2010 NCCN Clinical Practice Guidelines for Colorectal Cancer
At the 3rd NCCN Asian Academic Meeting, NCCN Board Chairs, Professor Benson of Northwestern University (USA) and Professor Venook of the University of California (USA), presented the main points of updates to the 2010 edition of the NCCN Clinical Practice Guidelines for Colorectal Cancer. Zhang Mao, Department of General Surgery, Baotou Central Hospital Adjuvant therapy for stage II colon cancer In principle, the risk assessment for stage II colon cancer was revised to include: if fluorouracil-based monotherapy is considered, mismatch repair (MMR) testing is recommended; patients with stage II colon cancer with high microsatellite instability (MSI-H) may have a good prognosis and cannot benefit from adjuvant therapy with 5-FU. In the principles of adjuvant therapy, revision of bevacizumab, cetuximab, panitumumab or irinotecan should not be used for adjuvant chemotherapy in patients with stage II or III disease, unless a clinical trial is being conducted.Professor Benson noted that adjuvant therapy for stage II colon cancer is most controversial and it remains unclear which patients do need adjuvant therapy. Current retrospective studies on molecular prognostic factors suggest that there may be a group of stage II patients at high risk of recurrence, but prognostic markers identifying these patients have not been confirmed in prospective trials. One of the interesting molecular prognostic factors is mismatch repair deficiency (dMMR). A study showed that MMR protein detected by immunohistochemistry (IHC) and microsatellite instability (MSI) detected by PCR revealed two manifestations of colon cancer biotype, i.e. dMMR corresponding to MSI-H and mismatch repair normal (pMMR) corresponding to low microsatellite instability/microsatellite stability (SIL/MSS). a retrospective study in 2003 suggested that A 2008 study showed that dMMR was a predictive marker of ineffectiveness of adjuvant 5-FU treatment for colon cancer, and a 2008 meta-analysis also showed that in stage II patients, those with dMMR did not have a survival advantage over untreated patients with adjuvant chemotherapy and had a significantly shorter 5-year DFS (72% vs. 87%). The 5-year DFS was significantly shorter (72% vs 87%). However, another large study, QUASAR, showed an absolute benefit of 3-4% in patients with stage II colon cancer treated with adjuvant 5-FU/LV compared with surgery alone and showed that recurrence score, T-stage and dMMR were key independent predictors of recurrence in stage II colon cancer, but unfortunately, models based on efficacy-related genes failed to predict the efficacy of adjuvant 5-FU/LV. The results of these studies have been very positive. Professor Benson emphasized that these findings suggest that adjuvant chemotherapy with 5-FU in stage II patients with dMMR may not provide a survival benefit but may be detrimental to patients, but the current study is a small retrospective study and the results must be further confirmed in a prospective study. Local excision for rectal cancer An important update in the new guidelines is that transanal resection is recommended for patients with stage T1 tumors, and is no longer recommended for the initial treatment of patients with stage T2 disease, according to Prof. Venook. An American College of Surgeons Oncology Group (ACOSOG) Z6041 study was designed to evaluate the regression of patients with stage T2N0 rectal cancer treated with neoadjuvant chemoradiotherapy followed by local excision; however, patients were lost to local excision due to the toxic effects of concurrent chemoradiotherapy. The study also ended prematurely in November 2009. Neoadjuvant chemotherapy for rectal cancer Any T, any N, M1 patient with concurrent resectable metastases is recommended to be given 2-3 months of combination chemotherapy, followed by radiotherapy or staged (or concurrent) resection of metastases and primary site after evaluation. Recommended combination chemotherapy regimens include FOLFIRI/FOLFOX/CapeOX±bevacizumab, FOLFIRI/FOLFOX±cetuximab/panitumumab (KRAS wild type only). 2010 A study showed that 14 patients with stage II/III rectal cancer treated with neoadjuvant chemotherapy without radiotherapy had a pCR of 36%. Another study showed that 29 patients with stage II/III rectal cancer treated with neoadjuvant chemotherapy without pelvic radiotherapy had an R0 resection rate of 100% and a pCR of 27%. Based on these findings, ACOSOG/CALGB 81001 proposed that for patients with T1-2N1 and T3N0-1 suitable for anus-preserving surgery, FOLFOX neoadjuvant chemotherapy could be given for 6 cycles and then re-evaluated, followed by chemoradiotherapy followed by total mesenteric rectal radical excision (TME) if the patient has disease progression, or TME if the patient has no disease progression, with the ultimate goal The ultimate goal is to achieve R0 resection in more than 90% of patients. Summary of key points of the guideline update: 1. Adjuvant therapy for stage II colon cancer Principles of risk assessment for stage II colon cancer: MMR testing is recommended if fluorouracil-based monotherapy is considered; patients with stage II colon cancer with MSI-H, who may have a good prognosis, do not benefit from adjuvant therapy with 5-FU. Bevacizumab, cetuximab, panitumumab or irinotecan should not be used for adjuvant chemotherapy in patients with stage II or III disease, unless a clinical trial is performed. 2. local excision for rectal cancer transanal resection is recommended for patients with stage T1 tumors and is no longer recommended for the initial treatment of patients with stage T2. 3. neoadjuvant chemotherapy for rectal cancer Any T, any N, M1 patient with concurrent resectable metastases is recommended to be given 2-3 months of combination chemotherapy, followed by radiotherapy or staged (or concurrent) resection of the metastases and primary site after evaluation. Recommended combination chemotherapy regimens include: FOLFIRI/FOLFOX/CapeOX±bevacizumab, FOLFIRI/FOLFOX±cetuximab/panitumumab (KRAS wild type only).