Treatment of locally advanced unresectable or recurrent rectal adenocarcinoma
- Christopher G Willett, MD
Christopher G Willett, MD
- Section Editor — Radiation Therapy
- Duke University Medical School
- Miguel A Rodriguez-Bigas, MD
Miguel A Rodriguez-Bigas, MD
- Professor of Surgery
- MD Anderson Cancer Center
- David P Ryan, MD
David P Ryan, MD
- Associate Professor of Medicine
- Harvard Medical School
Approximately 40,000 Americans are diagnosed with rectal cancer annually . The vast majoprity of these are adenocarcinomas.
Surgical resection is the cornerstone of curative therapy for patients with early stage, potentially resectable rectal adenocarcinoma. The addition of radiation therapy (RT) and chemotherapy can enhance both local control and cure rates in patients with either transmural invasion or positive perirectal lymph nodes.
Such therapy is often administered preoperatively. While the only definitive indication for preoperative chemoradiotherapy is the presence of a T3 or T4 (table 1) rectal adenocarcinoma, other relative indications include a T1/2 lesion that is clinically node-positive, a distal tumor for which tumor regression may allow successful conversion of a planned APR to a sphincter-sparing surgical procedure, or if the preoperative staging evaluation suggests the presence of mesorectal invasion. While most of these patients are technically resectable at presentation, outcomes are better with preoperative chemoradiotherapy. (See "Neoadjuvant chemoradiotherapy and radiotherapy for rectal adenocarcinoma", section on 'Indications for neoadjuvant treatment'.)
In contrast, rectal squamous cell cancers are rare tumors that are difficult to distinguish from anal cancer. They are treated similarly to anal cancer with definitive chemoradiotherapy with surgery reserved for persistent or recurrent disease. Management of these tumors is addressed elsewhere. (See "Clinical features, staging, and treatment of anal cancer", section on 'Rectal squamous cell cancers'.)
DEFINITION OF LOCALLY ADVANCED DISEASE
Some patients with rectal adenocarcinoma present with more locally advanced or recurrent but nonmetastatic disease that cannot be easily resected. The criteria for unresectability are variable and not clearly defined. Some define a locally advanced tumor as one with endorectal ultrasound evidence of a T3/4 or N1 tumor, or one that is and/or clinically bulky .
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5.
- Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005; 241:829.
- Farouk R, Nelson H, Radice E, et al. Accuracy of computed tomography in determining resectability for locally advanced primary or recurrent colorectal cancers. Am J Surg 1998; 175:283.
- Beets-Tan RG, Beets GL, Borstlap AC, et al. Preoperative assessment of local tumor extent in advanced rectal cancer: CT or high-resolution MRI? Abdom Imaging 2000; 25:533.
- Dresen RC, Kusters M, Daniels-Gooszen AW, et al. Absence of tumor invasion into pelvic structures in locally recurrent rectal cancer: prediction with preoperative MR imaging. Radiology 2010; 256:143.
- Messiou C, Chalmers AG, Boyle K, et al. Pre-operative MR assessment of recurrent rectal cancer. Br J Radiol 2008; 81:468.
- Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001; 93:583.
- McGory ML, Shekelle PG, Ko CY. Development of quality indicators for patients undergoing colorectal cancer surgery. J Natl Cancer Inst 2006; 98:1623.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on April 01, 2014).
- Tjandra JJ, Kilkenny JW, Buie WD, et al. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum 2005; 48:411.
- Lopez MJ. Multivisceral resections for colorectal cancer. J Surg Oncol 2001; 76:1.
- Nakafusa Y, Tanaka T, Tanaka M, et al. Comparison of multivisceral resection and standard operation for locally advanced colorectal cancer: analysis of prognostic factors for short-term and long-term outcome. Dis Colon Rectum 2004; 47:2055.
- Rowe VL, Frost DB, Huang S. Extended resection for locally advanced colorectal carcinoma. Ann Surg Oncol 1997; 4:131.
- Lehnert T, Methner M, Pollok A, et al. Multivisceral resection for locally advanced primary colon and rectal cancer: an analysis of prognostic factors in 201 patients. Ann Surg 2002; 235:217.
- Luna-Pérez P, Rodríguez-Ramírez SE, De la Barrera MG, et al. Multivisceral resection for colon cancer. J Surg Oncol 2002; 80:100.
- Poeze M, Houbiers JG, van de Velde CJ, et al. Radical resection of locally advanced colorectal cancer. Br J Surg 1995; 82:1386.
- Govindarajan A, Coburn NG, Kiss A, et al. Population-based assessment of the surgical management of locally advanced colorectal cancer. J Natl Cancer Inst 2006; 98:1474.
- Pawlik TM, Skibber JM, Rodriguez-Bigas MA. Pelvic exenteration for advanced pelvic malignancies. Ann Surg Oncol 2006; 13:612.
- Balbay MD, Slaton JW, Trane N, et al. Rationale for bladder-sparing surgery in patients with locally advanced colorectal carcinoma. Cancer 1999; 86:2212.
- Yang TX, Morris DL, Chua TC. Pelvic exenteration for rectal cancer: a systematic review. Dis Colon Rectum 2013; 56:519.
- Law WL, Chu KW, Choi HK. Total pelvic exenteration for locally advanced rectal cancer. J Am Coll Surg 2000; 190:78.
- Hafner GH, Herrera L, Petrelli NJ. Morbidity and mortality after pelvic exenteration for colorectal adenocarcinoma. Ann Surg 1992; 215:63.
- Sagar PM, Gonsalves S, Heath RM, et al. Composite abdominosacral resection for recurrent rectal cancer. Br J Surg 2009; 96:191.
- WANG CC, SCHULZ MD. The role of radiation therapy in the management of carcinoma of the sigmoid, rectosigmoid, and rectum. Radiology 1962; 79:1.
- O'Connell MJ, Childs DS, Moertel CG, et al. A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma. Int J Radiat Oncol Biol Phys 1982; 8:1115.
- Brierley JD, Cummings BJ, Wong CS, et al. Adenocarcinoma of the rectum treated by radical external radiation therapy. Int J Radiat Oncol Biol Phys 1995; 31:255.
- Emami B, Pilepich M, Willett C, et al. Effect of preoperative irradiation on resectability of colorectal carcinomas. Int J Radiat Oncol Biol Phys 1982; 8:1295.
- Dosoretz DE, Gunderson LL, Hedberg S, et al. Preoperative irradiation for unresectable rectal and rectosigmoid carcinomas. Cancer 1983; 52:814.
- Mendenhall WM, Million RR, Bland KI, et al. Initially unresectable rectal adenocarcinoma treated with preoperative irradiation and surgery. Ann Surg 1987; 205:41.
- Stevens KR, Fletcher WS. High dose preoperative pelvic irradiation for unresectable adenocarcinoma of the rectum or sigmoid. Int J Radiat Oncol Biol Phys 1983; 9:148.
- Allee PE, Tepper JE, Gunderson LL, Munzenrider JE. Postoperative radiation therapy for incompletely resected colorectal carcinoma. Int J Radiat Oncol Biol Phys 1989; 17:1171.
- Schild SE, Martenson JA Jr, Gunderson LL, Dozois RR. Long-term survival and patterns of failure after postoperative radiation therapy for subtotally resected rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 1989; 16:459.
- Ghossein NA, Samala EC, Alpert S, et al. Elective postoperative radiotherapy after incomplete resection of colorectal cancer. Dis Colon Rectum 1981; 24:252.
- Whiting JF, Howes A, Osteen RT. Preoperative irradiation for unresectable carcinoma of the rectum. Surg Gynecol Obstet 1993; 176:203.
- Valentini V, Coco C, Rizzo G, et al. Outcomes of clinical T4M0 extra-peritoneal rectal cancer treated with preoperative radiochemotherapy and surgery: a prospective evaluation of a single institutional experience. Surgery 2009; 145:486.
- Mohiuddin M, Regine WF, John WJ, et al. Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys 2000; 46:883.
- Chan AK, Wong AO, Langevin J, et al. Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study. Int J Radiat Oncol Biol Phys 2000; 48:843.
- Janjan NA, Khoo VS, Abbruzzese J, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999; 44:1027.
- Videtic GM, Fisher BJ, Perera FE, et al. Preoperative radiation with concurrent 5-fluorouracil continuous infusion for locally advanced unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1998; 42:319.
- Braendengen M, Tveit KM, Berglund A, et al. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 2008; 26:3687.
- Mohiuddin M, Hayne M, Regine WF, et al. Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers. Int J Radiat Oncol Biol Phys 2000; 48:1075.
- Nakfoor BM, Willett CG, Shellito PC, et al. The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer. Ann Surg 1998; 228:194.
- Mathis KL, Nelson H, Pemberton JH, et al. Unresectable colorectal cancer can be cured with multimodality therapy. Ann Surg 2008; 248:592.
- Kim HK, Jessup JM, Beard CJ, et al. Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy. Int J Radiat Oncol Biol Phys 1997; 38:777.
- Roeder F, Treiber M, Oertel S, et al. Patterns of failure and local control after intraoperative electron boost radiotherapy to the presacral space in combination with total mesorectal excision in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2007; 67:1381.
- Kusters M, Holman FA, Martijn H, et al. Patterns of local recurrence in locally advanced rectal cancer after intra-operative radiotherapy containing multimodality treatment. Radiother Oncol 2009; 92:221.
- Hyngstrom JR, Tzeng CW, Beddar S, et al. Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience. J Surg Oncol 2014; 109:652.
- Shibata D, Guillem JG, Lanouette N, et al. Functional and quality-of-life outcomes in patients with rectal cancer after combined modality therapy, intraoperative radiation therapy, and sphincter preservation. Dis Colon Rectum 2000; 43:752.
- Lingareddy V, Ahmad NR, Mohiuddin M. Palliative reirradiation for recurrent rectal cancer. Int J Radiat Oncol Biol Phys 1997; 38:785.
- Hansen MH, Balteskard L, Dørum LM, et al. Locally recurrent rectal cancer in Norway. Br J Surg 2009; 96:1176.
- Tepper JE, O'Connell M, Hollis D, et al. Analysis of surgical salvage after failure of primary therapy in rectal cancer: results from Intergroup Study 0114. J Clin Oncol 2003; 21:3623.
- Henry LR, Sigurdson E, Ross EA, et al. Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome. Ann Surg Oncol 2007; 14:1081.
- Ferenschild FT, Vermaas M, Verhoef C, et al. Abdominosacral resection for locally advanced and recurrent rectal cancer. Br J Surg 2009; 96:1341.
- Bhangu A, Brown G, Akmal M, Tekkis P. Outcome of abdominosacral resection for locally advanced primary and recurrent rectal cancer. Br J Surg 2012; 99:1453.
- Colibaseanu DT, Mathis KL, Abdelsattar ZM, et al. Is curative resection and long-term survival possible for locally re-recurrent colorectal cancer in the pelvis? Dis Colon Rectum 2013; 56:14.
- Alberda WJ, Verhoef C, Nuyttens JJ, et al. Outcome in patients with resectable locally recurrent rectal cancer after total mesorectal excision with and without previous neoadjuvant radiotherapy for the primary rectal tumor. Ann Surg Oncol 2014; 21:520.
- Bouchard P, Efron J. Management of recurrent rectal cancer. Ann Surg Oncol 2010; 17:1343.
- Moore HG, Shoup M, Riedel E, et al. Colorectal cancer pelvic recurrences: determinants of resectability. Dis Colon Rectum 2004; 47:1599.
- Wasserberg N, Kaiser AM, Nunoo-Mensah JW, et al. Preservation of bowel and urinary continence in the management of locally recurrent rectal cancer. J Surg Oncol 2005; 92:76.
- Koda K, Tobe T, Takiguchi N, et al. Pelvic exenteration for advanced colorectal cancer with reconstruction of urinary and sphincter functions. Br J Surg 2002; 89:1286.
- Gunderson LL, Nelson H, Martenson JA, et al. Intraoperative electron and external beam irradiation with or without 5-fluorouracil and maximum surgical resection for previously unirradiated, locally recurrent colorectal cancer. Dis Colon Rectum 1996; 39:1379.
- Rades D, Kuhn H, Schultze J, et al. Prognostic factors affecting locally recurrent rectal cancer and clinical significance of hemoglobin. Int J Radiat Oncol Biol Phys 2008; 70:1087.
- Rödel C, Grabenbauer GG, Matzel KE, et al. Extensive surgery after high-dose preoperative chemoradiotherapy for locally advanced recurrent rectal cancer. Dis Colon Rectum 2000; 43:312.
- Stocchi L, Nelson H, Sargent DJ, et al. Is en-bloc resection of locally recurrent rectal carcinoma involving the urinary tract indicated? Ann Surg Oncol 2006; 13:740.
- Dresen RC, Gosens MJ, Martijn H, et al. Radical resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer. Ann Surg Oncol 2008; 15:1937.
- Alektiar KM, Zelefsky MJ, Paty PB, et al. High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer. Int J Radiat Oncol Biol Phys 2000; 48:219.
- Mannaerts GH, Martijn H, Crommelin MA, et al. Intraoperative electron beam radiation therapy for locally recurrent rectal carcinoma. Int J Radiat Oncol Biol Phys 1999; 45:297.
- Haddock MG, Miller RC, Nelson H, et al. Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer. Int J Radiat Oncol Biol Phys 2011; 79:143.
- Wallace HJ 3rd, Willett CG, Shellito PC, et al. Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer. J Surg Oncol 1995; 60:122.
- Mohiuddin M, Marks G, Marks J. Long-term results of reirradiation for patients with recurrent rectal carcinoma. Cancer 2002; 95:1144.
- Guren MG, Undseth C, Rekstad BL, et al. Reirradiation of locally recurrent rectal cancer: a systematic review. Radiother Oncol 2014; 113:151.
- Das P, Delclos ME, Skibber JM, et al. Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation. Int J Radiat Oncol Biol Phys 2010; 77:60.
- DEFINITION OF LOCALLY ADVANCED DISEASE
- PRETREATMENT EVALUATION
- Physical and endoscopic examination
- GENERAL SURGICAL PRINCIPLES
- Exenterative procedures
- - Outcomes
- TREATMENT OF LOCALLY ADVANCED DISEASE
- RT alone
- External beam RT and surgery
- - Postoperative RT
- - Preoperative RT
- Preoperative chemoradiotherapy
- - Infusional versus bolus 5-FU
- - Oral fluoropyrimidines
- - Newer approaches
- Intraoperative irradiation
- Benefit of postoperative chemotherapy
- LOCALLY RECURRENT RECTAL CANCER
- Surgical resection
- Combined modality therapy
- - Intraoperative RT
- - Previously irradiated patients
- - Adjuvant chemotherapy
- PALLIATION OF OBSTRUCTIVE SYMPTOMS DUE TO LOCALLY ADVANCED DISEASE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Treatment of locally advanced unresectable disease
- Management of locally recurrent rectal cancer