Clatterbridge Cancer Centre, Liverpool, UK.
Department of Surgery and Cancer, Imperial College London, London, UK.
Colorectal Dis. 2023 Nov;25(11):2160-2169. doi: 10.1111/codi.16773. Epub 2023 Oct 13.
Nonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X-ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months.
OPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2-3a-b, cN0-1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m ) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively.
Between July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow-up of 38.2 months (range: 34.2-42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien-Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19-0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost.
Dose escalation can facilitate nonsurgical treatment for cT2-3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.
直肠癌的非手术治疗联合放化疗越来越受到关注，因为它避免了全直肠系膜切除术（TME）和造口术。OPERA 试验旨在评估与外部束放射治疗（EBRT）增敏相比，接触式 X 射线近距离放射治疗（CXB）增敏是否能提高器官保留率。有研究表明，剂量升级会对手术结果产生不利影响，因此我们报告了 OPERA 试验中 36 个月时 TME 的结果。
OPERA 是一项欧洲多中心 3 期临床试验（NCT02505750），将 cT2-3a-b、cN0-1、M0 的患者随机分为 EBCRT（45Gy 分 25 次，每周 5 次，同时口服卡培他滨 825mg/m2）后行 EBRT 增敏（9Gy 分 5 次，每天 1 次）与 EBCRT 后行 CXB 增敏（90Gy 分 3 次，每周 4 次）。患者在治疗开始后 14、20 和 24 周进行评估。对于在治疗后 24 周达到临床完全缓解（cCR）的患者，采用观察等待管理。根据患者和外科医生的偏好，对于残留疾病或局部复发，可选择局部切除（LE）或 TME 手术。前瞻性记录手术发病率和死亡率。
2015 年 7 月至 2020 年 6 月，共有 148 例患者入组，其中 141 例在 2022 年 3 月可评估。在中位随访 38.2 个月（范围：34.2-42.5）时，66 例（47%）患者接受了手术。共 27 例（20%）患者行局部切除术，39 例（29%）行 TME 手术，22/39（56%）行前切除术，17/39（44%）行腹会阴直肠切除术。R0 切除率为 87%。无死亡病例，6 例（15%）患者发生 Clavien-Dindo IIIb 级并发症。尽管 CXB 增敏后 TME 率有统计学意义下降（HR 0.38，95%CI：0.19-0.74，p=0.00419），但接受 EBRT 和 CXB 增敏的患者之间的手术结果无差异。
对于适合但希望避免 TME 手术和造口术的 cT2-3 直肠癌患者，剂量升级可促进非手术治疗。如果需要 TME 手术，则可以安全有效地进行。
