Department of General and Visceral Surgery, Endocrine Surgery, and Coloproctology, Municipal Hospital of Munich-Neuperlach, Munich, Germany.
Department of General and Abdominal Surgery, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.
J Clin Oncol. 2023 Aug 20;41(24):4025-4034. doi: 10.1200/JCO.22.02166. Epub 2023 Jun 19.
We investigated whether neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer can be restricted to those at high risk of locoregional recurrence (LR) without compromising oncological outcomes.
In a prospective multicenter interventional study, patients with rectal cancer (cT2-4, any cN, cM0) were classified according to the minimal distance between the tumor, suspicious lymph nodes or tumor deposits, and mesorectal fascia (mrMRF). Patients with a distance >1 mm underwent up-front total mesorectal excision (TME; low-risk group), whereas those with a distance ≤1 mm and/or cT4 and cT3 tumors in the lower rectal third received nCRT followed by TME surgery (high-risk group). The primary end point was 5-year LR rate.
Of the 1,099 patients included, 884 (80.4%) were treated according to the protocol. A total of 530 patients (60%) underwent up-front surgery, and 354 (40%) had nCRT followed by surgery. Kaplan-Meier analyses revealed 5-year LR rates of 4.1% (95% CI, 2.7 to 5.5) for patients treated per protocol, 2.9% (95% CI, 1.3 to 4.5) after up-front surgery, and 5.7% (95% CI, 3.2 to 8.2) after nCRT followed by surgery. The 5-year rate of distant metastases was 15.9% (95% CI, 12.6 to 19.2) and 30.5% (95% CI, 25.4 to 35.6), respectively. In a subgroup analysis of 570 patients with lower and middle rectal third cII and cIII tumors, 257 (45.1%) were at low-risk. The 5-year LR rate in this group was 3.8% (95% CI, 1.4 to 6.2) after up-front surgery. In 271 high-risk patients (involved mrMRF and/or cT4), the 5-year rate of LR was 5.9% (95% CI, 3.0 to 8.8) and of metastases 34.5% (95% CI, 28.6 to 40.4); disease-free survival and overall survival were the worst.
The findings support the avoidance of nCRT in low-risk patients and suggest that in high-risk patients, neoadjuvant therapy should be intensified to improve prognosis.
我们研究了新辅助放化疗（nCRT）是否可以仅限于局部区域复发（LR）风险高的直肠癌患者，而不影响肿瘤学结果。
在一项前瞻性多中心干预性研究中，根据肿瘤、可疑淋巴结或肿瘤沉积物与直肠系膜筋膜（mrMRF）之间的最小距离，对直肠癌患者（cT2-4，任何 cN，cM0）进行分类。距离>1mm 的患者接受直接全直肠系膜切除术（TME；低危组），而距离≤1mm 和/或下段直肠第三部分 cT4 和 cT3 肿瘤的患者接受 nCRT 后再行 TME 手术（高危组）。主要终点是 5 年 LR 率。
在 1099 例患者中，884 例（80.4%）按方案治疗。共有 530 例（60%）患者接受了直接手术，354 例（40%）患者接受了 nCRT 后手术。Kaplan-Meier 分析显示，按方案治疗的患者 5 年 LR 率为 4.1%（95%CI，2.7 至 5.5），直接手术治疗的患者为 2.9%（95%CI，1.3 至 4.5），nCRT 后手术治疗的患者为 5.7%（95%CI，3.2 至 8.2）。远处转移的 5 年发生率分别为 15.9%（95%CI，12.6%至 19.2%）和 30.5%（95%CI，25.4%至 35.6%）。在 570 例低位和中位直肠第三 cII 和 cIII 肿瘤患者的亚组分析中，257 例（45.1%）为低危。该组患者直接手术后 5 年 LR 率为 3.8%（95%CI，1.4%至 6.2%）。在 271 例高危患者（累及 mrMRF 和/或 cT4）中，LR 的 5 年率为 5.9%（95%CI，3.0%至 8.8%），转移的 5 年率为 34.5%（95%CI，28.6%至 40.4%）；无病生存率和总生存率最差。
研究结果支持在低危患者中避免 nCRT，并提示在高危患者中，应加强新辅助治疗以改善预后。
