The treatment of early rectal cancer in the era of adjuvant and neo-adjuvant therapy

Abstract

The accurate staging of rectal cancer improves the stratification of patients for adjuvant therapy. Staging of tumor with endoluminal ultrasonography (EUS) shows a good correlation with histology (κ = 0.85; 95% confidence interval 0.76-0.95). Overall pT and pN stage accuracy of EUS was 92% and 65% respectively. The staging of local disease can be further augmented by EUS guided fine needle aspiration of extra rectal lesions lying within or outside of the mesorectum. In a systematic review of local excision after neoadjuvant therapy a total of 22 unique studies reporting on 1068 patients were analysed. At a median follow-up of 54 months, ypT0 tumours had a pooled local recurrence rate of 4% and a median disease-free survival rate of 95%. Outcomes for ≥ ypT1 tumours were much worse with pooled local recurrence and disease-free survival of 22% and 68%, respectively. In a review of 22 studies, 804 patients who underwent local excision followed by adjuvant therapy either for unfavourable histology, prohibitive comorbidity or patient choice. the pooled local recurrence was 5.8% for pT1 tumours, 13.8% for pT2 tumours and 33.7% for pT3 tumours. In addition, the response to radiotherapy may be enhanced by aspirin, metformin and statins.

Keywords

Early rectal cancer / local excision / neoadjuvant chemoradiotherapy

References

[1] Aitken RJ.Mesorectal excision for rectal cancer.Br J Surg1996;83:214-6

[2] Enker WE,Cranor ML.Total mesorectal excision in the operative treatment of carcinoma of the rectum.J Am Coll Surg1995;181:335-46

[3] van Gijn W,Nagtegaal ID,Putter H,Rutten HJ,Glimelius B.Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow up of the multicentre, randomised controlled TME trial.Lancet Oncol2011;12:575-82

[4] Pettersson D,Holm T,Påhlman L,Martling A.Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer.Br J Surg2010;97:580-7

[5] National Collaborating Centre for Cancer. Colorectal Cancer: The Diagnosis and management of Colorectal Cancer. Cardiff, United Kingdom: National Collaborating Centre for Cancer; 2011

[6] Penninckx F,Van de Stadt J,Mansvelt B,Van Eycken E,Fieuws S.Outcome following laparoscopic and open total mesorectal excision for rectal cancer.Br J Surg2013;100:1368-75

[7] van der Pas MH,Cuesta MA,Lacy AM,Bonjer HJ.Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial.Lancet Oncol2013;14:210-8

[8] Fleshman J,Sargent DJ,George V,Peters WRJr,Chang G,Fichera A,Wexner S,Marks J,Margolin D,Marcello P,Read T,Wren SM,Nelson H.Effect of laparoscopic assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial.JAMA2015;314:1346-55 PMCID:PMC5140087

[9] Hendren SK,Liu M,Cohen Z,Macrae HM,McLeod RS.Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer.Ann Surg2005;242:212-23 PMCID:PMC1357727

[10] Engel J,Schlesinger-Raab A,Sauer H.Quality of life in rectal cancer patients: a four-year prospective study.Ann Surg2003;238:203-13 PMCID:PMC1422675

[11] Wilson TR.Clinical and non-clinical factors influencing postoperative health-related quality of life in patients with colorectal cancer.Br J Surg2008;95:1408-15

[12] Wallner C,Bonsing BA,Wallace CN,Rutten HJ,Deruiter MC.Causes of fecal and urinary incontinence after total mesorectal excision for rectal cancer based on cadaveric surgery: a study from the Cooperative Clinical Investigators of the Dutch Total Mesorectal Excision Trial..J Clin Oncol2008;26:4466-72

[13] Maas M,Valentini V,Rödel C,Calvo FA,Glynne-Jones R,Mohiuddin M,Small WJr,Theodoropoulos G,Beets-Tan RG.Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data.Lancet Oncol2010;11:835-44

[14] de Campos-Lobato LF,da Luz Moreira A,Dietz DW,Fazio VW.Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence.Ann Surg Oncol2011;18:1590-8

[15] Garcia-Aguilar J,Avila K,Chu P.Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial..Ann Surg2011;254:97-102 PMCID:PMC3115473

[16] Hiotis SP,Cohen AM,Paty PB,Wagman R,Wong WD.Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients.J Am Coll Surg2002;194:131-5

[17] Chua YJ.Pathological complete response: still a relevant endpoint in rectal cancer?.Lancet Oncol2010;11:807-8

[18] Habr-Gama A,Proscurshim I.Complete clinical response after neoadjuvant chemoradiation for distal rectal cancer.Surg Oncol Clin N Am2010;19:829-45

[19] Bach SP,Monson JR,Lane L,Warren B.Transanal endoscopic microsurgery (TEM) Collaboration. a predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer..Br J Surg2009;96:280-90

[20] Hallam S,Thomas M.A systematic review of local excision after neoadjuvant therapy for rectal cancer: are ypT0 tumors the limit?.Dis Colon Rectum2016;59:984-97

[21] Norton SA.Staging of rectosigmoid neoplasia with colonoscopic endoluminal ultrasonography.Br J Surgery1999;86:942-6

[22] Glancey D,Thomas M.The role of colonoscopic endoanal ultrasound scanning (EUS) in selecting patients suitable for resection by transanal endoscopic microsurgery (TEM).Colorectal Dis2005;7:148-50

[23] Lim J,Wong NA.Endoscopic ultrasound guided fine needle aspiration of extra-rectal lesions.Tech Coloproctol2017;21:393-5

[24] Cuttin J,Thomas M.A systematic review of local excision followed by adjuvant therapy in early rectal cancer: are pT1 tumours the limit?.Colorectal Dis2018; accepted for publication:

[25] Swedish Rectal Cancer Trial; Cedermark B,Glimelius B,Rutqvist LE.Improved survival with preoperative radiotherapy in resectable rectal cancer..N Engl J Med1997;336:980-7

[26] Kapiteijn E,Nagtegaal ID,Steup WH,Rutten HJ,Glimelius B,Leer JW.Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer..N Engl J Med2001;345:638-46

[27] Sauer R,Hohenberger W,Wittekind C,Martus P,Hager E,Karstens J,Schmidberger H.Preoperative versus postoperative chemoradiotherapy for rectal cancer.N Engl J Med2004;351:1731-40

[28] Gash K,Cotton D,Thomas MG.Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy.Br J Cancer2017;117:210-9 PMCID:PMC5520519

[29] Restivo A,Casula G,Cabras F,Zorcolo L.Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer.Br J Cancer2015;113:1133-9 PMCID:PMC4647877

[30] Rothwell PM,Elwin C,Algra A,Meade TW.Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials.Lancet2010;376:1741-50

[31] Gash K,Chambers A,Williams A.Aspirin enhances the response to radiation in colorectal cancer cell lines.Gut2015;64 Suppl 1:A533

[32] Mace AG,Stocchi L.American Joint Committee on Cancer and College of American Pathologists regression grade: a new prognostic factor in rectal cancer.Dis Colon Rectum2015;58:32-44

[33] Rödel C,Papadoupolos T,Klimpfinger M,Liersch T,Raab R,Wittekind C.Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.J Clin Oncol2005;23:8688-96

[34] Roh MS,O'Connell MJ,Deutsch M,Kahlenberg MS,Ursiny CS,Wolmark N.Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03.J Clin Oncol2009;27:5124-30 PMCID:PMC2773471

[35] Habr-Gama A,Gama-Rodrigues J,Proscurshim I,Nadalin W.Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management?.Dis Colon Rectum2013;56:1109-17

[36] Ryan JE,Lynch AC,Phillips WA.Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.Colorectal Dis2016;18:234-46

[37] Martin ST,Winter DC.Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.Br J Surg2012;99:918-28

[38] University of Birmingham. Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer? (STAR-TREC). ClinicalTrials.gov Identifier: NCT02945566

[39] Foster JD,Smart NJ,Longman RJ,Francis N.Reconstruction of the perineum following extra-levator abdomino-perineal excision for carcinoma of the lower rectum - a systematic review.Colorectal Dis2012;14:1052-9

[40] Smart N,Longman R.Perineal reconstruction after abdominoperineal excision using inferior gluteal artery perforator flaps (Br J Surg 2012; 99: 584-588).Br J Surg2012;99:1165-6; author reply 1166