Determining optimal first-line chemotherapy for good and intermediate prognosis testicular germ cell tumors using decision analysis.

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209 Background: Since 80-90% of testicular germ cell tumors (GCTs) are cured after first line therapy alone, minimizing toxicity should be an important consideration in the initial treatment decision between cisplatin and carboplatin. Cisplatin has been shown to be superior in 5-year disease-free survival, but cisplatin use confers a higher risk of key long-term toxicities. This study aims to quantify this trade-off between disease-free survival and toxicities using decision analysis. Methods: We developed a mathematical decision-analytic model that simulates competing strategies of initial treatment with cisplatin or carboplatin in terms of treatment response, long-term toxicity, and mortality associated with first, second, and third line therapies for patients with good and intermediate prognosis testicular GCTs and a median age of 20 years at diagnosis. Treatment toxicities included ototoxicity, neurotoxicity, and nephrotoxicity. Monthly probabilities were weighted means derived from a systematic review of total follow-up data reported in seminal clinical trials. The model projected life expectancies for each strategy. Sensitivity analysis was conducted to examine the impact of uncertain inputs and assumptions. Results: The life expectancies at diagnosis for cisplatin and carboplatin strategies were 436.1 months (36.3 years) and 663.2 months (55.3 years) respectively. Sensitivity analyses revealed life expectancy figures largely dependent on the risk of nephrotoxicity occurrence from first line therapy and death from nephrotoxicity. Unless these base monthly probabilities were reduced by 87% and 99% respectively, carboplatin consistently yielded higher life expectancy than cisplatin. Conclusions: Under the current model, first line carboplatin therapy yields longer life expectancy than cisplatin, but this difference is highly sensitive to variables concerning nephrotoxicity. These preliminary results suggest that first line carboplatin therapy could yield higher life expectancy, though this result may be mediated by inclusion of other factors in future analyses, including updated estimates of mortality from nephrotoxicity or other toxicities.