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Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States.

ABSTRACT: Randomized trials outside the U.S. have found non-inferior survival for neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced ovarian cancer (AOC). However, these trials reported lower overall survival and lower rates of optimal debulking than U.S. studies, leading to questions about generalizability to U.S. practice, where aggressive debulking is more common. Consequently, comparative effectiveness in the U.S. remains controversial. We reviewed U.S. comparative effectiveness studies of NACT versus PDS for AOC. Here we describe methodological challenges, compare results to trials outside the U.S., and make suggestions for future research. We identified U.S. studies published in 2010 or later that evaluated the comparative effectiveness of NACT versus PDS on survival in AOC through a PubMed search. Two independent reviewers abstracted data from eligible articles. Nine of 230 articles were eligible for review. Methodological challenges included unmeasured confounders, heterogeneous treatment effects, treatment variations over time, and inconsistent measurement of treatment and survival. Whereas some limitations were unavoidable, several limitations noted across studies were avoidable, including conditioning on mediating factors and immortal time introduced by measuring survival beginning from diagnosis. Without trials in the U.S., non-randomized studies are an important source of evidence for the ideal treatment for AOC. However, several methodological challenges exist when assessing the comparative effectiveness of NACT versus PDS in a non-randomized setting. Future observational studies must ensure that treatment is consistent throughout the study period and that treatment groups are comparable. Rapidly-evolving oncology data networks may allow for identification of treatment intent and other important confounders.

SUBMITTER: Cole AL

PROVIDER: S-EPMC6054914 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States.

Cole Ashley L AL Austin Anna E AE Hickson Ryan P RP Dixon Matthew S MS Barber Emma L EL

Cancer epidemiology 20180525

Randomized trials outside the U.S. have found non-inferior survival for neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced ovarian cancer (AOC). However, these trials reported lower overall survival and lower rates of optimal debulking than U.S. studies, leading to questions about generalizability to U.S. practice, where aggressive debulking is more common. Consequently, comparative effectiveness in the U.S. remains controversial. We reviewed U.S. comparative eff ...[more]

PMID: 29758492

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Project description:OBJECTIVES:Neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced epithelial ovarian cancer (AEOC) remains controversial in the United States. Generalizability of existing trial results has been criticized because of less aggressive debulking procedures than commonly used in the United States. As a result, economic evaluations using input data from these trials may not accurately reflect costs and outcomes associated with more aggressive primary surgery. Using data from an ongoing trial performing aggressive debulking, we investigated the cost-effectiveness and cost-utility of NACT versus PDS for AEOC. METHODS:A decision tree model was constructed to estimate differences in short-term outcomes and costs for a hypothetical cohort of 15,000 AEOC patients (US annual incidence of AEOC) treated with NACT versus PDS over a 1-year time horizon from a Medicare payer perspective. Outcomes included costs per cancer-related death averted, life-years and quality-adjusted life-years (QALYs) gained. Base-case probabilities, costs, and utilities were based on the Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasms trial. Base-case analyses assumed equivalent survival; threshold analysis estimated the maximum survival difference that would result in NACT being cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds. Probabilistic sensitivity analysis was used to characterize model uncertainty. RESULTS:Compared with PDS, NACT was associated with $142 million in cost savings, 1098 fewer cancer-related deaths, and 1355 life-years and 1715 QALYs gained, making it the dominant treatment strategy for all outcomes. In sensitivity analysis, NACT remained dominant in 99.3% of simulations. Neoadjuvant chemotherapy remained cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds if survival differences were less than 2.7 and 1.4 months, respectively. CONCLUSIONS:In the short term, NACT is cost-saving with improved outcomes. However, if PDS provides a longer-term survival advantage, it may be cost-effective. Research is needed on the role of patient preferences in tradeoffs between survival and quality of life.

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Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States.

Publications

Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States.

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