Indications and Outcome of Pelvic Exenteration for LocallyAdvanced Primary and Recurrent Rectal Cancer

Aneel Bhangu, MBChB, MRCS, S. Mohammed Ali, MBBS, MRCS, Gina Brown, MBBS, FRCR,R. John Nicholls, MChir, FRCS, and Paris Tekkis, MD, FRCS

Annals of SurgeryFebruary 2014

ObjectiveCompare the outcome of pelvis exenteration in patients with LAP and RRC in a high volume tertiary referral center Identify risks and benefits of pelvic exenteration for advanced rectal cancer in a multidisciplinary environment

Background1.23 new cases of RC in 200840,000 new cases in USA 14,000 in UK: 33% locally advanced (T4)Total mesorectal excision with neoadjuvant radiotherapy: margin negative rates of 90% and local recurrence rates between 6-10%6% will breach the mesorectal planeResectable RRC R0 rates: 37-57%Multivisceral exenterative surgical resection offers the best chance of cure for LAP and RRC

MethodsProspectively maintained database of Royal Marsden HospitalPatients undergoing surgery for LAP and RRC from Jan 2006 to Dec 2011Noncolorectal and benign retrorectal tumors were excludedPerformed by a colorectal team and supported by surgical oncology, spinal orthopedics, urology, gynecology and plastic surgery

Staging and Neoadjuvant TherapyClinical examination, endoscopy, MRI, CT scan and PET scanOrgan specific resection: likelihood of involvement, need for surgical access, risks and patient discussionRadiotherapy naive patients were offered a long-course chemoradiotherapy, others were given a booster Patients with multifocal disease, distant metastases were treated medicallySome patients proceeded directly to surgery if anatomically identified R0 resection planes on MRIRestaging was done after 6-8 weeks and surgery after 6 weeks of last radiological staging test

EndpointsPrimary: 3 year disease free survivalSeconday: 3 year overall survival, 3 year local recurrence free survival, resection margins and perioperative adverse effects

DefenitionsRRC: Locally recurrent, new sites of tumor in pelvis after previous surgeryLAP: Needing resection beyond mesorectum to achieve R0 (MRI)Margins: R0 -ve within 1mm, R1 +ve within 1mm, R2 invading marginAdverse: Intraoperative, major within 30 days, minor within 30 days, long term beyond 3 monthsDFS: Date of surgery to pelvic recurrence, distant disease or deathOS: Date of surgery to deathLRFS: Date of surgery to pelvic recurrence or death

Results272 rectal cancer resections: 172 for nonadvanced and 100 pelvic exenterations (55 LAP and 45 RRC)Median age 60, 70% men45 RRC patients: 32 anterior resections, 5 abdominoperineal resections, 3 exenterations, 2 local excisions and 1 Hartman. 33% took radiotherapyNeoadjuvant therapy: 70 chemoradiotherapy, 5 radiotherapy, omitted in 22% of LAP (12/55) and 29% of RRC (13/45)

SurgeryMost patients (49%) required resection of 2 compartments, 1 required resection of 4Anterior compartment: 65% (36/55) in LAP and 33% (15/45) in RRCPosterior compartment: 15% (8/55) in LAP and 53% (24/45) in RRCSacrectomy: 49% in RRC and 15% in LAP, 70% were for RRCInferior compartment: 27 patients, 19 required extralevator abdominoperineal resection ( 14 LAP and 5 RRC) with en bloc removal of coccyxCystectomy: 40% (22/55) in LAP and 31% (14/45) in RRCBowel reanastamosis: 32%Perineal reconstruction: 55%, 96% (53/55) flapAssociated procedures: 4 in LAP (3 syn hepatectomies, 1 syn para-aortic lymphadenectomy) 3 in RRC (1 staged hepatectomy, 1 syn RF ablation, 1 staged lung lobectomy)

Short Term OutcomeNo 30 day or inhospital mortalityMean blood loss 2048 ml: 1689 LAP 2444 RRC P=0.135Median duration of surgery 8.4 hrs, median stay in hospital 21 days (similar)Sacrectomy: longer duration, longer stay, higher blood lossCystectomy: longer durationPerineal flap: longer mean operating time and mean length of stay

Resection Margin and Pathological OutcomeR0 78%, R1 15%, R2 7%R0: 91% (50/55) in LAP, 62% (28/45) in RRCR1: 5% in LAP, 27% in RRCR2: 4% in LAP, 11% in RRCMost of +ve margin were on pelvic sidewall (10)Pathological complete response: 3 in LAP, 4 in RRC

Organ Specific ExenterationBased on preoperative MRI: 63.9% of cystectomies, 73.9% of prostatectomies, and all sacrectomiesTumor regression by histology: 30% of cystectomies, 41% of prostatectomies and 26% of sacrectomies

Adverse Events53% suffered at least one event: 49% in LAP and 58% in RRC98 separate events: 10 intraoperative, 28 30-day major, 38 30-day minor and 21 long termIntraoperative: 7 bleeding more than 5L,1 bleeding more than 17L, 1 ventricular fibrillation and 1 sciatic nerve injury

Disease Free SurvivalR0 67%, R1 49%, R2 0%70% for LAP and 50% for RRCR0: 76% for LAP and 57% for RRCPositive margin status and positive node staging were significant predictors for reduced DFS on multivariate Cox regression analysis

Overall SurvivalR0 82%, R1 55%, R2 0%78% in LAP 65% in RRCR0: 85% in LAP vs 79% in RRCPositive margin status and positive node staging were significant predictors of reduced OS

Local Recurrence Free SurvivalR0 85%, R1 46%84% in LAP and 72% in RRCR0: 86% in LAP and 84% in RRCOnly positive margin status was a significant predictor of a reduced LRFS

ConclusionThe key prognostic indicator for outcome from pelvis exenteration for LAP and RRC is resection margin statusMore important than wether the tumor is primary or recurrentPatients with RRC are at a higher risk for positive marginsLong term survival for both LAP and RRC can be achieved with pelvic exenteration although morbidity could be highSurvival after R0 resection is excellent and exenteration should be offered where resection beyond TME planes is requiredThorough preoperative planning and high quality surgery are required to maximize the chances of R0 resection