Search

Importance: Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown., Objectives: To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy., Design, Setting, and Participants: This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022., Interventions: Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine., Main Outcomes and Measures: The primary end point was pathologic complete response rate., Results: Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy., Conclusions and Relevance: This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

Purpose: We compared the long-term outcome of the watch and wait (WW) strategy and surgery in patients with locally advanced rectal cancer., Patients and Methods: This prospective cohort study included 84 patients who achieved clinical complete response (cCR) after neoadjuvant chemoradiotherapy (NCRT). They were divided into the WW group (n = 58) and surgery group (SG, n = 26). Patients in the SG underwent total mesorectal excision. The study site was the Peking University Cancer Hospital., Results: Eighty-four patients were included (58 and 26 in the WW group and SG, respectively). A total of 76·9% of the patients in the SG achieved pathological complete response (pCR) and 23·1% of the patients had a residual tumor. The total recurrence and metastasis rate was 15·4% (4/26) in the SG and 18·9% (11/58) in the WW group. There was no significant difference in the recurrence and metastasis rate between the two groups. In the WW group, 9 cases developed tumor regrowth during follow-up and underwent salvage surgery. The overall survival rate of the WW group (96·6% vs 92·3%) was not significantly different from that of the SG (P > 0·05). The WW patients also retained their anal sphincter function and avoided surgery-related complications., Conclusion: The WW strategy is a feasible treatment option in patients with cCR after NCRT. Surgery may not bring benefits to these cCR patients., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Distant metastasis has been the major concern of prognosis in patients with locally advanced rectal cancer (LARC). The purpose of this study was to investigate the prognostic value of TMB in blood (bTMB) in LARC patients after receiving neoadjuvant chemoradiotherapy (nCRT) and surgery. Using targeted ctDNA sequencing, we revealed that bTMB level at baseline was positively correlated with recurrence-free survival (RFS). Following nCRT, the patients with decreasing TMB tends to have a longer median RFS. bTMB level after surgery was negatively correlated with RFS. The serum cytokines including IFNγ, IFNα2, IL-1β, IL-2 and MIP-1β were significantly higher in pre-nCRT serum with higher bTMB group than that of lower bTMB group. Clonal evolution analysis showed that the pre- and post-nCRT ctDNAs of most cases had shared mutations. In conclusion, we presume that bTMB could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the clinical and oncological outcomes of selected rectal cancer patients with massive stoma site tumors who underwent radical resection and reconstruction., Methods: We reviewed 8 cases of massive stoma site tumors in patients who had permanent gastrointestinal stoma in the abdominal wall following radical resection of rectal cancer between March 2013 and May 2018 at the Peking University Cancer Hospital and Peking University Shougang Hospital., Results: There were seven males and one female patient, with a median age of 50.6 years. The average time between the initial surgery and the development of a malignant tumor at the stoma site was 5 years (range, 0.5-14 years). The average diameter of the stoma site tumors was 8.1 cm, and the diameter of the largest tumor was 12 cm. After tumor resection, the area of the largest abdominal wall defect was about 15 × 14 cm 2 . Abdominal wall repair included the use of a tensor fasciae latae muscle flap, local fasciocutaneous rotational flap, and pedicled anterolateral thigh flap. No patient died in the 30 days following surgery. The longest follow-up period was 81 months, and 5 patients died., Conclusions: Multidisciplinary clinical management fosters positive outcomes in treating massive stoma site tumors. Local R0 resection and abdominal wall reconstruction are safe and feasible, and function to removes local disease, allowing patients to live a higher quality of life., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross - sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher's exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions: Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.

Objective: To investigate the long-term outcome of organ preservation with local excision or "watch and wait" strategy for mid-low rectal cancer patients evaluated as clinical complete remission (cCR) or near-cCR following neoadjuvant chemoradiotherapy (NCRT)., Methods: Clinical data of 62 mid-low rectal cancer patients evaluated as cCR/near-cCR after NCRT undergoing organ preservation surgery with local excision or receiving "watch and wait" strategy at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from March 2011 to August 2017 were retrospectively analyzed. According to the approximate 1:2 pairing, 123 patients who underwent radical resection with complete pathological remission(ypCR) after neoadjuvant chemotherapy during the same period were selected for prognosis comparison. The primary endpoint of the study was 3-year non-regrowth disease-free survival (NR-DFS) and tumor specific survival (CSS). Survival analysis was performed using the Kaplan-Meier curve (Log-rank method). The secondary endpoint of the study was 3-year organ preservation and sphincter preservation., Results: The retrospective study included 38 male and 24 female patients. The median age was 60 (31-79) years and the median distance from tumor to anal verge was 4(1-8) cm. The ratio of cCR and near-cCR was 79.0%(49/62) and 21.0%(13/62) respectively. Local regrowth rate was 24.2%(15/62). Of 15 with tumor regrowth, 9 patients received salvage radical rectal resection and no local recurrence was found during follow-up; 4 patients received salvage local excision among whom one patient had a local recurrence occurred patient; 2 patients refused further surgery. The overall metastasis rate was 8.1%(5/62), including resectable metastasis(4.8%,3/62) and unresectable metastasis (3.2%,2/62). The valid 3-year organ preservation rate and sphincter preservation rate were 85.5%(53/62) and 95.2%(59/62) respectively. The median follow-up was 36.2(8.6-89.0) months. The 3-year NR-DFS of patients with cCR and near-cCR was 88.6% and 83.1% respectively, which was not significantly different to that of patients with ypCR (94.7%, P=0.217). The 3-year CSS of patients with cCR and near-cCR was both 100%, which was not significantly different to that of patients with ypCR(93.4%, P=0.186)., Conclusions: Mid-low rectal cancer patients with cCR or near-cCR after NCRT undergoing organ preservation with local excision or receiving "watch and wait" strategy have good long-term prognosis with low rates of local tumor regrowth and distant metastasis, which is similar to those with ypCR after radical surgery. This treatment mode may be used as an option for organ preservation in mid-low rectal cancer patients with good tumor remission after NCRT.

Checkpoint blockade therapy triggers tumor-specific immune responses in a variety of cancer types. We presumed that rectal cancer patients could have become sensitive to immunotherapy after receiving neoadjuvant chemoradiotherapy (nCRT). In this study, we report immune alternation in post-nCRT patients compared with pretreatment conditions from gene-expression omnibus (GEO) data. Whole-exome sequencing of 14 locally advanced rectal cancer (LARC) patient samples showed that nCRT induced new mutations compared with the paired pretreatment biopsies, evidenced by appearance of a neoantigen landscape. An association was identified between mutation burden and enrichment of immune activation-related pathways. Animal experiment results further demonstrated that radiotherapy enhanced the efficacy of anti-PD-1. Mutation burden and the neoantigens of LARC patients were associated with response to nCRT. The mRNA expression profiling of 66 pretreatment biopsy samples from LARC patients showed that immune activation-related pathways were enriched in response to nCRT . PD-L1 expression was negatively correlated with disease-free survival in the CD8-low expression patient group who received nCRT in a cohort of 296 samples. Thus, nCRT was able to alter immune function in LARC patients, which may be associated with the appearance of neoantigens. Neoantigens could make rectal cancer patients potential candidates to receive checkpoint blockade immunotherapy, and mutation burden could be a useful biomarker to stratify patients into responding and nonresponding groups for immunotherapy. Cancer Immunol Res; 6(11); 1401-16. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Objective: To examine the association of preoperative carcinoembryonic antigen (CEA) level with the efficacy of neoadjuvant radiochemotherapy and postoperative metastasis and relapse in patients with rectal cancer., Methods: Between January 2011 and January 2014, 325 patients with local advanced rectal cancer underwent preoperative radiochemotherapy and radical operation in Department of Colorectal Cancer Surgery, Beijing University Cancer Hospital, including 194 males and 131 females. According to preoperative MRI, all the patients suffered from clinical T3-4 tumors or positive lymph nodes. Their Zubrod-ECOG-WHO score was 0-1. These patients received preoperative intensity modulated radiotherapy which consisted of 50.6 Gy in 22 fractions (IMRT GTV 50.6 Gy/CTV 41.8 Gy/22 f) with capecitabine(825 mg/m 2 , twice per day) as radiosensitizer. According to the preoperative serum CEA level, patients were divided into high group (125 cases) and normal group (200 cases). In high group, serum CEA level decreased into normal range in 60 patients (high-normal group) after radiochemotherapy, while it was still in high level in other 65 patients (high-high group). The differences in sensitivity to radiochemotherapy and 3-year disease free survival (DFS) of these patients were both evaluated., Results: In high group and normal group, the complete response rates were 18.4% (23/125) and 17.5% (35/200) (χ 2 =0.319, P=0.660); the percentages of tumor regression grade(TRG) 0-1 patients were 68.0%(85/125) and 67.5%(135/200)(χ 2 =0.009, P=0.925); the T downstage rates were 63.2%(79/125) and 70.0%(140/200)(χ 2 =1.266, P=0.274), respectively, whose differences were all not significant. The 3-year DFS rate in high group was 62.4%, which was significantly lower than 93.5% in normal group (χ 2 =53.147, P=0.000). There were 65 patients in high-high group, accounting for 52% (65/125) of high group. Among these 65 patients, 44(67.7%) presented recurrence and metastasis within 3 years and the 3-year DFS was 32.3%, which was much lower than 95.0% of 60 patients in high-normal group(χ 2 =182.085, P=0.000)., Conclusions: Preoperative serum CEA level may not be used to predict tumor response of rectal cancer patients who receive preoperative radiochemotherapy. However, the prognosis of patients with high CEA level is worse. Recurrence and metastasis are more likely to occur in patients with high CEA level after radiochemotherapy.

Objective: To investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT)., Method: From March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years., Results: A total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%., Conclusions: Organ preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.

The aim of the study was to investigate the prognostic value of pigment epithelium-derived factor (PEDF) in locally advanced rectal carcinoma (LARC) treated with neoadjuvant radiation therapy (nRT). The level of PEDF expressing was examined in LARC tissues treated with nRT by immunohistochemistry and the prognostic significance of PEDF was analysed by univariate and multivariate survival analyses. We forced expression of PEDF in highly metastatic LoVo cells. The clonogenic survival assay was used to test the cellular sensitivity to radiation. Wound healing and Boyden chamber assays were used to detect cell migration and invasion. To assess the contribution of PEDF in vivo, we established tumor xenografts. The mechanisms of PEDF on cancer cells was analysed by bioinformatics. Our immunohistochemical staining of tissue samples revealed that prolonged DFS (77.1 vs 49.0%) and OS (87.1 vs 56.3%) was observed in PEDF-positive cases (P<0.001) following nRT. PEDF could be an independent factor for DFS [P=0.001; HR, 0.422 (95% CI, 0.249-0.717)] and OS [P=0.003; HR, 0.418 (95% CI, 0.234-0.749)]. Positive-expression of PEDF was negatively correlated with tumor differentiation (P<0.016), ypT stage (P<0.037), ypTNM stage (P<0.033), and ypN stage (P=0.006). Overexpression of PEDF in high metastatic cells enhanced radiosensitivity and, suppressed migration and invasion in vitro. In tumor xenografts, PEDF significantly suppressed tumor growth. Furthermore, by bioinformatics analysis, we found PEDF performs functions via activating P53 to regulate double-strand break repair pathway and activate the G protein activation pathway. Our findings indicate that PEDF was identified as a predictive candidate for nRT responsiveness. These findings may be used to stratify LARC patients and make alternative strategies for adjuvant treatment.

Objective: To investigate the survival and prognostic factors of stage 0 to III rectal cancer in 10 years., Methods: Clinical data and follow-up of 856 rectal cancer patients with stage 0-III underwent curative surgery from January 2000 to December 2010 were retrospective analyzed. There were 470 male and 386 female patients, with a mean age of (58 ± 12) years. Kaplan-Meier method was used to analyze the overall survival and disease free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to analyze the independent prognostic factors of rectal cancer., Results: The patients in each stage were stage 0 with 18 cases, stage I with 209 cases, stage II with 235 cases, and stage III with 394 cases. All patients received curative surgery. There were 296 patients evaluated as cT3, cT4 and any T with N+ received preoperative radiotherapy. 5.4% patients got pathological complete response (16/296), and the recurrence rate was 4.7% (14/296). After a median time of 41.7 months (range 4.1 to 144.0 months) follow-up, the 5-year overall survival rate in stage 0 to I of was 91.0%, stage II 86.2%, and stage III 60.0%, with a significant difference (P=0.000). The cumulative local recurrence rate was 4.8% (41/856), of which 70.7% (29/41) occurred within 3 years postoperatively, 97.6% (40/41) in 5 years. The cumulative distant metastasis rate was 16.4% (140/856), of which 82.9% (129/140) occurred within 3 years postoperatively, 96.4% (135/140) in 5 years. The incidence of abnormal imaging findings was significantly higher in pulmonary than liver and other sites metastases (75.0% vs. 21.7%, χ² =25.691, P=0.000). The incidence of CEA elevation was significantly higher in liver than lung and other sites metastases (56.8% vs. 37.8%, χ² =25.691, P=0.000). Multivariable analysis showed that age (P=0.015, HR=1.385, 95% CI: 1.066 to 1.801), surgical approach (P=0.029, HR=1.337, 95% CI: 1.030 to 1.733), differentiation (P=0.000, HR=1.535, 95% CI: 1.222 to 1.928), TNM stage (P=0.000, HR=1.349, 95% CI: 1.260 to 1.444) and lymphovascular invasion (P=0.001, HR=1.715, 95% CI: 1.258 to 2.342) are the independent prognostic factors for rectal cancer., Conclusions: Age, surgical approach, differentiation, TNM stage and lymphovascular invasion are independent prognostic factors for rectal cancer. Preoperative evaluation and combined modality therapy can significant reduce the local recurrence and improve overall survival for rectal cancer patients.

Background: In China, standard neoadjuvant chemoradiation therapy has not been well accepted, not only because of financial constraints but also because of the poorly-tolerated long duration of the regimen., Objective: The current study aimed to evaluate the impact of a modified neoadjuvant radiation regimen on the prognosis of rectal cancer patients in China., Design: This was a nonrandomized cohort study evaluating outcomes of patients who chose to undergo preoperative radiotherapy compared with those who chose not to undergo preoperative radiotherapy (controls)., Settings: The study was carried out in Peking University Cancer Hospital, a tertiary care cancer center in China., Patients: Records of patients with locally advanced, mid-to-low rectal cancer who underwent total mesorectal excision at Peking University Cancer Hospital from 2001 through 2005 were analyzed in this study., Intervention: Patients who chose preoperative radiotherapy received a total dose of 30 Gy delivered in 10 once-daily fractions of 3.0 Gy each, with at least a 14-day delay of surgery after delivery of the last fraction., Main Outcome Measures: Tumor downstaging was evaluated. Local recurrence, distant metastases, and disease-free and overall survival were analyzed with the Kaplan-Meier method., Results: A total of 101 patients accepted and 162 patients declined the modified preoperative radiotherapy regimen. Of the 101 patients receiving preoperative radiotherapy, 5 (5%) had a complete response, and 50 (50%) achieved TNM downstaging. The local recurrence rate was 5% with preoperative radiotherapy and 18% in the control groups (p = 0.02). Within the preoperative radiotherapy group, 5-year disease-free survival and overall survival rates were significantly higher in patients with T-, N-, or TNM-downstaging than in patients without downstaging. Evaluation of literature reports indicated that clinical safety and effectiveness of the modified protocol are comparable to results of standard neoadjuvant procedures., Limitations: The allocation to study groups was not randomized, and patient self-selection may have introduced bias, particularly because patients with greater financial means were more likely to choose to undergo the preoperative radiotherapy regimen., Conclusions: Compared with surgery alone, this modified preoperative radiotherapy regimen is associated with significantly reduced local recurrence and complication rates, with improved survival in patients who show downstaging. The modified protocol offers a clinical outcome equivalent to standard preoperative radiotherapy regimens while offering an alternative for increasing the flexibility of preoperative radiation regimens in China.

Background: Great changes have occurred in the management of rectal cancer. This study presents the outcome of total mesorectal excision (TME) for rectal cancer in a single Chinese institution and evaluates TME's role in the comprehensive management of rectal cancer., Methods: We reviewed the data of rectal cancer patients surgically treated by three colorectal surgeons from January 2000 to August 2004. Patients who received surgical resection for rectal cancer from January 1996 to December 1999, before the introduction of TME, were chosen as controls. Data regarding characteristics of patients and tumors, surgical procedures, postoperative complications, and results of follow-up were collected for analysis., Results: Three hundred and seventy-seven patients with rectal cancer were enrolled in our study, with 175 patients in the TME group and 202 as controls. Mortality and morbidity rates were 1% and 14% in TME patients and 1% and 31% in controls, respectively. The TME group had a shorter operation time and hospital stay, and less bleeding, wound and urinary complications. The local recurrence (LR) rate was 6% and 12% in the TME and the control groups, respectively (P<0.05). With a median follow-up of 35 months, the actuarial 5-year survival rate was 66%. Consistent with the univariate analysis result, multivariate analysis demonstrated that TNM stage, tumor grade, age, and surgeons were independent prognostic factors. TME was not an independent prognostic factor for patients' survival., Conclusions: TME is a safe and efficient option in reducing LR. However, it is not an independent predictor for patients' survival. In addition to the standardized usage of TME, further knowledge on the molecular mechanism of cancer is needed.