A. Rutkowski

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: A prospective multicentre study

PURPOSE To assess local control after preoperative radiation and local excision and to determine an optimal radiotherapy regimen. METHODS Eighty-nine patients with G1-2 rectal adenocarcinoma <3-4 cm; unfavourable cT1N0 (23.6%), cT2N0 (62.9%) or borderline cT2/cT3N0 (13.5%) received 5 × 5 Gy plus 4 Gy boost (71.9%) or 55.8 Gy in 31 fractions with 5-FU and leucovorin (28.1%). Local excision (traditional technique 56.2%, transanal endoscopic microsurgery 41.6%, Kraske procedure 2.2%) was performed 6-8 weeks later. If patients were downstaged to ypT0-1 without unfavourable factors (good responders), this was deemed definitive treatment. Immediate conversion to radical surgery was recommended for remaining patients. RESULTS Good response to radiation was seen in 67.2% of patients in the short-course group and in 80.0% in the chemoradiation group, p = 0.30. Local recurrence at 2 years (median follow-up) in good responders was 11.8% in the short-course group and 6.2% in the chemoradiation group, p = 0.53. In the total group, a lower rate of local recurrence at 2 years was observed in elderly patients (>69 years, median value) when compared to the younger patients; 8.3% vs. 27.7%, Cox analysis hazard ratio 0.232, p = 0.016. A total of 18 patients initially managed with local excision required conversion to abdominal surgery but either refused it or were unfit. In this group, local recurrence at 2 years was 37.1%. CONCLUSIONS This study suggests an acceptable local recurrence rate after preoperative radiotherapy and local excision of small, radiosensitive tumours in elderly patients.

Is the 1-cm Rule of Distal Bowel Resection Margin in Rectal Cancer Based on Clinical Evidence? A Systematic Review

Background Distal intramural spread is present within 1 cm from visible tumor in a substantial proportion of patients. Therefore, ≥1 cm of distal bowel clearance is recommended as minimally acceptable. However, clinical results are contradictory in answering the question of whether this rule is valid. The aim of this review was to evaluate whether in patients undergoing anterior resection, a distal bowel gross margin of <1 cm jeopardizes oncologic safety.

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study

BACKGROUND Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER The trial is registered as ClinicalTrials.gov number NCT00833131.

Neoadjuvant treatment for unresectable rectal cancer: an interim analysis of a multicentre randomized study.

PURPOSE To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer. METHODS Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment. RESULTS 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II. CONCLUSIONS The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies.

Palliative radiotherapy and chemotherapy instead of surgery in symptomatic rectal cancer with synchronous unresectable metastases: a phase II study.

BACKGROUND In stage IV rectal cancer, palliative surgery is often carried out upfront. This study investigated whether the surgery can be avoided. PATIENTS AND METHODS Forty patients with symptomatic primary rectal adenocarcinoma and synchronous distant metastases deemed to be unresectable received 5 × 5 Gy irradiation and then oxaliplatin-based chemotherapy. Before treatment, 38% of patients had a near-obstructing lesion. The palliative effect was evaluated by questionnaires completed by the patients. RESULTS The median follow-up for living patients was 26 months (range 19-34). The median overall survival was 11.5 months. Eight patients (20%) required surgery during the course of their disease: seven patients required stoma creation and one had local excision. Thirty percent of patients had a complete resolution of pelvic symptoms during the whole course of the disease, and 35% had significant improvement. In the subgroup with a near-obstructing lesion, 23% of patients required stoma creation. In all patients, the probability of requiring palliative surgery at 2 years was 17.5% [95% confidence interval (CI) 13% to 22%), and the probability of sustained good palliative effect after radiotherapy and chemotherapy was 67% (95% CI 58% to 76%). CONCLUSION Short-course radiotherapy and chemotherapy allowed most patients to avoid surgery, even those with a near-obstructing lesion. CLINICALTRIALS The trial is registered with ClinicalTrials.gov: number NCT01157806.

Anorectal and sexual functions after preoperative radiotherapy and full-thickness local excision of rectal cancer.

AIMS Local excision with preoperative radiotherapy may be considered as alternative management to abdominal surgery alone for small cT2-3N0 tumours. However, little is known about anorectal and sexual functions after local excision with preoperative radiotherapy. Evaluation of this issue was a secondary aim of our previously published prospective multicentre study. METHODS Functional evaluation was based on a questionnaire completed by 44 of 64 eligible disease-free patients treated with preoperative radiotherapy and local excision. Additionally, ex post, these results were confronted with those recorded retrospectively in the control group treated with anterior resection alone (N = 38). RESULTS In the preoperative radiotherapy and local excision group, the median number of bowel movements was two per day, incontinence of flatus occurred in 51% of patients, incontinence of loose stool in 46%, clustering of stools in 59%, and urgency in 49%; these symptoms occurred often or very often in 11%-21% of patients. Thirty-eight per cent of patients claimed that their quality of life was affected by anorectal dysfunction. Nineteen per cent of men and 20% of women claimed that the treatment negatively influenced their sexual life. The anorectal functions in the preoperative radiotherapy and local excision group were not much different from that observed in the anterior resection alone group. CONCLUSIONS Our study suggests that anorectal functions after preoperative radiotherapy and local excision may be worse than expected and not much different from that recorded after anterior resection alone. It is possible that radiotherapy compromises the functional effects achieved by local excision.

Watch and wait policy after preoperative radiotherapy for rectal cancer; management of residual lesions that appear clinically benign

BACKGROUND During an ongoing phase II observational study on watch and wait policy in rectal cancer, a substantial number of patients presented residual lesion after radiotherapy with a clinical benign appearance. This article aims to discuss the clinical significance of such findings. MATERIALS AND METHODS Main entry criteria were age ≥70 years and small tumour (≤5 cm and ≤60% of circumferential involvement) located in the low rectum. Patients received chemoradiation (50 Gy, 2 Gy per fraction concomitantly with a 5-Fu bolus and leucovorin) or 5 × 5 Gy if considered unfit for chemotherapy. Patients with clinical complete response (cCR) were observed. Those with persistent tumours underwent transanal endoscopic microsurgery [TEM] if the baseline tumour was ≤3 cm and cN0 or total mesorectal excision. RESULTS The watch and wait procedure was used in 11 out of the total 35 patients (31%) with a cCR; 17 patients (49%) with residual tumours that appeared clinically malignant were referred for TEM or abdominal surgery. In the remaining seven (20%), the residual tumour clinically appeared benign. Of these, there were two invasive cancers, four high-grade dysplasias and one low-grade dysplasia. The five patients with dysplasia, underwent local lesion resection without recurrence within a median of 11 months follow-up. CONCLUSIONS The majority of lesions that appeared clinically benign after radio(chemo)therapy were also benign on pathological examination. Thus, local excision of such lesions should be considered.

Risk of permanent stoma after resection of rectal cancer depending on the distance between the tumour lower edge and anal verge.

The distance between the anal verge and lower edge of rectal cancer is one of the most important factors affecting the feasibility of sphincter-preserving resection.The aim of the study was to assess the risk of permanent stoma after resection of rectal tumour depending on the distance between the tumour and the anal verge.Material and methods. The retrospective analysis covered 884 patients after resection of rectal cancer. The distance between the anal verge and the lowest edge of the tumour was measured during endoscopic examination. Surgical technique was similar in all cases. For statistical analysis, the chi-square test and Fisher exact test were used.Results. The overall rate of sphincter-preserving procedures was 71.8%, 90.1% of which were anterior resections. The greatest differences between the rate of anterior resections were noted for the segment between the 4th and the 5th centimetres: 30.1% for 4 cm vs 66.7% for 5 cm, p = 0.005. Overall, in 328 patients (37.1%) surgical treatment resulted in a permanent stoma. The number included: 246 (75.0%) patients after abdominosacral resection, 44 (13.4%) patients after the Hartmann procedure, three (0.9%) patients after proctocolectomy, and 28 (8.5%) patients after anterior resection, with a permanent stoma as a result of anastomotic leak. The overall rate of anastomotic leak was 11.7%. Formation of a defunctioning stoma in patients with a low-lying (6 cm from the anal verge) tumour reduced the risk of symptomatic anastomotic leak: 6.3% vs 20.5%; p = 0.049.Conclusions. Anterior resection of tumours located 6 cm from the anal verge is feasible in 90%. Anastomotic leak that requires reoperation increases the risk of permanent colostomy. In selected cases, formation of a defunctioning stoma after resection of low-lying rectal cancer can reduce the risk of permanent colostomy.

Extralevator abdomino-perineal excision (ELAPE) or abdomino-sacral amputation of the rectum (ASAR): revitalized approach for low rectal carcinoma described by Tadeusz Koszarowski in the 50s.

In the November issue of the Journal Ramsay et al. reported their outcomes from a single centre using the socalled levator sparing dissection and concluded that (with adequate neoadjuvant chemoradiotherapy), this technique of the excision of rectum remains a safe option (positive circumferential resection margin in 7 out of 43 patients operated with curative intent) with less morbidity and perioperative complications than has been described for extralevator abdomino-perineal excision (ELAPE). The authors stated that the ELAPE technique was originally described by Miles and later popularized by Holm, who also addressed reconstruction of perineal defect with a gluteus maximus flap. The anatomically based terminology of ELAPE has been applied regardless of the patient’s position, although the prone position is believed to facilitate vision, access and teaching, as well as bleeding control ease. In efforts to provide precision terminology for precision surgery, the term of abdomino-sacral amputation of the rectum (ASAR) has been neglected. The principle of operation is the perineal/sacral dissection done in the prone position and the levator muscles are resected en bloc with the anus and lower rectum. To our best knowledge the first operation using this technique was performed in Poland by professor Tadeusz Koszarowski at the Maria Sklodowska-Curie Memorial Cancer Centre in Warsaw, on December 7th, 1949. The description of ASAR in the prone position, after completion of the abdominal phase of the procedure in the supine position and turning of the patient, underlines the principle of the cylindrical specimen’s shape, achieved by a wide excision of the levator complex in order to reduce the involvement of the circumferential margin by tumour (Fig. 1). Early and late results of the first case series treated with ASAR were published in 1956. In the group of 35 patients in the mean age of 51.6 years, postoperative