Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark; Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark.
Lancet Oncol. 2015 Aug;16(8):919-27. doi: 10.1016/S1470-2045(15)00120-5. Epub 2015 Jul 5.
Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer.
Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m(2)) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints.
Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23·9 months (IQR 15·3-31·0). Local recurrence in the observation group at 1 year was 15·5% (95% CI 3·3-26·3). The most common acute grade 3 adverse event during treatment was diarrhoea, which affected four (8%) of 51 patients. Sphincter function in the observation group was excellent, with 18 (72%) of 25 patients at 1 year and 11 (69%) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 (IQR 0-0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths.
High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer.
CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research.
腹会阴联合切除术是治疗远端 T2 或 T3 直肠癌患者的标准治疗方法；然而，该手术范围广泛且具有破坏性，目前正在探索替代的治疗策略。我们进行了一项前瞻性观察性试验，以评估高剂量放疗联合化疗后观察（等待观察）是否对低位直肠癌的非手术治疗成功。
将原发性、可切除的 T2 或 T3、N0-N1 低位直肠腺癌患者给予放化疗（肿瘤部位 60 Gy/30 次，选择性淋巴结体积 50 Gy/30 次，腔内近距离放射治疗 5 Gy 推量，口服替加氟-尿嘧啶 300 mg/m²），每周 5 天，持续 6 周。在基线、治疗期间（第 2、4 和 6 周）以及治疗结束后 6 周对肿瘤进行内镜检查和活检。对于完全临床肿瘤消退、肿瘤部位活检阴性、CT 和 MRI 检查无淋巴结或远处转移的患者，在治疗结束后 6 周被分配到观察组（等待观察）。所有其他患者均转诊至标准手术。观察组患者密切随访内镜检查和选择性部位活检，如果局部复发则进行手术切除。主要终点是观察组患者分配后 1 年内的局部肿瘤复发。该研究在 ClinicalTrials.gov 注册，编号为 NCT00952926。目前招募已结束，但仍在继续随访次要终点。
2009 年 10 月 20 日至 2013 年 12 月 23 日，我们共纳入 55 例患者。这些患者来自丹麦三个外科单位，并在丹麦一家三级癌症中心（Vejle 医院，Vejle）接受治疗。在符合条件的 51 例患者中，40 例有临床完全缓解并被分配至观察组。观察组患者局部复发的中位随访时间为 23.9 个月（IQR：15.3-31.0）。观察组患者 1 年时的局部复发率为 15.5%（95%CI：3.3-26.3）。治疗期间最常见的急性 3 级不良事件是腹泻，影响了 51 例患者中的 4 例（8%）。观察组患者的肛门功能极佳，25 例患者中有 18 例（72%）在 1 年时、16 例患者中有 11 例（69%）在 2 年时报告完全没有粪便失禁，且 Jorge-Wexner 评分中位数在所有时间点均为 0（IQR：0-0）。最常见的晚期毒性是直肠黏膜出血；30 例患者中有 2 例（7%）在 1 年时、17 例患者中有 1 例（6%）在 2 年时报告出现 3 级出血。没有发生意外的严重不良反应或与治疗相关的死亡。
对于低位直肠癌患者，高剂量放化疗联合观察可能是腹会阴联合切除术的一种安全替代方法。
CIRRO-丹麦 Lundbeck 基金会放疗介入研究中心和丹麦战略研究理事会。
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