title: Individualizing surgical treatment based on tumour response following neoadjuvant therapy in T4 primary rectal cancer.
abstract: BACKGROUND
  Rectal cancer involving at least one adjacent organ (mrT4b) requires multi-visceral resection to achieve clear resection margin (R0). Performing pelvic compartment preservation according to the tumour response has not been considered. This study assesses the impact of changing the surgical strategy according to tumour response in rectal cancer mrT4b.
  
  
  METHODS
  Patients with non-metastatic T4b rectal cancer at two tertiary referral centres between 2008 and 2013 were grouped as "Responders" ypT0-3abNx versus "Non-responders" ypT3cd-4Nx and divided into three surgical procedures: total mesorectal excision (TME), extended-TME (eTME) and beyond-TME (b-TME). End-points were circumferential resection margin, postoperative morbidity, definitive stoma formation, 3-years local recurrence (3y-LR) and 3-years disease-free survival (3y-DFS) according to both tumours' response and surgical procedures.
  
  
  RESULTS
  Among 883 patients with rectal cancer, 101 were included. Responders had a higher rate of induction chemotherapy (59.7% vs. 38.2%; p = 0.04). Morbidity and definitive stoma formation were significantly higher in Non-responders. R0 was not impacted by either the tumour response or the surgical procedures. The 3y-LR was lower in Responders (14%) compared to Non Responders (32%) (HR 1.6; 95% CI: 1.02-2.59; p = 0.041), and was two-fold higher in e-TME compared to b-TME in Non-responders, whereas no difference was found in Responders. The 3y-DFS was higher in Responders irrespective to the surgery (71% vs. 47%; p = 0.07).
  
  
  CONCLUSIONS
  In Responders, TME or e-TME are technically and oncollogically feasible and should be considered in preferrence to b-TME. In Non-responders, allowing for high rates of morbidity and local recurrence in patients with e-TME, b-TME procedures should be preferred.
authors.affiliation: CHU of Bordeaux, Department of Surgery, Saint-Andre Hospital, University of Bordeaux, Bordeaux, France. Electronic address: quentin.denost@chu-bordeaux.fr.
authors.forename: Q
authors.initials: Q
authors.lastname: Denost
authors.affiliation: Department of Colorectal Surgery, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK; Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK.
authors.forename: C
authors.initials: C
authors.lastname: Kontovounisios
authors.affiliation: Department of Colorectal Surgery, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK; Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rasheed
authors.affiliation: CHU of Bordeaux, Department of Surgery, Saint-Andre Hospital, University of Bordeaux, Bordeaux, France.
authors.forename: R
authors.initials: R
authors.lastname: Chevalier
authors.affiliation: Department of Colorectal Surgery, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Brasio
authors.affiliation: CHU of Bordeaux, Department of Surgery, Saint-Andre Hospital, University of Bordeaux, Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Capdepont
authors.affiliation: CHU of Bordeaux, Department of Surgery, Saint-Andre Hospital, University of Bordeaux, Bordeaux, France.
authors.forename: E
authors.initials: E
authors.lastname: Rullier
authors.affiliation: Department of Colorectal Surgery, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK; Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK.
authors.forename: P P
authors.initials: PP
authors.lastname: Tekkis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy; D005260:Female; D005602:France; D006801:Humans; D008131:London; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D057285:Precision Medicine; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Beyond-total mesorectal excision; Locally advanced rectal cancer; Pelvic exenteration; Rectal cancer; T4 cancer; Total mesorectal excision