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      Long-term Oncological and Functional Outcomes of Chemoradiotherapy Followed by Organ-Sparing Transanal Endoscopic Microsurgery for Distal Rectal Cancer : The CARTS Study

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          Abstract

          Treatment of rectal cancer is shifting toward organ preservation aiming to reduce surgery-related morbidity. Short-term outcomes of organ-preserving strategies are promising, but long-term outcomes are scarce in the literature.

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          Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years.

          Rolf Sauer, Torsten Liersch, Susanne Merkel … (2012)
          Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months. A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival. Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival. There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.
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            The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma.

            Koen C M J Peeters, Corrie Marijnen, Iris Nagtegaal … (2007)
            To investigate the efficacy of preoperative short-term radiotherapy in patients with mobile rectal cancer undergoing total mesorectal excision (TME) surgery. Local recurrence is a major problem in rectal cancer treatment. Preoperative short-term radiotherapy has shown to improve local control and survival in combination with conventional surgery. The TME trial investigated the value of this regimen in combination with total mesorectal excision. Long-term results are reported after a median follow-up of 6 years. One thousand eight hundred and sixty-one patients with resectable rectal cancer were randomized between TME preceded by 5 x 5 Gy or TME alone. No chemotherapy was allowed. There was no age limit. Surgery, radiotherapy, and pathologic examination were standardized. Primary endpoint was local control. Median follow-up of surviving patients was 6.1 year. Five-year local recurrence risk of patients undergoing a macroscopically complete local resection was 5.6% in case of preoperative radiotherapy compared with 10.9% in patients undergoing TME alone (P < 0.001). Overall survival at 5 years was 64.2% and 63.5%, respectively (P = 0.902). Subgroup analyses showed significant effect of radiotherapy in reducing local recurrence risk for patients with nodal involvement, for patients with lesions between 5 and 10 cm from the anal verge, and for patients with uninvolved circumferential resection margins. With increasing follow-up, there is a persisting overall effect of preoperative short-term radiotherapy on local control in patients with clinically resectable rectal cancer. However, there is no effect on overall survival. Since survival is mainly determined by distant metastases, efforts should be directed towards preventing systemic disease.
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              High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study.

              Ane L Appelt, John Pløen, Henrik Harling … (2015)
              Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer.
              Article 0 comments Cited 143 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Title: JAMA Surgery
                Abbreviated Title: JAMA Surg
                Publisher: American Medical Association (AMA)
                ISSN (Print): 2168-6254
                Publication date (Electronic): October 10 2018
                Affiliations
                [1 ]Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
                [2 ]Department of Surgery, IJsselland Hospital, Capelle aan de Ijssel, the Netherlands
                [3 ]Department of Medical Oncology, Academic Medical Centre, Amsterdam, the Netherlands
                [4 ]Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
                [5 ]Department of Radiation Oncology, Erasmus Medical Centre, Rotterdam, the Netherlands
                [6 ]Department of Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, the Netherlands
                [7 ]Department of Surgery, Academic Medical Centre, Amsterdam, the Netherlands
                [8 ]Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
                [9 ]Department of Surgery, Amphia Hospital, Breda, the Netherlands
                [10 ]Department of Surgery, Medical Centre Slotervaart, Amsterdam, the Netherlands
                [11 ]Department of Surgery, Laurentius Hospital, Roermond, the Netherlands
                [12 ]Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands
                [13 ]Department of Surgery, Medical Centre Leeuwarden, Leeuwarden, the Netherlands
                [14 ]Department of Surgical Oncology, Erasmus Medical Centre, Rotterdam, the Netherlands
                [15 ]Department of Radiotherapy, Leiden University Medical Centre, Leiden, the Netherlands
                Article
                DOI: 10.1001/jamasurg.2018.3752
                PMC ID: 6439861
                PubMed ID: 30304338
                SO-VID: 87409791-031b-440c-aa43-eefc178131f3
                Copyright © © 2018
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