LB803 - The Cost Effectiveness of Total Neoadjuvant Therapy with Selective Nonoperative Management: An Analysis Based on the OPRA Trial

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Purpose/Background: The clinical effectiveness of total neoadjuvant therapy (TNT) with selective nonoperative management (NOM) for locally advanced rectal cancer (LARC) was demonstrated in the OPRA trial. We examined the cost and quality-of-life implications of adopting this treatment approach.

Methods/Interventions: The OPRA trial randomized LARC patients to TNT in the form of induction systemic chemotherapy followed by chemoradiotherapy (INCT) or chemoradiotherapy followed by consolidation systemic chemotherapy (CNCT). TNT was followed by selective NOM in both treatment arms. Disease-free survival (DFS) was compared to historical DFS data for the standard of care (SOC): neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. Most patients had low tumors ( < 5 cm from the anal verge). W e compared clinical, cost, and quality-adjusted life year (QALY) outcomes between INCT, CNCT, and SOC using a Markov model with INCT and CNCT data from OPRA and SOC data from two prospective cohorts and published studies. The willingness-to-pay threshold was set to $50,000, and a probabilistic sensitivity analysis with 10,000 iterations was performed. Sensitivity analyses evaluated the cost-effectiveness of different surgical contexts and SOC variants. A 10-year time horizon analysis modelled additional long-term costs associated with surveillance, recurrence, low anterior resection syndrome, and stoma management.

Results/Outcomes: SOC was dominated in the base case analysis by both TNT approaches with selective NOM. CNCT was the least costly at MP$79,423 (Medicare proportionate dollars), followed by INCT at MP$81,098 and SOC at MP$88,413. INCT was associated with the highest number of QALYs at 3.14, followed by CNCT at 3.07 and SOC at 2.99. When willingness to pay exceeded MP$80,000 , >90% of iterations favored TNT with selective NOM. SOC was dominated in all sensitivity analyses except when omitting adjuvant chemotherapy without an impact on DFS. INCT was the preferred strategy for patients who would need a permanent colostomy, and CNCT was the preferred strategy if a restorative proctectomy would be feasible. In the long-term analysis, INCT was the preferred strategy, driven by higher QALYs. CNCT was more cost-effective than SOC when the proportion of patients entering NOM after TNT was ≥15%. For CNCT to be the preferred strategy relative to SOC without adjuvant therapy, the proportion of patients entering NOM needed to be ≥41%.

Conclusion/Discussion: TNT with selective NOM for LARC is more cost-effective than SOC. QALYs are highest with INCT, whereas the NOM rate is higher for CNCT. NOM with CNCT is especially cost-effective when surgery entails a low colorectal or coloanal anastomosis, but the cost-effectiveness of CNCT relative to SOC is dependent on CNCT being made available to a sufficiently large proportion of LARC patients. Additional analyses are needed to validate these findings from a societal perspective and in the context of other emerging treatment paradigms for LARC.