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

Date Published: September 25, 2007

Publisher: Public Library of Science

Author(s): Girish S Kulkarni, Antonio Finelli, Neil E Fleshner, Michael A. S Jewett, Steven R Lopushinsky, Shabbir M. H Alibhai, Michael J Droller

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.

Partial Text: In North America, more than 65,000 patients are diagnosed with bladder cancer annually [1]. The majority of cases are superficial transitional cell carcinoma (TCC), which are usually managed by transurethral resection (TURBT). High-grade superficial TCC that invades the lamina propria of the bladder is staged as T1G3 and may further be divided into high-risk (multifocal and/or associated carcinoma in situ [CIS]) or low-risk (solitary without associated CIS) categories [2].

We found that for an otherwise healthy, 60-y-old sexually potent man with high-risk T1G3 bladder cancer, the mean LE was 7.9 mo higher if he decided to undergo immediate radical cystectomy instead of conservative management. Consideration of QOL led to a slightly smaller gain of 4.2 mo in favor of early cystectomy but did not alter the preferred treatment option. Comorbidity was most influential on the treatment decision for patients between the ages of 60 and 70 y. One-way sensitivity analyses revealed that patients over the age of 70 or those strongly averse to loss of sexual function, gastrointestinal dysfunction, or life without a bladder had a higher QALE with conservative therapy. Neither structural sensitivity analyses nor probabilistic sensitivity analyses altered the optimal base case treatment strategy.



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