Optimal Management of High-Risk T1G3 Bladder Cancer: A Decision Analysis

Abstract

BackgroundControversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3) bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE) and quality-adjusted life expectancy (QALE) for both of these treatments for men and women of different ages and comorbidity levels.Methods and FindingsWe evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1) Immediate cystectomy with neobladder creation versus (2) conservative management with intravesical bacillus Calmette-Guérin (BCG) and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients over the age of 70 y or those strongly averse to loss of sexual function, gastrointestinal dysfunction, or life without a bladder have a higher QALE with conservative therapy. The results of structural or probabilistic sensitivity analyses did not change the preferred treatment option. Model-predicted overall and disease-specific survival rates were similar to those reported in published studies, suggesting external validity.ConclusionsOur model is, to our knowledge, the first of its kind in bladder cancer, and demonstrated that younger patients with high-risk T1G3 bladder had a higher LE and QALE with immediate cystectomy. The decision to pursue immediate cystectomy versus conservative therapy should be based on discussions that consider patient age, comorbid status, and an individual's preference for particular postcystectomy health states. Patients over the age of 70 y or those who place high value on sexual function, gastrointestinal function, or bladder preservation may benefit from a more conservative initial therapeutic approach.

Cost‐effectiveness analysis of immediate radical cystectomy versus intravesical Bacillus Calmette‐Guerin therapy for high‐risk, high‐grade (T1G3) bladder cancer

“…Although our current model included the option of cystectomy after a T1G3 recurrence, which is a legitimate treatment approach in high-risk patients, sensitivity analyses in our previous work demonstrated that changes in model structure pertaining to the timing of cystectomy after T1G3 recurrence minimally influence health outcomes. 9 Fifth, we extrapolated utilities from nonbladder cancer health states because of the absence of utility data in this regard. Although we believe that this approach is reasonable, we acknowledge that it may introduce error into our model.…”

“…The details and structure of the original Markov model have been described elsewhere. 9 Briefly, patients in the hypothetical cohort who underwent immediate cystectomy were subject to a risk of postoperative mortality (Fig. 1).…”

“…The survival estimates of our model have been validated previously. 9 Briefly, for patients who underwent radical cystectomy, the 5-year overall and disease-specific survival rates generated by the model were 80% and 91%, respectively. The corresponding rates for patients who received intravesical BCG were 81% and 90%, respectively.…”

“…9 In the current analysis, we updated our model to meet 2 additional objectives. First, we analyzed the costs and cost-effectiveness of each strategy.…”

The management of BCG failure in non-muscle-invasive bladder cancer: an update

“…Recent data suggest that when cystectomy is performed following conservative attempts in cases of high-risk NMIBC, the 5-year postoperative survival rate is lower than reported in recent studies, especially when cystectomy is performed on a patient with disease that has progressed to T2, as opposed to patients with T1 NMIBC. 5 Kulkarni and colleagues recently evaluated 2 treatment strategies for high-risk T1G3 bladder cancer using a decisionanalytic Markov model 6 as follows: (1) Immediate cystectomy with neobladder creation versus (2) conservative management with intravesical BCG and delayed cystectomy in individuals with resistant or progressive disease. The authors demonstrated that younger patients with high-risk T1G3 bladder had a greater life expectancy and QOL following immediate cystectomy.…”