ASCO GI 2025丨早期直肠癌新辅助放化疗缓解后是否有必要进行根治性手术？这两项研究或可揭晓答案
文摘
健康
2025-01-23 20:46
北京
随着内镜微创手术技术的发展与推广，早期直肠癌行局部切除的临床疗效已经得到广泛的认可。中低位局部进展期直肠癌由于具有较高的局部复发率及区域淋巴结转移率，遵循全直肠系膜切除（TME）原则进行根治性手术长期以来被认为是直肠癌治疗的"金标准"。然而，根治术对直肠及其周围器官造成的损伤使得患者术后肛门功能与生活质量显著下降。新辅助放化疗策略的开展，使得局部进展期直肠癌可以达到明显降期，肿瘤显著退缩，甚至达到临床完全缓解（cCR）的效果。对于这部分患者是否有必要进行根治性手术一直是结直肠外科学界热议的话题。在刚刚召开的2025年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI 2025）上发表的两项Ⅱ期研究分别对无淋巴结转移低位直肠癌患者接受新辅助化疗后，实施局部切除（LE）的可行性（摘要号：148）和早期远端直肠癌在接受全程新辅助放化疗（TNT）后行LE的有效性和安全性（摘要号：177）进行了探讨，为上述问题提供了佐证。《肿瘤瞭望消化时讯》特对该两项研究进行了整理，以飨读者无淋巴结转移低位直肠癌保器官治疗的Ⅱ期研究：临床结局与患者报告结局更新
TME是治疗直肠癌的一种非常有效的方法，但术后复发率和死亡率较高。当前局部晚期直肠癌的器官保留（OP）治疗已取得成功，但针对无淋巴结转移（NN）的低位直肠癌的研究尚不充分。本项由研究者发起的临床试验（IIT）旨在确定在无淋巴结转移低位直肠癌患者接受新辅助化疗后，成功实施LE的可行性。本研究是一项单臂Ⅱ期IIT，以获得机构审查委员会（IRB）批准，纳入临床分期为T1~3、N0的低位直肠腺癌患者（肿瘤距肛缘<6 cm）。患者接受6个周期的FOLFOX方案化疗（5-FU快速静脉注射400 mg/m2，持续静脉滴注2400 mg/m2，亚叶酸钙400 mg/m2，奥沙利铂85 mg/m2）。对化疗有应答的患者在6~12周后接受LE（经肛切除）。为防止隐匿性淋巴结转移并减少肠道内复发，LE后进行放化疗（CXRT，卡培他滨825 mg/m2和长期放疗至54 Gy）。主要终点为新辅助化疗后成功进行LE的患者比例（NCT03548961）。共纳入19例低位直肠癌患者，其中9例为女性，诊断时平均年龄为65岁。T分期如下：T1期1例（5%），T2期11例（58%），T3期7例（36%）。18例（95%）患者完成了至少5个周期的新辅助化疗，16例（84%）接受了LE。19例患者中有79%达到切缘阴性，达到研究主要终点（P< 0.001）；10例（53%）患者肿瘤分期降低，16例接受LE的患者中有5例（31%）达到完全病理缓解。4例（21%）（均为T2期）患者未达到主要终点（其中3例对化疗应答不足，1例LE后切缘阳性），其中3例经挽救治疗后生存（2例接受CXRT，1例接受TME），1例因感染死亡（非相关并发症）。所有16例接受LE的患者均完成了CXRT。中位随访时间25.5个月，15例成功实现器官保留的患者中，未报告局部复发，1例研究入组时肺结节未达到转移阈值的患者最终发展为明确的肺转移。中位无病生存期（DFS）未达到。患者报告结局（PRO）评估显示，新辅助化疗后患者身体健康评分略有下降，但在随访时已恢复到基线水平，心理健康评分未见下降。未来将展示症状特异性生活质量（性功能和肠道功能）和长期生存数据。在无淋巴结转移低位直肠癌患者中，新辅助化疗联合LE可实现器官保留，超过四分之三的患者获得切缘阴性的LE，实现长期局部控制和保留生活质量。目前有研究正在探索无淋巴结转移直肠癌的手术治疗方法（NCT03259035）。本项研究方法为该领域日益增多的证据提供了补充，并将提供在这种背景下通过辅助放化疗防止隐匿性淋巴结转移获益的早期证据。OP-TNT：早期远端直肠癌行全程新辅助放化疗后进行局部切除治疗的Ⅱ期研究
手术是错配修复功能正常（pMMR）早期远端直肠癌（RC）的标准治疗方法，但全程新辅助放化疗（TNT）后采用观察和等待策略可在一定程度上替代手术。然而，长期数据显示，三分之一的患者在两年内出现局部生长（主要位于直肠壁）。本研究旨在探讨早期远端直肠癌（临床分期为cT1~3N0M0）TNT后行LE的有效性和安全性，以期保留器官。该研究是一项单臂、Ⅱ期前瞻性试验，纳入年龄≥18岁，体能状态评分为0~1，新诊断的、经活检证实的pMMR/微卫星稳定（MSS）RC，肿瘤位于距肛缘≤5 cm处，临床分期为cT1~3N0M0的患者。给予患者TNT方案治疗：6个周期的CapOx方案（卡培他滨1000 mg/m2，口服，每日两次，第1~14天；奥沙利铂130 mg/m2，静脉注射，每日一次，第1天，每3周一次），联合同步长程放疗（LCRT）（盆腔照射45 Gy/25次，肿瘤床同步加量至50 Gy/25次）。LCRT完成后12周进行评估，达到cCR或近临床完全缓解（ncCR）的患者接受LE，而LE后病理分期>ypT1、切缘阳性或存在神经血管侵犯的患者则建议行TME。主要终点为3年器官保留率，次要终点包括病理完全缓解率（pCR）（包括LE和TME后的缓解情况）、不良反应率、3年无病生存率（DFS）和3年总生存率（OS）。从2022年10月至2024年8月，共有52例患者完成治疗。评估时患者中位年龄和中位随访期间分别为58.3岁和11个月。其中，78.8%的患者MRI分期为T3，76.9%的患者肿瘤位于距肛缘≤3 cm处。在52例可评估的患者中，82.7%达到cCR/ncCR并接受LE（6例经内镜切除，37例经经肛微创手术）。在这些患者中，25.6%在LE后发现残留肿瘤，其中6例接受根治性手术，5例拒绝手术。9例未达到cCR或ncCR的患者接受TME，其中6例确认为pCR。总pCR率为73.1%。所有患者中有3例接受腹会阴联合切除术，保肛率为94.2%。安全性方面，未报告3级或4级不良事件，且无治疗相关死亡。局部切除后的主要不良事件为持续1~3个月的前切除综合征。中期分析结果显示，TNT后达到cCR/ncCR的患者中存在肿瘤残留，与先前报道的复发率相似，因此LE策略或可成为保留器官的有效措施，目前研究正继续长期随访，以获得更有利的证据。Phase II study of organ preservation (OP) in node-negative (NN) low rectal cancer (RC): Updated clinical and patient reported outcomes (PROs).Background:Total mesorectal excision (TME) is a highly effective treatment for rectal cancer (RC) but is associated with significant morbidity and mortality. Organ preservation (OP) approaches for locally advanced RC have been successful but not well studied for node-negative (NN) low RC. The objective of this investigator-initiated trial (IIT) is to determine the feasibility of performing successful local excision (LE) after neoadjuvant chemotherapy (CTX) in NN low RC.Methods:With IRB approval, patients (pts) with clinical stage T1-3, N0 low rectal adenocarcinomas (<6 cm from anal verge) were included in this single arm phase II IIT. Pts received 6 cycles of FOLFOX (5-FU bolus 400 mg/m2 and infusion 2400?mg/m2, Leucovorin 400 mg/m2, Oxaliplatin 85 mg/m2). Those with evidence of a response underwent LE (transanal excision) 6-12 weeks later. To target occult nodal metastases and reduce in-bowel recurrences, LE was followed by chemoradiotherapy ([CXRT] capecitabine 825 mg/m2 and long course RT to 54 Gy). The primary endpoint was the proportion of pts with successful LE after neoadjuvant CTX (NCT03548961).Results:Nineteen pts with low RC were enrolled; nine were female, and the mean age at diagnosis was 65 years. T stage was as follows: T1- 1(5%), T2 - 11(58%), T3 - 7(36%). Eighteen (95%) pts completed at least 5 cycles of neoadjuvant Ctx and 16/19 (84%) underwent LE. Negative margins were achieved in 79% (15/19), meeting our primary endpoint (p < 0.001). Ten (53%) were downstaged, and complete pathological response was achieved in 5/16 (31%) of pts who underwent LE. Four (21%) pts (all T2 stage) did not meet the primary endpoint (3 with inadequate response to CTX and 1 with LE and positive margins). Of these, three were salvaged (2 with CXRT; 1 with TME), and one died of infection (unrelated complication). All 16 who underwent LE completed CXRT. Of the 15 pts with successful OP at a median follow-up of 25.5 months, no local recurrences have been reported and 1 pt with lung nodules below the threshold for metastases at study entry ultimately developed clear lung metastases. Median DFS was not reached.?Patient reported outcomes (PRO) assessment revealed a slight decline in physical health scores after neoadjuvant CTX but improved to baseline at follow-up. No decline was seen in mental health scores. Symptom specific QOL (sexual and bowel function) and long-term survival data will be presented.Conclusions:Neoadjuvant CTX and LE allows for OP in NN low RC and results in a margin negative LE in over three fourths of pts with durable long term local control and preserved QOL. Ongoing trials are investigating an OP approach in NN RC (NCT03259035). Our approach adds to the mounting evidence and will provide early data of the benefit of adjuvant chemoradiation to target occult nodes in this setting.OP-TNT: Phase II study of total neoadjuvant chemoradiotherapy followed by local resection for early distal rectal carcinoma.Surgery is standard of care for pMMR early distal rectal cancer (RC), which can be partially exempted by totally neoadjuvant chemoradiotherapy (TNT) followed by watch and wait. But long-term data showed that 1/3 patients had local growth( mostly in the rectal wall)in two years. This study investigates the efficacy and safety of TNT followed by local excision( LE) for early distal rectal carcinoma (cT1-3N0M0) in order to preserve organs.In this single-arm, phase 2 prospective trial, patients were eligible if they were aged 18 years or older, with a performance status of 0-1,newly diagnosed, biopsy proven pMMR/MSS RC which located ≤5cm from the anal verge and staged as cT1-3N0M0. Patients were assigned to receive TNT: 6 courses of CapOx(capecitabine 1000 g/m2 PO BID D1-14, oxaliplatin 130 mg/m2 IV QD D1,Q3W), combined with concurrent long-course radiotherapy (LCRT)(45 Gy/25 Fx to the pelvis with an SIB of 50 Gy/25 Fx to the tumor bed). Evaluation was performed 12 weeks after completion of LCRT. Patients who achieved a clinical complete response (cCR) or near clinical complete response (ncCR)were assigned to LE, whereas those with >ypT1, positive margin, or neurovascular invasion after LE were recommended for total mesorectal excision (TME). The primary endpoint is the 3-year organ-preserving rate. Secondary endpoints include the pathological complete response (pCR)(encompassing response after LE and TME), adverse effects rate, 3y-disease-free survival (DFS)and 3y-overall survival (OS)rate.From October 2022 to August 2024, 52 patients had completed therapy. Median age at evaluation and follow-up duration were 58.3 years and 11 months. Of the patients 78.8% (41/52) were defined as MRI stage T3, and 76.9%(40/52) located ≤3cm from the anal verge. Of 52 evaluable patients ,82.7% (43/52) achieved cCR/ncCR and had LE (6 via endoscopic resection and 37 through trans-anal minimally invasive surgery). Among these patients, 25.6% (11/43) were found to have residual tumors after LE, of which 6 were radical-operated while 5 refused this intervention. Nine patients who did not achieve cCR or ncCR received TME resection, and 6 of them were confirmed as pCR. The total pCR rate was 73.1% (38/52). Of all patients, 3 underwent abdominoperineal resection, and sphincter-preserving rate was 94.2%(49/52). No grade 3 or 4 adverse events were reported, and there were no treatment-related deaths. The main adverse event after local resection was the 1-3 months anterior resection syndrome.The results of interim analysis showed that tumor residue was found in patients with cCR/ncCR after TNT, similar to the regrowth rate previously reported. LE strategy may become prevention. Long-term outcomes are being followed up.声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。
“肿瘤瞭望消化时讯”读者专属微信群建好了，快快加入吧。扫描“肿瘤瞭望消化时讯”小助手二维码（微信号：xhsx2021），回复“肿瘤瞭望消化时讯读者”，ta会尽快拉您入群滴！
（来源：肿瘤瞭望消化时讯）
凡署名原创的文章版权属“肿瘤瞭望消化时讯”所有。欢迎个人转发分享。其他任何媒体、网站如需转载或引用本网版权所有之内容须在醒目位置处注明转自“肿瘤瞭望消化时讯”
