Gaedcke J, Liersch T, Hess C, Becker H, Rödel C, Ghadimi B M
Universitätsmedizin Göttingen, Allgemein- und Viszeralchirurgie, Robert-Koch-Strasse 40, Göttingen, Germany.
Zentralbl Chir. 2011 Aug;136(4):334-42. doi: 10.1055/s-0031-1271581. Epub 2011 Aug 23.
Preoperative 5-fluorouracil-based radiochemotherapy (RCT) followed by quality assessed total mesorectal excision (TME surgery) are the two most important elements of multimodal treatment for patients with locally advanced rectal cancer (UICC stages II and III). The optimum sequence of these neoadjuvant modalities complemented by adjuvant (postoperative) chemotherapy, has been addressed in several randomised trials. Especially within the trials of the German Rectal Cancer Study Group (GRCSG), preoperative RCT has been shown to be superior to postoperative treatment for a variety of endpoints (pathologically confirmed complete tumour remission (pCR), RCT-induced tumour regression, R0 resection rates (including circumferential resection margins) and long-term locoregional control). This neoadjuvant multimodal strategy has decreased the 5-year and 10-year local recurrence rates below 10%, and the development of distant metastases (e.g., 35% to 45% liver metastases) remains the predominant reason for failure. Furthermore, approximately 25% of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal or the investigator's discretion. Thus, today, integrating more effective systemic therapy into (preoperative) multimodal regimens is the most accepted challenge! But from the clinical point of view this demand is also a dilemma. The question to be addressed is how and when to apply intensified systemic therapy with adequate dosage and intensity as well as acceptable treatment-associated toxicity. The increase of therapeutic options requires valid predictive biomarkers that may help to stratify patients into regimens associated with low toxicity (5-FU monotherapy alone) or into more intensified treatment for better long-term outcome. In summary, the use of biomarkers for individualised risk-adapted treatment is one of the most promising areas of clinical investigations, not only in rectal cancer. The assessment of individual tumour response, toxicity, and prognosis during multimodal treatment of rectal cancer as a model of a very common solid tumour offers radiooncologists, surgeons, pathologists, gastroenterologists as well as oncologists immense insights into the under-standing of tumour biology.
术前基于5-氟尿嘧啶的放化疗（RCT），随后进行质量评估的全直肠系膜切除术（TME手术），是局部晚期直肠癌（UICC II期和III期）患者多模式治疗的两个最重要要素。这些新辅助治疗方式与辅助（术后）化疗相结合的最佳顺序，已在多项随机试验中得到探讨。特别是在德国直肠癌研究组（GRCSG）的试验中，术前RCT在多种终点指标（病理证实的肿瘤完全缓解（pCR）、RCT诱导的肿瘤退缩、R0切除率（包括环周切缘）和长期局部区域控制）方面已被证明优于术后治疗。这种新辅助多模式策略已将5年和10年局部复发率降低至10%以下，远处转移的发生（如35%至45%的肝转移）仍然是主要的失败原因。此外，约25%的患者未接受辅助化疗，主要是由于手术并发症、患者拒绝或研究者的判断。因此，如今将更有效的全身治疗纳入（术前）多模式方案是最公认的挑战！但从临床角度来看，这一需求也是一个两难境地。需要解决的问题是如何以及何时应用剂量和强度合适且治疗相关毒性可接受的强化全身治疗。治疗选择的增加需要有效的预测生物标志物，这可能有助于将患者分层为与低毒性方案（单独使用5-FU单药治疗）相关的方案，或分层为更强化的治疗方案以获得更好的长期疗效。总之，使用生物标志物进行个体化风险适应性治疗是临床研究最有前景的领域之一，不仅在直肠癌中如此。作为一种非常常见的实体瘤模型，在直肠癌多模式治疗期间评估个体肿瘤反应、毒性和预后，为放射肿瘤学家、外科医生、病理学家、胃肠病学家以及肿瘤学家提供了对肿瘤生物学理解的深刻见解。
