Summary High-quality evidence indicated that both neoadjuvant carboplatin/paclitaxel (CROSS) and cisplatin/5-fluorouracil (PF) regimens in combination with radiotherapy improve survival outcomes compared to surgery alone in patients with esophageal cancer. It is not yet known whether they may differ in terms of treatment burden and healthcare costs. A total of 232 Taiwanese patients with esophageal squamous cell carcinoma who had undergone neoadjuvant chemoradiotherapy (nCRT) with either the CROSS (n = 153) or the PF (n = 79) regimens were included. Hospital encounters and adverse events were assessed for determining treatment burden. Cost-effectiveness analysis was undertaken using the total costs incurred over 3 years in relation to overall survival (OS) and progression-free survival (PFS). Compared with PF, the CROSS regimen was associated with a lower treatment burden: shorter inpatient days on average (4.65 ± 10.05 vs. 15.14 ± 17.63 days; P < 0.001) and fewer admission requirements (70% of the patients were never admitted vs. 20% in the PF group; P < 0.001). Patients in the CROSS group experienced significantly less nausea, vomiting, and diarrhea. While the benefits observed in the CROSS group were associated with additional nCRT-related expenditures (1388 United States dollars [USD] of added cost per patient), this regimen remained cost-effective. At a willingness-to-pay threshold of 50,000 USD per life-year, the probability of the CROSS regimen to be more cost-effective than PF was 94.1% for PFS but decreased to 68.9% for OS. The use of the CROSS regimen for nCRT in patients with ESCC was associated with a lower treatment burden and was more cost-effective than PF.
Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the recommended treatment for patients with locally advanced esophageal cancer. However, not all patients who started nCRT will undergo esophagectomy and refusal is one of the main reasons. Although an active-surveillance strategy in patients with a clinically complete response after nCRT is increasingly implemented in clinical practice, the evidence is still immature and refusing surgery still comes with uncertain risk and outcomes. We aimed to study survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) who underwent nCRT followed by surgery versus patients who refused surgery after nCRT. Two hundred thirty patients treated between 2012–2020 at Chang-Gung Memorial Hospital were assessed. To balance confounders that could interfere with patients’ decision, baseline characteristics, year of treatment, type of nCRT regimen, adverse events during nCRT, timing of response evaluation, and result of response evaluation (Figure 1) were subjected to propensity score matching (PSM). Thirty-three patients refused surgery and were matched with 66 (of 146) patients who underwent surgery. Before PSM, the two groups had similar baseline characteristics. No significant differences were found in the choice of nCRT regimen nor the severity of adverse events during nCRT, except for the days between the end of nCRT and response evaluation, which was longer in the refusal group (31.7 ± 14.1 versus 37.4 ± 16.4, P = 0.047). Surprisingly, response evaluation results were also similar before PSM. Two patients refused surgery while having positive biopsies and 82% still had suspected nodal involvement on computerized or positron emission tomography scan. After PSM, 3-year overall survival was 59% versus 55% in the surgery and refusal group, respectively (P = 0.78). Our findings suggest that patients who refused surgery have similar survival outcomes as patients receiving esophagectomy after nCRT. However, after refusal, 85% still received additional chemoradiotherapy, 52% had disease progression within 16 months and 12% received salvage surgery eventually. Refusing surgery based on patients’ values and belief does not necessarily lead to worse survival outcomes, but future clinical trials should focus on standardization of additional therapy and follow-up after refusal to avoid uncertain outcomes.
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