Increased risk for second primary rectal cancer after pelvic radiation therapy.

BACKGROUND: The aim of this study was to analyse the association between pelvic radiation therapy (RT) and the development of rectal cancer as a second primary cancer. METHODS: Data on patients treated for a primary pelvic cancer between 1989 and 2007 were retrieved from the population-based Netherlands Cancer Registry. Patients treated for more than one pelvic cancer were excluded. To estimate the cumulative incidence of rectal cancer, Fine and Gray's competing risk model was used with death as a competing event. Survival was calculated using multivariable Cox regression. RESULTS: A total of 192,658 patients were included, of which 62,630 patients were treated with RT for their pelvic cancer. Primary tumours were located in the prostate (50.1%), bladder (19.2%), endometrium (13.9%), ovaries (10.0%), cervix (6.4%) and vagina (0.4%). At a median interval of 6 years (range 0-24), 1369 patients developed a rectal cancer. Overall, the risk for rectal cancer was increased in patients who underwent RT for the previous pelvic cancer (subhazard ratio [SHR]: 1.72, 95% confidence interval [CI]: 1.55-1.91). Analysis for each tumour location specifically showed an increased risk in patients who received RT for prostate (SHR: 1.89, 95% CI: 1.66-2.16) or endometrial cancer (SHR: 1.50, 95% CI: 1.13-2.00). A protective effect of RT was observed for patients with bladder cancer (SHR 0.67, 95% CI: 0.47-0.94). There was no survival difference between patients with rectal cancer with or without previous RT (hazard ratio: 0.94, 95% CI: 0.79-1.11). CONCLUSIONS: Patients who received RT for a previous pelvic cancer were at increased risk for rectal cancer. The risk was modest and pronounced in patients receiving RT for prostate and endometrial cancer.

Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo) Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study.

INTRODUCTION: Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery. METHODS AND ANALYSIS: STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2. ETHICS AND DISSEMINATION: The medical ethical committees of all the participating countries have approved the study protocol. Results of the primary and secondary endpoints will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN14240288, 20 October 2016. NCT02945566; Pre-results, October 2016.

Treatment of Locally Recurrent Rectal Carcinoma in Previously (Chemo)Irradiated Patients: A Review.

BACKGROUND: Local recurrence after rectal cancer treatment occurs in ≈5% to 10% of patients. Neoadjuvant (chemo)radiotherapy for primary rectal cancer renders treatment of recurrent disease more difficult. OBJECTIVE: The purpose of this study was to review contemporary multimodality therapies, including their outcome, for locally recurrent rectal carcinoma after (chemo)radiotherapy and complete surgical resection of primary rectal cancer. DATA SOURCES: A comprehensive literature search of PubMed and EMBASE was performed. STUDY SELECTION: All English language articles presenting original patient data regarding treatment and the respective outcome of previously irradiated locally recurrent rectal cancer were included. INTERVENTIONS: All of the treatment modalities for locally recurrent rectal cancer were reviewed. MAIN OUTCOME MEASURES: Primary outcome parameters were local control, metastasis-free survival, and overall survival. Secondary outcome parameters were perioperative morbidity and mortality, and prognostic factors for treatment outcome. RESULTS: Of 854 studies, 9 studies and 474 patients with locally recurrent rectal carcinoma were included. Various treatment regimens were used, most with curative intent. Reirradiation was composed of (neo-)adjuvant external beam radiotherapy (with or without concurrent chemotherapy), additional intraoperative radiotherapy, or intraoperative radiotherapy only. Surgical technique highly varied, depending on the extent of the lesion. Radiation toxicity, perioperative morbidity, and mortality were generally acceptable. Outcome was better after curative intent treatment, any surgical resection, and R0 resections in particular. Moreover, reirradiation is associated with increased complete resection rates, which in turn positively affected local control and overall survival. LIMITATIONS: Most studies were retrospectively designed, with highly variable therapies, patient populations, and duration of follow-up. CONCLUSIONS: A complete resection is the most important prognostic factor and should be the goal of treatment in locally recurrent rectal carcinoma. Reirradiation seems safe and of additional value in reaching a complete resection. Considering the available evidence, at present reirradiation should be given on a case-specific basis, with all of the patients entering an international prospective database.

Does radiotherapy of the primary rectal cancer affect prognosis after pelvic exenteration for recurrent rectal cancer?

BACKGROUND: Radiotherapy reduces local recurrence rates but is also capable of short- and long-term toxicity. It may also render treatment of local recurrence more challenging if it develops despite previous radiotherapy. OBJECTIVE: This study examined the impact of radiotherapy for the primary rectal cancer on outcomes after pelvic exenteration for local recurrence. DESIGN: We conducted a retrospective review of exenteration databases. SETTING: The study took place at a quaternary referral center that specializes in pelvic exenteration. PATIENTS: Patients referred for pelvic exenteration from October 1994 to November 2012 were reviewed. Patients who did and did not receive radiotherapy as part of their primary rectal cancer treatment were compared. MAIN OUTCOME MEASURES: The main outcomes of interest were resection margins, overall survival, disease-free survival, and surgical morbidities. RESULTS: There were 108 patients, of which 87 were eligible for analysis. Patients who received radiotherapy for their primary rectal cancer (n = 41) required more radical exenterations (68% vs 44%; p = 0.020), had lower rates of clear resection margins (63% vs 87%; p = 0.010), had increased rates of surgical complications per patient (p = 0.014), and had a lower disease-free survival (p = 0.022). Overall survival and disease-free survival in patients with clear margins were also lower in the primary irradiated patients (p = 0.049 and p < 0.0001). This difference in survival persisted in multivariate analysis that corrected for T and N stages of the primary tumor. LIMITATIONS: This study is limited by its retrospective nature and heterogeneous radiotherapy regimes among radiotherapy patients. CONCLUSIONS: Patients who previously received radiotherapy for primary rectal cancer treatment have worse oncologic outcomes than those who had not received radiotherapy after pelvic exenteration for locally recurrent rectal cancer.