局部晚期直肠癌新辅助治疗pCR相关因素研究

目的 评价局部晚期直肠癌新辅助治疗后pCR的相关影响因素。方法 回顾分析2011—2013年间收治的265例AJCC分期Ⅱ、Ⅲ期直肠癌患者资料。所有患者均接受新辅助治疗±等待手术间期化疗, 而后手术。运用单因素和二元Logistic回归多因素分析影响pCR的预测因素, 并根据预测危险因素进行归类后分为无风险组(无因素)、低风险组(1个因素)、高风险组(2个因素)。建立临床风险评估模型。因素分析运用二元Logistic回归模型。结果 达pCR者50例(18.9%)。单因素分析中新辅助治疗前CEA、放化疗前T分期、同期放化疗结束至手术间隔时间和放化疗前肿瘤最大厚度对pCR有影响(P=0.017、0.001、0.000、0.040), 多因素分析显示新辅助治疗前CEA水平和同期放化疗结束至手术间隔时间是pCR影响因素(P=0.021、0.001), 进一步分层分析表明只有非吸烟组中新辅助治疗前低水平CEA对pCR有影响(P=0.044)。临床风险评估模型诊断pCR的敏感性为80.5%, 特异性为46.0%, AUC为0.690, 阳性预测值为35.49%, 阴性预测值为86.5%, 准确性为73.9%。结论 新辅助治疗能使部分局部晚期直肠癌患者达pCR。新辅助治疗前低水平CEA和更长的同期放化疗结束至手术间隔时间是局部晚期直肠癌新辅助治疗pCR的预测因素, 而新辅助治疗前低水平CEA对pCR预测只在非吸烟人群中有效。根据新辅助治疗前CEA>5 ng/ml和同期放化疗结束至手术间隔时间≤8周的危险因素建立的临床风险评估模型可用于预测局部晚期直肠癌新辅助治疗pCR率。     

局部晚期直肠癌术前同期放化疗达pCR者预后分析

目的 分析与局部晚期直肠癌患者术前放化疗后达pCR相关的临床因素。方法 搜集2005—2012年间经活检证实并neo-CRT (放疗采用3DCRT、VMAT)及根治性切除的临床资料完整的局部晚期直肠癌297例,采用Logistic回归模型多因素分析年龄、性别、肿瘤距肛门距离、疗前血清CEA水平、疗前血红蛋白、cT分期、cN分期与pCR是否相关。结果 全组疗后达pCR者78例(26.7%),T₁—T₃期者达42例(34.4%),T₄期者达37例(21.1%)。疗前CEA≤5.33 ng/ml疗后达pCR者55例(36.4%),CEA>5.33 ng/ml仅24例(16.4%)。单因素分析年龄、性别、肿瘤距肛门距离、疗前是否贫血和cN分期与pCR无关。多因素分析cT₁—T₃期、疗前CEA≤5.33 ng/ml是影响局部晚期直肠癌neo-CRT后是否达pCR的影响因素(P=0.031、0.000)。结论 临床分期、疗前血清CEA水平是影响局部晚期直肠癌neo-CRT后是否达pCR的影响因素;疗前血清CEA水平可作为局部晚期直肠癌neo-CRT后是否达pCR的筛选指标之一。     

Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy

PURPOSE: The aim of this study was to investigate the role of postmastectomy radiation therapy in women with breast cancer who achieved a pathologic complete response (pCR) to neoadjuvant chemotherapy. METHODS AND MATERIALS: We retrospectively identified 226 patients treated at our institution who achieved a pCR at surgery after receiving neoadjuvant chemotherapy. Of these, the 106 patients without inflammatory breast cancer who were treated with mastectomy were analyzed. The patients' clinical stages at diagnosis were I in 2%, II in 31%, IIIA in 30%, IIIB in 25%, and IIIC in 11% (American Joint Committee on Cancer 2003 system). Of the patients, 92% received anthracycline-based chemotherapy, and 38% also received a taxane. A total of 72 patients received postmastectomy radiation therapy, and 34 did not. The actuarial rates of local-regional recurrence (LRR) and survival of the two groups were compared using the log-rank test. RESULTS: The median follow-up of surviving patients was 62 months. Use of radiation therapy did not affect the 10-year rates of LRR for patients with Stage I or II disease (the 10-year LRR rates were 0% for both groups). However, the 10-year LRR rate for patients with Stage III disease was significantly improved with radiation therapy (7.3% +/- 3.5% with vs. 33.3% +/- 15.7% without; p = 0.040). Within this cohort, use of radiation therapy was also associated with improved disease-specific and overall survival. CONCLUSION: Postmastectomy radiation therapy provides a significant clinical benefit for breast cancer patients who present with clinical Stage III disease and achieve a pCR after neoadjuvant chemotherapy.     

Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients

PURPOSE: In the literature, a favorable prognosis was observed for complete pathologic response after preoperative therapy (ypCR) in patients with locally advanced rectal cancer. The aim of this study is to verify whether ypCR predicts a favorable outcome in a large series of patients. METHODS AND MATERIALS: The Gastro-Intestinal Working Group of the Italian Association of Radiation Oncology collected clinical data for 566 patients with ypCR (ypT0N0) after neoadjuvant therapy. Eligibility criteria included locally advanced rectal cancer with no evidence of metastases at the time of diagnosis, evidence of ypCR after preoperative radiotherapy +/- chemotherapy (CT). RESULTS: Median radiation dose was 50 Gy. A total of 527 patients (93%) received one of 12 different neoadjuvant CT schedules. Sphincter preservation, anteroposterior resection, and endoscopic surgery were performed in 73%, 22%, and 5% of patients, respectively. Adjuvant CT was administered to 22% of patients. Median follow-up was 46.4 months. Locoregional recurrence occurred in 7 patients (1.6%). Distant metastases occurred in 49 patients (8.9%). Overall, 5-year rates of disease-free survival, overall survival, and cancer-specific survival were 85%, 90%, and 94%, respectively. In multivariate analysis, only age and clinical stage statistically correlated with survival outcome. Adjuvant CT was still of borderline significance (worse for adjuvant CT). No relation was found between survival and neoadjuvant CT schedules. CONCLUSION: A ypCR after neoadjuvant therapy identified a favorable group of patients, even in this large series of 566 patients collected in 61 centers. Locoregional recurrence occurred only in 1.6% patients.     

局部晚期食管鳞癌新辅助放疗剂量与病理完全缓解关系分析

目的 探讨接受新辅助放化疗的局部晚期食管鳞癌患者新辅助放疗剂量与病理完全缓解(pCR)的关系。方法 收集2017-2019年间在四川大学华西医院肿瘤中心经病理确诊为食管鳞癌并接受新辅助放化疗和手术的 116例局部晚期患者临床资料。116例患者中 40~45Gy组 80例,≥45Gy组 36例,分析两组术后pCR率。结果 全组患者的pCR率为38.8%(45/116),40~45Gy组与≥45Gy组的pCR率分别为44%(35/80)和28%(10/36)(P=0.105)。结论 术前新辅助采用较高的放疗剂量不增加局部晚期食管鳞癌的pCR率,有必要进行前瞻性的临床研究确定合适的新辅助放疗剂量。     

局部晚期直肠癌术前新辅助放化疗后ypT1～4N0期患者术后辅助化疗的价值

目的 探讨局部晚期直肠癌术前新辅助放化疗后ypT1～4N0期患者术后辅助化疗的价值.方法 收集2003年3月至2010年12月间,经术前同期放化疗及根治性手术后病理检查证实为ypT1～4N0期的局部晚期直肠癌患者104例,其中术后辅助化疗73例,术后未化疗31例;ypT1～2期39例,ypT3 ～4期65例.对全组患者和亚组患者进行生存分析.结果 中位随访时间为41个月.全组104例ypT1～4N0期患者的3年总生存率和无复发生存率分别为93.4％和85.3％,其中术后辅助化疗组患者的3年总生存率和无复发生存率分别为95.5％和88.6％;术后未化疗组患者的3年总生存率和3年无复发生存率分别为88.6％和77.2％.术后辅助化疗组与术后未化疗组患者总生存曲线和无复发生存曲线的差异均无统计学意义(P值分别为0.106和0.108).术后辅助化疗组患者的3年局部复发率和远处转移率分别为4.1％(3/73)和5.5％(4/73);术后未化疗组患者的3年局部复发率和远处转移率分别为3.2％(1/31)和16.1％(5/31).术后辅助化疗组与术后未化疗组患者的局部复发差异无统计学意义(P=0.676),远处转移差异有统计学意义(P=0.030).亚组分析的结果显示,在ypT1 ～2N0期患者中,术后辅助化疗组与术后未化疗组患者的总生存曲线和无复发生存曲线的差异均无统计学意义(P值分别为0.296和0.939),术后辅助化疗组与术后未化疗组患者的局部复发和远处转移差异均无统计学意义(P值分别为0.676和0.414).在ypT3～4N0期患者中,术后辅助化疗组与术后未化疗组患者的总生存曲线和无复发生存曲线的差异均有统计学意义(P值分别为0.034和0.025).术后辅助化疗组与术后未化疗组患者的局部复发差异无统计学意义(P=0.548),远处转移差异有统计学意义(P=0.010).结论 术后辅助化疗能降低局部晚期直肠癌术前新辅助放化疗后ypT3～ 4N0期患者的远处转移率,从而改善其预后,但并不能使ypT1～ 2N0期患者的生存获益.     

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

ObjectiveThe accurate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) remains challenging. Few studies have investigated pathologic complete response (ypCR) prediction in patients with residual flat mucosal lesions after treatment. This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer (LARC).MethodsData of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital. Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed, and a nomogram was constructed by incorporating the significant predictors.ResultsOf the 246 patients with residual flat mucosal lesions included in the final analysis, 56 (22.8%) had ypCR. Univariate and multivariate analyses showed that pretreatment cT stage (pre-cT) ≤T2 (P=0.016), magnetic resonance tumor regression grade (MR-TRG) 1−3 (P=0.001) and residual mucosal lesion depth =0 mm (P<0.001) were associated with a higher rate of ypCR. A nomogram was developed with a concordance index (C-index) of 0.759 and the calibration curve showed that the nomogram model had good predictive consistency. The follow-up time ranged from 3.0 to 113.3 months, with a median follow-up time of 63.77 months. The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival (DFS) or overall survival (OS).ConclusionsCompletely flat mucosa, early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT. Endoscopic mucosal re-evaluation before surgery is important, as it may contribute to decision-making and facilitate nonoperative management or organ preservation.     

The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation

Neoadjuvant concurrent chemoradiation (CCRT) is standard treatment for clinical stage II/III rectal cancers. However, whether patients with pathological complete response (pT0N0, pCR) should receive adjuvant chemotherapy and whether delayed surgery will influence the pCR rate remains controversial. A nationwide population study was conducted using the Taiwan Cancer Registry Database from January 2007 to December 2013. Kaplan‐Meier survival analysis was performed. Cox proportional hazards models were used to estimate multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Of the 1,914 patients who received neoadjuvant CCRT, 259 (13.6%) achieved pCR and had better survival (adjusted HR: 0.37, 95% CI: 0.24‐0.58; p < 0.001). The cumulative rate of pCR rose up to 83.4% in the 9th week and slowly reached a plateau after the 11th week. Among the patients with pCR, those who received adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (adjusted HR: 0.72, 95 CI: 0.27–1.93; p = 0.52). By subgroup analysis, those younger than 70‐year old and received adjuvant chemotherapy had better survival benefit than those without adjuvant chemotherapy (adjusted HR: 0.19, 95% CI: 0.04–0.97; p = 0.046). Delayed surgery by 9–12 weeks after the end of neoadjuvant CCRT can maximize the pCR rate, which is correlated with better survival. Adjuvant chemotherapy may be considered in patients with pCR and aged <70‐year old, but further prospectively randomized controlled trials are warranted to validate these findings.     

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study

IntroductionThe addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics.MethodsAll LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics.ResultsOf 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013).ConclusionTreatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.     

A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer

Background

Pathologic complete response (pCR) to neoadjuvant chemoradiation for esophageal cancer is associated with improved outcomes. We evaluated whether a nomogram designed to predict who would have a pCR after trimodality therapy could also predict outcome after definitive chemoradiation.

Methods

Patients in this retrospective, single-institution analysis had received chemoradiation without surgery for esophageal cancer from 1998 through 2010; 333 such patients had complete information on all variables required for the pCR nomogram: sex; T status (by endoscopic sonography); tumor grade; tumor avidity on positron emission tomography (PET); and esophagogastroduodenoscopy (EGD)-directed biopsy results after chemoradiation. We used multivariate Cox regression to test potential associations between clinical outcomes [overall survival (OS), locoregional recurrence, and distant metastasis] and patient or treatment factors and the pCR nomogram score; the component variables of the nomogram were not reintroduced into the multivariate analysis.

Results

The median follow-up time for all patients (median age 66 years) was 18.2 months (30.7 months for those alive at the time of analysis). Patients with nomogram scores ≤125 (median for all patients) had significantly worse outcomes than patients with scores >125: median OS time 19.7 vs. 48.2 months; disease-free survival (DFS) time 6.1 vs. 31.1 months; locoregional failure-free survival time 17.7 months vs. not reached; and distant metastasis-free survival time 11.7 months vs. not reached (all P<0.001). Multivariate Cox regression analysis indicated that nomogram score independently predicted each survival outcome, along with other patient and disease factors.

Conclusions

The pCR nomogram score predicted survival outcomes in patients receiving definitive chemoradiation for esophageal cancer. Although this nomogram requires further validation, it may prove useful for stratifying patients for clinical trials designed to intensify treatments for patients at the highest risk of relapse.     

Epidermal growth factor receptor is a predictor of tumor response in locally advanced rectal cancer patients treated with preoperative radiotherapy

Epidermal growth factor receptor (EGFR) expression is observed in 50%–70% of colorectal carcinomas and is associated with poor prognosis. The aim of this study was to determine the EGFR expression rate in locally advanced rectal cancer and to analyze whether EGFR expression predicts tumor response to preoperative radiotherapy.

Between December 1997 and October 2000, 45 patients were included. Treatment consisted of preoperative pelvic radiotherapy and, in 21 patients, 2 courses of 5-fluorouracil leucovorin. Surgical resection was performed 4–8 weeks later. Immunohistochemistry for EGFR was determined at the preradiation diagnostic biopsy and in the resected specimens. Immunostaining was performed using EGFR monoclonal antibody (Biogenex, MU 207-UC). Immunohistochemical staining was evaluated according to extension and intensity. We defined positive staining (EGFR+) as extension of 5% or more.

Preoperative treatment resulted in pathologic complete remission in 7 patients (15%), downstaging in 13 patients (29%), and no response in 25 patients (56%). EGFR+ was observed in 29 of 45 tumors (64%) and was associated with neither clinical tumor stage nor clinical nodal stage. The overall response rate was 34% in EGFR+ patients vs. 62% in those who were EGFR− (p = 0.07). Only 1 of the 7 pathologic complete remission patients was EGFR+ (p = 0.003).

EGFR is expressed in a significant number of locally advanced rectal tumors. EGFR expression is an indicator for poor response to preoperative radiotherapy in advanced rectal carcinoma.     

Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay

Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes. This study was performed to identify actionable mutation(s) and to explain refractoriness and responsiveness to NAC. Included in this analysis were 76 patients among 397 with locally advanced breast cancer for whom a preoperative fresh-frozen paraffin-embedded tumor block was available for next-generation sequencing using AmpliSeq. The incidence of missense mutations in KRAS was much higher in patients with EF than in other groups (p < 0.01). In contrast, polymorphisms of the cMET gene were found in patients with pCR exclusively (p < 0.01).     

局部晚期直肠癌新辅助治疗后病理完全缓解者的预后分析

目的:总结局部晚期直肠癌新辅助治疗后病理完全缓解（pCR）者的长期预后,探讨术后辅助化疗的必要性。方法:回顾性分析2005年至2014年间,323例在我院进行新辅助治疗及根治性手术的局部晚期直肠癌患者的临床资料,分析pCR者的长期预后,同时比较术后辅助化疗组和术后未化疗组的预后。结果:52例（16.1%）获得pCR,其中1例患者失访;全组患者中位随访时间为53个月,全组5年无病生存率和总生存率分别为82.7%和90.9%。其中22例（43.1%）患者接受术后辅助化疗,29例（56.9%）未接受术后化疗。两组患者的性别、年龄、肿瘤临床分期、肿瘤位置、大小、分化程度、术前CEA水平、新辅助化疗的方案、新辅助治疗结束至手术的间隔周期、手术方式、术后并发症、淋巴结清扫的数目以及随访时间均无统计学差异。两组患者的5年无病生存率以及总生存率亦无统计学差异。结论:局部晚期直肠癌新辅助治疗后病理完全缓解者可获得良好的生存预后;对于pCR者,实施术后辅助化疗不会影响其预后。     

Oncologic benefit of adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and curative surgery with selective lateral pelvic lymph node dissection: An international retrospective cohort study

IntroductionIntensive local treatment comprising total mesorectal excision (TME) with selective lateral pelvic lymph node dissection (LPND) after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) has received attention among clinicians treating rectal cancer. It remains unclear whether adjuvant chemotherapy (ACT) after intensive local treatment is beneficial for these patients. We evaluated the oncologic benefit of ACT for patients with LARC who received intensive local treatment.Materials and methodsThis international multicentre retrospective cohort study included 737 patients treated in Japan and Korea between 2010 and 2017. The effectiveness of ACT on recurrence-free survival (RFS) was evaluated using univariable and multivariable Cox proportional hazards models, with subgroup analyses to identify subpopulations potentially benefiting from ACT.ResultsThe median follow-up was 49 months; the 5-year RFS and local recurrence rates for the entire cohort were 72.1% and 4.9%, respectively; 514 patients (69.7%) received adjuvant chemotherapy, without an oncologic benefit (hazard ratio, 1.14; 95% confidence interval [CI]: 0.79–1.68) demonstrated in the multivariable Cox regression analysis. In subgroup analyses, the distributions of the 95% CI in patients aged ≥70 years and those with ypStage 0 tended to place a disproportionate emphasis that favoured the non-ACT treatment strategy.ConclusionDespite achieving good local control with intensive local treatment strategy, the effectiveness of ACT for the LARC patients with CRT followed by TME with selective LPND was not proved. Elderly patients and those with ypStage0 may not receive benefit from ACT after CRT and TME ± LPND.     

Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy

BACKGROUND:

In a retrospective study of Southwestern Oncology Group (SWOG)‐S8710/INT‐0080 (radical cystectomy [RC] alone vs 3 cycles of neoadjuvant chemotherapy [NC] with methotrexate, vinblastine, doxorubicin, and cisplatin before RC for bladder cancer), factors found to be associated with improved overall survival (OS) included pathologic complete response, defined as P0; treatment with NC; completion of RC with negative surgical margins; and ≥10 pelvic lymph nodes (LNs) removed.

METHODS:

The authors used stratified Cox regression to retrospectively study the association of quality of pathologic response after RC with OS in the subset of S8710 patients who received NC and RC with negative surgical margins.

RESULTS:

Of 154 patients who received NC, 68 (44.2%) were <P2 (P0, Pa, P1, or carcinoma in situ [CIS]) at RC, 46 (29.9%) were P0, and the remainder had P2+ disease or did not undergo RC. In 115 patients who had RC with negative surgical margins, compared with P0 patients, those with residual Pa, P1, or CIS appeared to have worse OS (P = .054); OS was significantly worse for patients with residual P2+ disease (P = .0006). LN–positive (LN+) disease was found to be associated with worse OS than LN–negative (LN?) disease (P = .0005). Patients with LN? disease (ie, those with <10 LNs removed) appeared to have inferior OS compared with those with 10+ LNs removed (P = .079). The combination of pre‐NC clinical stage and post‐RC pathologic stage was found to be predictive of OS (P < .0001).

CONCLUSIONS:

NC and RC with negative surgical margins for bladder cancer followed by pathologic P0 and LN? disease were found to correlate with improved OS. A combination of baseline clinical stage and post‐RC pathologic stage may better predict OS. Cancer 2009. © 2009 American Cancer Society.     

局部进展期直肠癌新辅助化疗后病理完全缓解及肿瘤降期的预测因素分析

目的:探索局部进展期直肠癌(LARC)经新辅助化疗后病理完全缓解(pCR)和肿瘤降期(ypT0-1)的预测因素.方法:回顾性分析71例经新辅助化疗后进行全直肠系膜切除术的局部进展期直肠癌患者的临床资料,分析其临床特征,筛选经新辅助化疗后达到pCR及肿瘤降期(ypT0-1)的预测因子.结果:单因素分析结果显示肿瘤占肠腔<...     

Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.