this disease. EVIDENCE ACQUISITION: A literature search in English was performed using PubMed and the guidelines of the European Association of Urology and the American Urological Association. Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Special attention was given to fluorescent cystoscopy, the new World Health Organisation 2004 classification system for grade, and the role of substaging of T1 NMIBC. EVIDENCE SYNTHESIS: In NMIBC, approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of cancer in western society and the most expensive cancer per patient. Recurrence (in < or = 80% of patients) is the main problem for pTa NMIBC patients, whereas progression (in < or = 45% of patients) is the main threat in pT1 and CIS NMIBC. In a recent European Organisation for Research and Treatment of Cancer analysis, multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Tumour grade, stage, and CIS are the most important variables for progression. Treatment ranges from transurethral resection (TUR) followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes, re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients to early cystectomy for treatment-refractory high-risk NMIBC. CONCLUSIONS: NMIBC is a heterogeneous disease with varying therapies, follow-up strategies, and oncologic outcomes for an individual patient.

Perioperative instillation therapy in superficial bladder cancer: is it effective regarding outcome and costs?

PURPOSE OF REVIEW: This article reviews the current knowledge concerning immediate intravesical instillation therapy in nonmuscle-invasive bladder cancer after transurethral resection of the bladder tumour, with emphasis on the literature of the last few years. RECENT FINDINGS: A review was conducted on the recent literature available by PubMed database on the subject of immediate bladder chemotherapy after transurethral resection of the bladder tumour and its recent developments. SUMMARY: A single immediate bladder instillation with chemotherapy will give 39% reduction of recurrence. Numbers needed to treat to prevent one recurrence are estimated at 8.5. In intermediate and high-risk bladder cancer, the immediate postoperative instillation does not give sufficient reduction in recurrence rate to leave out subsequent bladder instillations. The significant reduction of recurrences, the mild side-effects of the treatment and the clear cost-effectiveness make one immediate instillation a valuable addition to transurethral resection of the bladder tumour in the treatment of nonmuscle-invasive bladder cancer. Points of controversy are the true numbers needed to treat to prevent a recurrence and the type of recurrences that will be prevented. No new types of instillation are added recently to the ones available, but promising types are under investigation of which pharmacokinetic studies have shown acceptable rates of side-effects.

High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies.

OBJECTIVES: Histopathology of prostate needle biopsies (PNBs) is an important part in the diagnosis, prognosis and treatment evaluation of prostate cancer. The determination of metabolite levels in the same biopsies may have additional clinical value. Here, we demonstrate the use of non-destructive high resolution magic angle spinning (HRMAS) proton NMR Spectroscopy for the assessment of metabolic profiles of prostate tissue in PNBs as commonly obtained in standard clinical practice. MATERIALS AND METHODS: PNBs that were taken routinely from 48 patients suspected of having prostate cancer were subjected to HRMAS proton NMR spectroscopy. Subsequent histopathology of the same biopsies classified the tissue either as cancer (n = 10) or benign (n = 30). RESULTS: Some practical aspects of this assessment were evaluated, such as typical spectral contamination caused by the PNB procedure. Significant metabolic differences were found between malignant and benign tissue using a small set of ratio's involving signals of choline compounds, citrate and lactate. Moreover, significant correlations were observed between choline, total choline, and citrate over creatine signal ratios and the Gleason scores of tumor in PNBs and of tumor in the whole prostate. CONCLUSION: This preliminary study indicates that HRMAS NMR of routinely obtained PNBs can provide detailed metabolic information of intact prostate tissue with clinical relevance.

The role of hexaminolevulinate fluorescence cystoscopy in bladder cancer.

Non-muscle-invasive bladder cancer is labor intensive and costly to manage. Owing to long-term survival rates and life-long monitoring and treatment, it is the most expensive cancer to manage in per-patient terms. Significant costs are attributable to the treatment of recurrences and complications. Fluorescence-guided cystoscopy, using 5-aminolevulinic acid (ALA) or its hexyl ester, hexaminolevulinate 5-ALA (Hexvix [HAL], Photocure, Oslo, Norway), improves the detection of bladder tumors, particularly carcinoma in situ, compared with standard white-light cystoscopy. The quality of transurethral resection of the bladder tumor is also improved. It has been shown that improved tumor detection leads to better patient management and, in the case of ALA, reduced long-term recurrence rates and costs. Long-term studies in this area with HAL are ongoing. The technique is well tolerated and is a useful adjunct to white-light cystoscopy.

The efficacy of different follow-up strategies in clinical stage I Non-seminomatous Germ Cell Cancer: a Markov simulation study.

OBJECTIVE: There is no universally accepted standard protocol for surveillance of patients with clinical stage I Non Seminomatous Germ Cell Tumors (CS I NSGCT). Prospective studies to compare different follow-up policies have not been performed, even though a great deal of time and resources is spent in surveillance. In this study, we constructed a Markov model to evaluate the impact of different follow-up strategies on disease-specific mortality (DSM) and life expectancy (LE) of patients with CS I NSGCT. METHODS: A discrete time non-homogeneous semi-Markov model was used to simulate different follow-up strategies for a hypothetical population of CS I NSGCT patients. Estimates of the model parameters were based on the literature. Output parameters were DSM and LE. Three different strategies were compared: (1) the intensive The Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NCI/AvL) protocol; (2) the European Association of Urology (EAU) protocol; and (3) a hypothetical minimal protocol (i.e. follow-up limited to the first two years). Furthermore, we evaluated the impact of abdominal CT scans and chest X-rays on DSM. RESULTS: Comparing with the EAU protocol (DSM: 3.05%; LE: 53.3 years), the intensive NCI/AvL protocol leads to a 1.2% lower DSM and a 6 months higher LE (DSM: 1.81%; LE: 53.9 years). The hypothetical follow-up scenario during the first two years shows a DSM of 6.83% and an LE of 51.4 years. Abdominal CT scans of the retroperitoneal lymph nodes appear to be important, while chest X-rays have little impact on DSM. CONCLUSION: A follow-up policy limited to the first two years will result in an unacceptable high percentage of death from disease (6.83%). The relatively small benefit of an intensive follow-up protocol as proposed by the NCI/AvL, compared to that of the EAU, must be weighed against its economic and psychological costs. Our model suggests that CT-scanning is essential for a low DSM, whereas the large number of X-rays seem to have little additional effect.