虽然它的症状出现早，但临床上误诊的不少見，主要因为它的症状，包括大便外裹血，便后鲜血，和痔疮十分相似。要是肿瘤围着腸壁生长而没有形成息肉，指检或腸镜或许不一定发现有异常。关键是若病人症状持续存在时，要想到直腸癌，对腸壁行活检，必要时可以在麻醉下，由外科医生扩张肛门，在直视下行活检。
一旦诊断成立，需要做以下的检查作临床分期： 1）结腸镜； 2）核磁共振以确立深度，和淋巴结是否有转移； 3）胸腹盆腔CT 或 PET 扫描； 4）CEA（血癌胚抗原）。
治疗方法根据临床以上检查的分类而定。
1）T1（肿瘤侵犯到粘膜下层）或T2（肌层），而无淋巴结转移：经腹切除。术后病理若仍为T1或T2，不必进一步治疗，随访即可。若术后病理为T3，T4或有淋巴结转移，需要化疗–>放化疗，或放化疗–>化疗，见下。
2）T3（肿瘤穿透粘膜肌层而侵犯到浆膜层），或T4（肿瘤侵犯到直腸周围的脏器），或有淋巴结转移，可以先放化疗–>手术–>化疗，或先化疗–>放化疗–>手术。
放化疗：放疗和同时服用希罗达（周一到周五），或放疗和静脉连续滴注5－氟尿嘧啶。
化疗：FOLFOX（奥沙利铂，5－氟尿嘧啶和亚叶酸钙，见结肠–>淋巴结转移一节）, 或CapeOx（以希罗达代替5－氟尿嘧啶）。以上两种方案都属首选。也可以用5－氟尿嘧啶或希罗达。化疗不超过6個月。
参考文献： N Engl J Med 2004; 350:2343-2351. N Engl J Med 2005; 352: 2696-2704. J Clin Onc 2002: 20: 1744-1750.局部晚期直肠癌的治疗：ASCO 指南 Management of locally advanced rectal cancer: ASCO guideline
请参阅 “最近进展 10/20/2024”
Please see Recent progress 10/24/2024
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FOLFOX 在局部晚期直肠癌新辅助治疗并不劣于放化疗 (7/23/2023)
FOLFOX was non-inferior to chemoradiation in rectal cancer
方法: 这是一项随机III期临床试验（PROSPECT），符合条件的患者(临床分期为 T2 淋巴结阳性、T3 淋巴结阴性或 T3 淋巴结阳性且适合保留括约肌手术的直肠癌患者),以非盲方式随机分配至 6 个周期的改良 FOLFOX6（试验组）或放化疗（对照组），在 5.5 周内给予 5,040 cGy，同时口服卡培他滨或静脉注射 5-FU 进行化疗。 试验组的参与者在化疗后重新分期。 如果肿瘤消退 ≥ 20%，则绕过放射治疗而接受直肠手术，并进行全直肠系膜切除。 反应欠佳（肿瘤消退 < 20%）的患者在手术前接再受了放化疗。 主要终点是无病生存期。 局部复发时间, 总生存期, 完全（R0）切除率, 完全缓解和毒性是次要终点。
结果:从 2012 年 6 月到 2018 年 12 月，1,194 名参与者被随机分配,1,128 名患者开始接受治疗（试验组 585 名，对照组 543 名）。 两组患者的特征非常平衡。 平均年龄为 57 岁。 两组的肿瘤位置相似（试验组距肛门边缘分别为 8.6 厘米相对于对照组 8.5 厘米）。 两组中 84.4% 的参与者均进行了盆腔 MRI 基线分期。 分配时患有临床淋巴结阳性肿瘤的参与者比例在试验组中为 60.3%，在对照组中为 63.5%。 由于 FOLFOX 的反应 < 20% 或不耐受，试验组中有 53 名参与者 (9.1%) 接受了化放疗。 经过 227 次事件和中位随访 58 个月后，试验组的 5 年无病生存率为 80.8%，而放化疗组（对照组）的 5 年无病生存率为 78.6%（HR 0.92，90.2% CI [0.74，1.14]；分层非劣效性 P = 0.0051），满足非劣效性标准。5 年总生存率分别为 89.5% 相对于 90.2% (HR 1.04, 0.74, 1.44) 。 另外, 完全切除率分别为98.9% 相对于97.1%; 病理性完全响应率分别为21.9% 相对于24.3%;手术径向切缘阳性率分别为1.2% 相对于1.5%。
试验组术前 ≥ 3 级不良事件发生的频率更高（41.0%相对于 22.8%），而对照组术后发生 ≥ 3 级不良事件的数量较多（39.0% 相对于试验组的 25.6%）。 两个治疗组均没有新毒性的证据。
根据试验作者, 试验的一些局限性包括参与中心主要位于北美，参与者并不能充分代表北美人口的多样性。 并未对所有参与者进行微卫星不稳定状态和 MRI 分期。此外，该研究结果并不适用于所有直肠癌患者。患有接触骨盆壁的高危肿瘤的患者需要放射治疗(没有将这一群体纳入研究中)。
Methods: This was a randomized phase III trial (PROSPECT) in which eligible patients (clinical stage T2 node-positive, T3 node-negative, or T3 node-positive rectal cancer candidates for sphincter-sparing surgery) were randomized in an open-label manner to 6 cycles of modified FOLFOX6 (experimental group) or chemoradiotherapy (control group), given 5,040 cGy over 5.5 weeks, concurrently with oral capecitabine or intravenous 5 -FU for chemotherapy. Participants in the experimental group were restaged after chemotherapy. If tumor regression was ≥ 20%, rectal surgery (total mesorectal excision) was performed, bypassing radiation therapy. Patients with poor response (tumor regression < 20%) received additional chemoradiotherapy before surgery. The primary endpoint was disease-free survival. Time to local recurrence, overall survival, complete (R0) resection rate, complete response and toxicity were secondary endpoints.
Results: From June 2012 to December 2018, 1,194 participants were randomized and 1,128 patients started treatment (585 in the experimental group and 543 in the control group). The patients’ characteristics of the two groups were well balanced. The average age was 57 years old. Tumor location was similar in the two groups (8.6 cm from the anal verge in the experimental group versus 8.5 cm in the control group, respectively). Baseline staging with pelvic MRI was performed in 84.4% of participants in both groups. The proportion of participants with clinically node-positive tumors at the time of assignment was 60.3% in the experimental group and 63.5% in the control group. Fifty-three participants (9.1%) in the trial arm received chemoradiation due to < 20% response or intolerance to FOLFOX. After 227 events and a median follow-up of 58 months, the 5-year disease-free survival rate was 80.8% in the experimental arm compared with 78.6% in the chemoradiation arm (control group) (HR 0.92, 90.2% CI [0.74 to 1.14]; stratified noninferiority P = 0.0051), meeting the noninferiority criteria. The 5-year overall survival rate was 89.5% vs 90.2% (HR 1.04, 0.74, 1.44), respectively. In addition, the complete resection rate was 98.9% vs. 97.1%; the pathological complete response rate was 21.9% vs. 24.3%; the positive radial surgical margin rate was 1.2% vs. 1.5%.
Preoperative ≥ 3 grade adverse events occurred more frequently in the experimental group (41.0% vs. 22.8%), whereas postoperative ≥3 grade adverse events occurred in a higher number in the control group (39.0% vs. 25.6% in the experimental group). There was no evidence of new toxicities in either treatment group.
According to the trial author, some limitations of the trial included that the participating centers were primarily located in North America and that the participants were not adequately representative of the diversity of the North American population. Microsatellite instability and MRI staging were not performed on all participants. In addition, the findings do not apply to all patients with rectal cancer. Patients with high-risk tumors involving the pelvic wall required radiation therapy (this group was not included in the study).
参考文献 Reference
Scgrag D et al. N Engl J Med 2023; DOI: 10.1056/NEJMoa2303269
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某些早期直腸癌病人可以避免手术
这是根据美国Memorial Sloan-Kettering 肿瘤研究中心的一项回顾性研究。从2006到2013年，共有145位病人，患有第1－3期直腸癌。所有病人先接受了放化疗，并都取得了完全缓解，即直腸指检，内窥镜和影像学检查均无肿瘤可见。其中72人接受手术治疗。73人则为随访，每3－4個月接受直腸指检和内窥镜检查，每6個月一次影象学检查。随访中位时间为3.5年。在随访组内，74％（54位）的病人肿瘤无复发而毋需手术；26％（19位）的病人需要手术，或者是因为粘膜内肿瘤复发（16位），或者是肠系膜／淋巴结复发（3位）。研究者认为手术和随访组之间，在远处转移，和总体生存率之间无显著性差异。4年疾病特异性生存率分别为91％（随访组）和96％（手术组）。 笔者认为，这项研究为某些病人提供了除手术以外另一种方案，但对随访组必须积极观察。毕竟这是一项小规模的回顾性研究。
参考文献 2015 Gastrointestinal Cancer Symposium, San Francisco. Abstract 509PD-1阻断剂单独用于错配修复缺陷 (dMMR) 局部晚期直肠癌 (3/26/2022)
PD-1 inhibitor alone used in mismatch repair deficient locally advanced rectal cancer
错配修复缺陷（dMMR）直肠肿瘤对新辅助（手术前）化疗反应不佳。 这项试验的目的是评估新辅助PD-1 阻断在 dMMR 局部晚期直肠癌中的临床益处。
方法：这是一项前瞻性、单臂、II 期研究，临床 II 期和 III 期 dMMR 直肠癌患者接受新辅助 dostarlimab（抗 PD-1）共 6 个月。共同主要目标是确定总响应率和病理完全响应或临床完全响应率，有或没有化放疗。在基线, 6 周, 3 个月和 6 个月时进行内窥镜肿瘤评估；在治疗前基线, 3 个月和 6 个月时进行成像。符合既定标准的临床完全响应患者有资格在没有化放疗的情况下进行非手术治疗。新辅助 dostarlimab 后有残留病灶的患者接受标准化放疗。化放疗后，任何未能达到临床完全响应的患者都将接受手术治疗。
结果：共纳入 13 名患者，中位年龄 52 岁（范围 26-78 岁），77% 为女性，92% 的患者经直肠 MRI 呈淋巴结阳性。在接受至少 3 个月评估的 12 名患者中，客观响应率为 100%。 7 名患者完成了诱导治疗，所有 7 名（100%）患者均达到了临床完全响应，并且正在接受未进行化放疗或手术的观察。迄今为止，疾病进展率为0%。没有患者需要化放疗或手术。没有发生严重的不良事件。
结论：在这项小型研究中, dostarlimab 单药新辅助治疗局部晚期 dMMR 直肠腺癌有效且耐受性良好，使患者避免放化疗和手术。进一步的患者招募正在进行中。
Mismatch repair deficient (dMMR) rectal tumors respond poorly to neoadjuvant (preoperative) chemotherapy. The purpose of this trial was to evaluate clinical benefit of neoadjuvant PD-1 blockade in dMMR locally advanced rectal cancer.
Methods: This is a prospective, single-arm, phase II study of patients with clinical stage II and III dMMR rectal cancer who received neoadjuvant dostarlimab (anti-PD-1) for 6 months. The co-primary objective was overall response rate and pathological complete response rate or clinical complete response rate, with or without chemoradiation. Endoscopic tumor assessments were performed at baseline, 6 weeks, 3 months, and 6 months; imaging was performed at baseline before treatment, 3 months, and 6 months. Patients who met the established criteria for a clinically complete response were eligible for nonoperative treatment in the absence of chemoradiation. Patients with residual disease after neoadjuvant dostarlimab received standardized radiotherapy. After chemoradiation, any patient who fails to achieve a complete clinical response will be treated with surgery.
Results: Thirteen patients were included, with a median age of 52 years (range, 26-78 years), 77% were female, and 92% were lymph node-positive by transrectal MRI. In 12 patients who were evaluated for at least 3 months, the objective response rate was 100%. Seven patients completed induction therapy, and all seven (100%) achieved a clinical complete response and were being observed without chemoradiation or surgery. To date, the disease progression rate was 0%. No patients required chemoradiation or surgery. No serious adverse events occurred.
Conclusions: In this small study, single-agent, Dostarlimab, neoadjuvant therapy was effective and well-tolerated in locally advanced dMMR rectal adenocarcinoma, allowing patients to avoid chemoradiotherapy and surgery. Additional patient recruitment is underway.
参考文献 Reference Lumish MA et al. J Clin Onc 2022; 40 (4)_suppl, 16