Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: a longitudinal prospective study. A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer. Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery. Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC).
To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer.
                We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses.
                Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas.
                One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised. A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.
                This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.
                Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.
                Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.
                This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased. The aim of this study was to compare the downstaging achieved after long-course chemoradiotherapy (chRT) and short-term radiotherapy (sRT) followed by delayed surgery.
                A randomized controlled trial was carried out. Eighty-three patients with resectable stage II and III rectal adenocarcinoma were randomized to receive long-course chemoradiotherapy (46) and short-term radiotherapy (5×5 Gy) (37). Surgery was performed 6 weeks after preoperative treatment in both groups.
                The R0 resection rate was 91.3% in the chRT and 86.5% in the sRT group (P=0.734). Sphincter preservation rates were 69.6%vs 70.3% (P=0.342) and postoperative complication rates were 26.1%vs 40.5% (P=0.221). There were more patients with early pT stage [pT0 (complete pathological response) pT1] in the chRT group [21.8%vs 2.7% (P=0.03)] and more patients with pT3 disease in the sRT group [75.7%vs 52.2% (P=0.036)]. There were no differences in pN stage and lymphatic or vascular invasion in either group. Pathological downstaging (stage 0 and I) was observed in eight (21.6%) patients in the sRT group and in 18 (39.1%) in the chRT group (P=0.07). Tumours were smaller after preoperative ChRT (2.5 cm vs 3.3 cm; P=0.04).
                Long-course preoperative chemoradiation resulted in greater statistically significant tumour downsizing and downstaging compared with short-term radiation, but there was no difference in the R0 resection rates. Similar postoperative morbidity was observed in each group.
                © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland. A population based prospective randomized trial on preoperative radiotherapy in operable rectal cancer was conducted in Stockholm, Sweden. Five hundred fifty-seven patients from 12 institutions were included with histologically proven, clinically resectable rectal adenocarcinoma. Patients planned for local excision or previously irradiated to the pelvis were excluded.
                A total of 272 patients were allocated to preoperative irradiation with 25 Gy in five cycles during 5-7 days to the rectum and the pararectal tissues (RT+ group) and 285 patients were allocated to surgery only (RT- group). The median follow-up time was 50 months. No patient was lost to follow-up. Surgery was considered curative in 479 patients (86%).
                Locoregional recurrence occurred in 10% of the patients in the RT+ group versus 21% in the RT- group (p < 0.01). Among the curatively operated patients, distant metastases occurred in 19% in the RT+ group versus 26% in the RT- group (p = 0.02). The overall survival was improved in the irradiated patients (p = 0.02). Postoperative complications were more common after irradiation but were usually mild. The postoperative mortality was low in both groups.
                Preoperative short-term, high-dose radiotherapy as given in this trial reduces the risk of local and distant recurrence and improves survival after curative surgery for rectal carcinoma. In the latter 1990s, adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan. We conducted two independent randomized controlled trials in patients with Stage III colon and rectal cancer.
                Patients were randomly assigned to receive surgery alone or surgery followed by treatment with UFT (400 mg/m²/day), given for five consecutive days per week for 1 year. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS).
                A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. The patients' characteristics were similar between the UFT group and the Surgery-alone group. There was no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the Surgery-alone group. The only grade 4 toxicity in the UFT group was diarrhea, occurring in one patient with colon cancer and one patient with rectal cancer.
                Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.89).
Compared to preoperative RT alone, preoperative CRT enhances pathological response and improves local control in resectable stage II and III rectal cancer, but does not benefit disease free or overall survival. The effects of preoperative CRT on functional outcome and quality of life are incompletely understood and should be addressed in future trials.