Background: The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question.
Patients and methods: Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy.
Results: Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively.
Conclusion: Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy.
Implications for practice: High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is lacking. We show for the first time that systemic chemotherapy may be beneficial and result in one out of five poor prognosis patients becoming resectable or being spared from an extensive surgical approach. Although mores studies are needed to confirm these data, administering salvage systemic chemotherapy in this setting may have the potential to minimize morbidity associated with extensive surgical procedures and improve long-term oncological outcome.
摘要
背景. 尚未探索过局部晚期直肠癌（LARC）患者在新辅助放化疗失败后使用化疗挽救治疗的可能性。我们通过一项单中心回顾性分析来阐明这一问题。
患者和方法. 本研究纳入了在长期放化疗后不能手术或符合扩大手术[即, 超出全直肠系膜切除术（TME）范围]标准且接受挽救化疗的新诊断LARC患者。主要目的是估计化疗后适合行TME的患者比例。
结果. 共有45例合格患者（39例符合扩大手术标准, 6例无法手术切除）。43例患者之前同步接受放疗和化疗（中位剂量：54.0 Gy）。分别有40例（88.9%）和5例（11.1%）患者接受基于奥沙利铂和伊立替康的挽救化疗。8例（17.8%）患者在化疗后符合TME标准；10例（22.2%）患者的肿瘤边界清晰, 最终行TME；2例（4.4%）患者采取观察等待的方法进行管理。此外, 13例患者出于根治性目的行扩大手术。总人群的3年无进展生存率和5年总生存率分别为30.0%[95%置信区间（CI）：15.0‐46.0]和44.0%（95%CI：26.0‐61.0）。在行根治性切除术和”观察等待”的患者中, 3年无进展生存率和5年总生存率分别为52.0%（95%CI：27.0‐73.0]和67.0%（95%CI：40.0‐84.0）。
结论. 对于放化疗无效且不能手术或符合扩大手术（即, 超出TME范围）标准的LARC患者, 全身化疗可能是一种有效的挽救治疗策略。本研究表明, 20%的患者在全身化疗后可能进行手术切除或无需接受扩大手术。The Oncologist 2017;22:728–736
对临床实践的提示：对于标准放化疗后不能手术或符合扩大手术（即, 超出TME范围）标准的直肠癌患者而言, 尚无高质量的证据可供确定其最佳管理方法。本研究首次表明全身化疗具有潜在获益, 预后不良的患者在接受全身化疗后有20%可能进行手术切除或无需接受扩大手术。虽然需要开展更多研究来证实以上数据, 但在本研究条件下, 挽救性全身化疗有望将扩大手术的相关发病率降至最低并改善长期肿瘤学预后。
Keywords: Beyond total mesorectal excision surgery; Inoperable rectal cancer; Locally advanced rectal cancer; Neoadjuvant chemoradiotherapy; Salvage systemic chemotherapy.
© AlphaMed Press 2017.