Abstract
Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy. To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer. A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma treated with SCRT-TNT or LCCRT. Markov modeling was used to model disease progression and patient survival after treatment in 3-month cycles. Data on probabilities and utilities were extracted from the literature. Costs were evaluated from the Medicare payer's perspective in 2020 US dollars. Sensitivity analyses were performed for key variables. Data were collected from October 3, 2020, to January 20, 2021, and analyzed from November 15, 2020, to April 25, 2021. Two treatment strategies, SCRT-TNT vs LCCRT with adjuvant chemotherapy, were compared. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefits. Effectiveness was defined as quality-adjusted life-years (QALYs). Both costs and QALYs were discounted at 3% annually. Willingness-to-pay threshold was set at $50 000/QALY. During the 5-year horizon, the total cost was $41 355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54 827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (-$141 256.77). The net monetary benefit was $69 300 for SCRT-TNT and $51 060 for LCCRT. Sensitivity analyses using willingness to pay at $100 000/QALY and $150 000/QALY demonstrated the same conclusion. These findings suggest that SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy. These data offer further rationale to support SCRT-TNT as a novel cost-saving treatment paradigm in the management of locally advanced rectal cancer.
Highlights
Sensitivity analyses using willingness to pay at $100 000/quality-adjusted life-year (QALY) and $150 000/QALY demonstrated the same conclusion. These findings suggest that shortcourse radiotherapy (SCRT)-total neoadjuvant therapy (TNT) followed by total mesorectal excision (TME) incurs lower cost and improved QALYs compared with conventional long-course chemoradiotherapy (LCCRT) followed by TME and adjuvant chemotherapy
Base Case Analysis For the SCRT-TNT group, the modeled 3-year locoregional recurrence (LRR) rate was 8% compared with 8% in the RAPIDO trial; cumulative distant metastasis rate, 21% compared with 20%; and overall survival rate, 88% compared with 89%10,16
The total cost was $41 355 and the QALYs were 2.21 for SCRT-TNT, and the total cost was $54 827 and the QALYs were 2.12 for LCCRT during the 5-year horizon. This resulted in an incremental cost-effectiveness ratio (ICER) of −$141 256.77 per QALY (Table 3), that is, SCRT-TNT was a cost-saving and dominating treatment strategy compared with LCCRT
Summary
Colorectal cancer is the second leading cause of cancer-related mortality in the US, with the country’s second-highest annual cost of $14.1 billion in 2010.1 Costs were projected to reach $17.4 billion in 2020.1 Standard of care in the management of locally advanced rectal cancer usually entails neoadjuvant long-course chemoradiotherapy (LCCRT) for 5 to 6 weeks,[2,3] followed by total mesorectal excision (TME).[4,5] this treatment strategy has led to decreased local recurrence rates of 4% to 9%,5-7 distant metastases remain the predominant site of recurrence,[8] and the management of metastatic rectal cancer incurs significant cost and morbidity.[9]To improve tumor downstaging before surgery, decrease the rates of distant metastases, and improve chemotherapy adherence, investigators more recently adopted a total neoadjuvant therapy (TNT) approach before TME.[10,11,12] Adding multiagent chemotherapy to the interval between radiotherapy and surgery has been shown to improve tumor downstaging[13] and chemotherapy tolerance.[14,15] Notably, in the phase 3 international multicenter trial Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO), preoperative short-course radiotherapy followed by TNT (SCRT-TNT) led to an increased pathological compete response rate, decreased disease-related treatment failure, and decreased distant metastatic disease at 3 years compared with preoperative LCCRT with or without adjuvant chemotherapy.[10,16] SCRT-TNT has shown oncologic promise and is recommended by the National Comprehensive Cancer Network,[17] the economic impact of this new therapy is not fully understood. To improve tumor downstaging before surgery, decrease the rates of distant metastases, and improve chemotherapy adherence, investigators more recently adopted a total neoadjuvant therapy (TNT) approach before TME.[10,11,12] Adding multiagent chemotherapy to the interval between radiotherapy and surgery has been shown to improve tumor downstaging[13] and chemotherapy tolerance.[14,15] Notably, in the phase 3 international multicenter trial Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO), preoperative short-course radiotherapy followed by TNT (SCRT-TNT) led to an increased pathological compete response rate, decreased disease-related treatment failure, and decreased distant metastatic disease at 3 years compared with preoperative LCCRT with or without adjuvant chemotherapy.[10,16]. Data were collected from October 3, 2020, to January 20, 2021
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