local excision ( le ) techniques for rectal cancer are appealing due to their lower perioperative morbidity and mortality rates and better functional outcomes compared with standard transabdominal resection . however , le with curative intent is currently recommended for strictly selected t1 rectal cancers with favorable features such as < 30% rectal circumference , <3 cm in size , mobile , non - fixed , within 8 cm of the anal verge , well to moderately differentiated , and no evidence of lymphadenopathy on pretreatment imaging . although several studies have reported the treatment results of le for patients with ct2 tumors , le has not gained widespread acceptance due to disappointing outcomes even with adjuvant therapy . for more advanced tumors , le should be restricted to palliative purposes only . in the era of preoperative chemoradiotherapy ( crt ) , the potential advantages of preoperative crt have increased interest in the use of le for patients with locally advanced rectal cancer ( larc ) who show significant tumor regression after preoperative crt . several retrospective studies have reported the treatment outcomes of le for a highly select subset of patients with ct2 - 3 rectal cancer who respond well to preoperative crt . however , most reported data were limited by being assessed in only a few single - center studies involving relatively small numbers of patients with favorable features . the american college of surgeons oncology group ( acosog ) trial z6041 recently published preliminary results of preoperative crt and le for ct2n0 rectal cancer . in addition , the capecitabine , radiotherapy and transanal endoscopic microsurgery surgery ( carts ) study , which will investigate the feasibility of preoperative crt followed by transanal endoscopic microsurgery in patients with ct1 - 3n0 rectal cancer , is currently recruiting participants . however , retrospective series or clinical trials regarding clinical experience with the use of preoperative crt and le for larc are sparse . this study investigated the treatment outcomes of le following preoperative crt for patients with ct3 - 4 rectal cancer who refused ablation of the anal sphincter , were considered inoperable due to medical comorbidities that contraindicated a major surgery , or achieved good response to preoperative crt . the patient database was reviewed to select patients with larc who received preoperative crt followed by le . all patients were required to meet the following inclusion criteria for entry into the study : 1 ) histologically confirmed rectal adenocarcinoma , 2 ) ct3 - 4 classification , 3 ) no distant metastasis , and 4 ) the initiation of preoperative crt before september 30 , 2009 . eight korean radiation oncology centers participated in the data collection , and a total of 27 patients were registered . one was when the doctor recommended le as the primary option limited to clinical complete response ( cr ) patients . the other was when the doctor recommended the procedure as an alternative to radical surgery due to refusal of radical surgery , old age , medical inoperability , etc . in the case of the former , the patient showing clinical cr following preoperative crt would have given his or her consent to an experimental treatment after being sufficiently informed . this study was approved by the institutional review board of the national cancer center , republic of korea ( nccncs-12 - 649 ) and the korean radiation oncology group ( krog 12 - 04 ) . preoperative radiation therapy was given to a dose of 44.0 to 50.4 gy ( median , 50.4 gy ) in 1.8 to 2.0 gy daily fractions . conventional or three - dimensional treatment planning using three- or four - field techniques was used . chemotherapy was administered concurrently with radiation therapy using a fluoropyrimidine - based regimen ( n=23 , 85% ) or irinotecan - based regimen ( n=4 , 15% ) . four to 8 weeks after completion of preoperative crt , le was performed by a transanal approach under general anesthesia . nineteen patients ( 70% ) received adjuvant chemotherapy comprising a fluoropyrimidine - based regimen ( n=18 , 67% ) or oxaliplatin - based regimen ( n=1 , 4% ) . the chemotherapeutic regimens , both preoperative and postoperative , were selected for each patient according to the preferences of the attending medical oncologists . all patients underwent a standard pretreatment workup including medical history , physical examination , serum carcinoembryonic antigen level , and imaging studies including chest x - ray and computed tomography ( ct ) , transrectal ultrasonography , f - fluorodeoxyglucose positron emission tomography , or magnetic resonance imaging . the response to preoperative crt was evaluated using the tumor regression grading system proposed by dworak et al . . tumor regression was graded as follows : grade 0 , no regression ; grade 1 , minimal regression ; grade 2 , moderate regression ; grade 3 , near - complete regression ; and grade 4 , complete regression . all tumors were staged according to the american joint committee on cancer staging manual 7th edition . all patients underwent standardized follow - up comprising a physical examination , digital rectal examination , complete blood counts , biochemical profiles , and serum carcinoembryonic antigen level at each visit . follow - up imaging studies , such as abdominopelvic ct and colonoscopy , were performed as clinically indicated or at the physician 's discretion . disease recurrence was pathologically proven by surgical resection , biopsy , or cytology and/or radiological findings . the primary endpoint was relapse - free survival ( rfs ) , defined as the time interval from the initiation of crt to any type of recurrence other than death . local failure was defined as any disease recurrence within the pelvis , and any failure outside the pelvis was classified as a distant metastasis . survival was estimated using the kaplan - meier method , with differences compared using the log - rank test . the patient database was reviewed to select patients with larc who received preoperative crt followed by le . all patients were required to meet the following inclusion criteria for entry into the study : 1 ) histologically confirmed rectal adenocarcinoma , 2 ) ct3 - 4 classification , 3 ) no distant metastasis , and 4 ) the initiation of preoperative crt before september 30 , 2009 . eight korean radiation oncology centers participated in the data collection , and a total of 27 patients were registered . one was when the doctor recommended le as the primary option limited to clinical complete response ( cr ) patients . the other was when the doctor recommended the procedure as an alternative to radical surgery due to refusal of radical surgery , old age , medical inoperability , etc . in the case of the former , the patient showing clinical cr following preoperative crt would have given his or her consent to an experimental treatment after being sufficiently informed . this study was approved by the institutional review board of the national cancer center , republic of korea ( nccncs-12 - 649 ) and the korean radiation oncology group ( krog 12 - 04 ) . preoperative radiation therapy was given to a dose of 44.0 to 50.4 gy ( median , 50.4 gy ) in 1.8 to 2.0 gy daily fractions . conventional or three - dimensional treatment planning using three- or four - field techniques was used . chemotherapy was administered concurrently with radiation therapy using a fluoropyrimidine - based regimen ( n=23 , 85% ) or irinotecan - based regimen ( n=4 , 15% ) . four to 8 weeks after completion of preoperative crt , le was performed by a transanal approach under general anesthesia . nineteen patients ( 70% ) received adjuvant chemotherapy comprising a fluoropyrimidine - based regimen ( n=18 , 67% ) or oxaliplatin - based regimen ( n=1 , 4% ) . the chemotherapeutic regimens , both preoperative and postoperative , were selected for each patient according to the preferences of the attending medical oncologists . all patients underwent a standard pretreatment workup including medical history , physical examination , serum carcinoembryonic antigen level , and imaging studies including chest x - ray and computed tomography ( ct ) , transrectal ultrasonography , f - fluorodeoxyglucose positron emission tomography , or magnetic resonance imaging . the response to preoperative crt was evaluated using the tumor regression grading system proposed by dworak et al . . tumor regression was graded as follows : grade 0 , no regression ; grade 1 , minimal regression ; grade 2 , moderate regression ; grade 3 , near - complete regression ; and grade 4 , complete regression . all tumors were staged according to the american joint committee on cancer staging manual 7th edition . all patients underwent standardized follow - up comprising a physical examination , digital rectal examination , complete blood counts , biochemical profiles , and serum carcinoembryonic antigen level at each visit . follow - up imaging studies , such as abdominopelvic ct and colonoscopy , were performed as clinically indicated or at the physician 's discretion . disease recurrence was pathologically proven by surgical resection , biopsy , or cytology and/or radiological findings . the primary endpoint was relapse - free survival ( rfs ) , defined as the time interval from the initiation of crt to any type of recurrence other than death . local failure was defined as any disease recurrence within the pelvis , and any failure outside the pelvis was classified as a distant metastasis . survival was estimated using the kaplan - meier method , with differences compared using the log - rank test . table 1 shows the individual and clinical characteristics of the patients . at the time of diagnosis , all patients had an eastern cooperative oncology group performance status of 0 to 1 . all tumors were assessed by digital rectal examination and were located within 7 cm of the anal verge . in the present study , the most common reasons for undergoing le were good clinical response and doctor 's recommendation ( n=14 , 52% ) and patient 's refusal of radical surgery ( n=8 , 30% ) , followed by old age ( n=2 , 7% ) , medical inoperability ( n=2 , 7% ) , and unknown ( n=1 , 4% ) . two patients were considered medically inoperable owing to poor pulmonary function and cerebrovascular accident , respectively . the duration of crt was 29 to 42 days ( median , 37 days ) . one patient did not complete the planned radiation therapy ( 45 gy ) at a dose of 39.6 gy due to severe enteritis . another patient received three of six cycles of postoperative capecitabine due to a cardiovascular event . the median follow - up time was 81.8 months ( range , 28.6 to 138.5 months ) . the 5-year local relapse - free survival ( lrfs ) , distant metastasis - free survival ( dmfs ) , rfs , and overall survival ( os ) were 88.9% , 81.1% , 77.8% , and 85.0% , respectively . six ( 22% ) patients developed treatment failure during the follow - up period : one ( 4% ) patient had local recurrence only ; three ( 11% ) patients had distant recurrence only ; and two ( 7% ) patients had both . among six patients with disease recurrence , three were alive at the last follow - up with a relapse - free status after salvage treatment : one patient ( ypt0n0 ) who developed local recurrence only at the excision site after 14 months was salvaged with abdominoperineal resection ( rpt2n0 ) and adjuvant chemotherapy ( six cycles of 5-fluorouracil plus leucovorin ) ; another patient with hepatic metastasis was salvaged with radiofrequency ablation and chemotherapy ; and the other patient with both local and distant recurrences was treated with salvage chemotherapy ( capecitabine plus oxaliplatin ) . during the study period until the time of analysis , a total of five ( 19% ) patients died : three ( 11% ) died of disease recurrence ; one ( 4% ) died of newly developed non - small - cell lung cancer ; and one ( 4% ) died of an unknown cause ( no known recurrence ) . in this study in one patient , recurrence did not occur during the follow - up period , and in the other two , it occurred only in a distant organ , thus our results indicated that margin positivity did not increase local recurrence . univariate analysis was performed to identify the prognostic value of all clinicopathologic factors listed in tables 1 and 2 . the 5-year os ( 94.1% vs. 66.7% , p=0.073 ) ( fig . 1b ) were better in patients with ypt0 - 1 than in those with ypt2 - 3 , respectively , with borderline significance . the 5-year lrfs rates for patients with ypt0 - 1 and ypt2 - 3 were 94.1% and 77.8% , respectively ( p=0.244 ) ( fig . the dmfs rate of patients with ypt0 - 1 was significantly better than that of ypt2 - 3 ( 94.1% vs. 55.6% , respectively ; p=0.016 ) ( fig . none of the other variables tested were significantly correlated with lrfs , dmfs , rfs , or os . table 1 shows the individual and clinical characteristics of the patients . at the time of diagnosis , all patients had an eastern cooperative oncology group performance status of 0 to 1 . all tumors were assessed by digital rectal examination and were located within 7 cm of the anal verge . in the present study , the most common reasons for undergoing le were good clinical response and doctor 's recommendation ( n=14 , 52% ) and patient 's refusal of radical surgery ( n=8 , 30% ) , followed by old age ( n=2 , 7% ) , medical inoperability ( n=2 , 7% ) , and unknown ( n=1 , 4% ) . two patients were considered medically inoperable owing to poor pulmonary function and cerebrovascular accident , respectively . the duration of crt was 29 to 42 days ( median , 37 days ) . one patient did not complete the planned radiation therapy ( 45 gy ) at a dose of 39.6 gy due to severe enteritis . another patient received three of six cycles of postoperative capecitabine due to a cardiovascular event . the median follow - up time was 81.8 months ( range , 28.6 to 138.5 months ) . the 5-year local relapse - free survival ( lrfs ) , distant metastasis - free survival ( dmfs ) , rfs , and overall survival ( os ) were 88.9% , 81.1% , 77.8% , and 85.0% , respectively . six ( 22% ) patients developed treatment failure during the follow - up period : one ( 4% ) patient had local recurrence only ; three ( 11% ) patients had distant recurrence only ; and two ( 7% ) patients had both . among six patients with disease recurrence , three were alive at the last follow - up with a relapse - free status after salvage treatment : one patient ( ypt0n0 ) who developed local recurrence only at the excision site after 14 months was salvaged with abdominoperineal resection ( rpt2n0 ) and adjuvant chemotherapy ( six cycles of 5-fluorouracil plus leucovorin ) ; another patient with hepatic metastasis was salvaged with radiofrequency ablation and chemotherapy ; and the other patient with both local and distant recurrences was treated with salvage chemotherapy ( capecitabine plus oxaliplatin ) . during the study period until the time of analysis , a total of five ( 19% ) patients died : three ( 11% ) died of disease recurrence ; one ( 4% ) died of newly developed non - small - cell lung cancer ; and one ( 4% ) died of an unknown cause ( no known recurrence ) . in this study , there were three patients who had resection margin positive . in one patient , recurrence did not occur during the follow - up period , and in the other two , it occurred only in a distant organ , thus our results indicated that margin positivity did not increase local recurrence . univariate analysis was performed to identify the prognostic value of all clinicopathologic factors listed in tables 1 and 2 . the 5-year os ( 94.1% vs. 66.7% , p=0.073 ) ( fig . 1b ) were better in patients with ypt0 - 1 than in those with ypt2 - 3 , respectively , with borderline significance . the 5-year lrfs rates for patients with ypt0 - 1 and ypt2 - 3 were 94.1% and 77.8% , respectively ( p=0.244 ) ( fig . the dmfs rate of patients with ypt0 - 1 was significantly better than that of ypt2 - 3 ( 94.1% vs. 55.6% , respectively ; p=0.016 ) ( fig . none of the other variables tested were significantly correlated with lrfs , dmfs , rfs , or os . the purpose of this study was to evaluate the treatment outcomes of patients with larc who underwent le following preoperative crt . at present , nevertheless , there has been increasing interest in the use of le as a fallback option for larc as well as early rectal cancer . some patients who want a better functional outcome and quality of life may refuse radical surgery mostly due to nonacceptance of permanent colostomy . however , one of the major problems related to le for larc is the higher recurrence rate . two cooperative group trials have provided information on the local recurrence rates of le followed by adjuvant crt for larc . the radiation therapy oncology group protocol 89 - 02 evaluated the efficacy of le in 38 patients with ct2 - 3 rectal cancer and reported that le was a feasible alternative treatment but that the local recurrence rates ( 16% in t2 and 23% in t3 ) and distant dissemination rates ( 12% in t2 and 31% in t3 ) appeared to escalate with increasing t classification . the cancer and leukemia group b ( calgb ) 8,984 study reported the updated outcomes of 51 patients with t2 rectal cancer . thus , the high rate of local recurrence with le remains unresolved , and the advantages of le should be balanced against this high local recurrence rate . several studies have shown promising results for le after preoperative crt in patients with select ct2 - 3 tumors that responded well to crt . preoperative crt allows downstaging of the primary tumor , sterilization of micrometastases in the pelvis , improved locoregional control , and decreased complication rates . among these , significant tumor responses to preoperative crt may lead to the use of le even in patients at a high risk of disease recurrence because a pathologically complete response ( ypcr ) after crt was suggested to have a favorable outcome . the key rationale for this approach is the correlation between radiosensitivity and the inherent low aggressiveness of rectal cancer . .   demonstrated that local control and survival rates of patients treated with crt followed by le were comparable to those of patients treated with crt followed by mesorectal excision . borschitz et al .   analyzed previously published data regarding le after preoperative crt for ct2 - 3 rectal cancer . the local recurrence rate of patients with ypt1 disease consistently showed a low incidence of 2% ( range , 0 to 6% ) , whereas those in patients with ypt2 and ypt3 were 6% to 20% and up to 42% , respectively . reported that selected patients with ct3 tumors that were downstaged and met the criteria for le appeared to have excellent survival outcomes . our study also showed that patients with ypt0 - 1 tumors had a trend toward better treatment outcomes than those with ypt2 - 3 tumors . the 5-year local recurrence and os rates in the present study for patients with ypt0 - 1 tumors were 5.9% and 94.1% , respectively , which were comparable to those reported for patients who underwent total mesorectal excision for early rectal cancer . we included 12 ( 44% ) patients with clinically positive pelvic lymph node(s ) who were diagnosed by one or more imaging studies . if lymph node metastasis can not be sterilized with preoperative crt , le in these patients may result in increased risks of local and distant recurrence because the residual lymphatic metastasis would have been left unresected . however , it is difficult to evaluate the status of lymph node involvement after preoperative crt because le did not provide information on ypn classification , and conventional imaging studies have limitations in assessing the response to preoperative crt for rectal cancer due to radiation - induced edema , inflammation , and fibrosis . kim et al .   reported that pathologic nodal classification is an important prognostic factor for survival outcomes in patients with rectal cancer treated with preoperative crt , and the ypt classification has been suggested as the most reliable predictor of ypn status : the ypn+ rate was 3.4% in ypt0 - 1 ; 16.9% in ypt2 ; and 49.3% in ypt3 patients . although the ypn classification was not reported in the present study , ypt classification may help to predict ypn status . we have confirmed an association between the tumor responses to preoperative crt and treatment outcomes . the results of the present study suggest that le may be a reasonable alternative treatment for patients with larc who achieve ypt0 - 1 after preoperative crt . although the treatment outcome of le in this patient subset seems promising , careful consideration should be given to preoperative patient selection . we hope that the results described here will add to the growing evidence and guide any future changes in the use of le for larc .