Nonoperative management of rectal cancer is an emerging treatment approach that aims to enable carefully selected patients to avoid the morbidity of radical surgical resection, while benefiting from the same excellent rates of tumor control achieved with radical surgery–based combined-modality therapy. The success of nonoperative management in this setting is based on the accurate assessment of tumor eradication after chemoradiotherapy, without pathologic verification. Therefore, clinical evidence of complete response—based on physical examination, endoscopic procedures, and imaging—must be utilized as a marker to predict for pathologic complete response and thus help select the patients who are most appropriate for nonoperative management. Initial evidence from retrospective and prospective single-arm and cohort studies has demonstrated high rates of local control and disease-free survival with nonoperative management of rectal cancer, compared with historical results of combined-modality therapy. Several trials and registries are prospectively investigating nonoperative management vs standard treatment of rectal cancer. At this time, combined-modality therapy with total mesorectal excision remains the standard of care for patients with locally advanced rectal cancer; nonoperative management should not be routinely offered outside of clinical trials.
Clinical Data Supporting Nonoperative Management of Rectal Cancer
The nonoperative management of rectal cancer was initiated in 2004, through the pioneering work of Habr-Gama et al at the University of São Paulo School of Medicine. These investigators evaluated patients with resectable distal rectal cancer treated with neoadjuvant CRT to 50.4 Gy, retrospectively comparing the long-term results of 71 patients who achieved cCR after CRT without further surgery vs outcomes in 22 patients who underwent resection for clinical partial response (cPR) after CRT but ultimately were found to have achieved pCR. The OS and DFS rates at 5 years were 88% and 83% in the surgical cohort (in which 16 of the 22 patients underwent a definitive colostomy or diverting temporary ileostomy) and 100% and 92% in the nonoperative cohort, respectively. Table 2 outlines outcomes of selected trials of nonoperative management of rectal cancer.
An expanded analysis confirmed these findings in 99 patients with sustained cCR after 12 months following neoadjuvant therapy who were managed nonoperatively. The authors reported a 13% recurrence rate; 5% had local recurrence, 7% had systemic recurrence, and 1% had both local and systemic recurrence. All local recurrences were successfully salvaged with surgery. Similar to the original results, in the expanded analysis, rates of 5-year OS and DFS were favorable, at 93% and 85%, respectively. In 2014, results were expanded further to include 183 patients; 90 (49%) of these patients demonstrated a cCR after neoadjuvant CRT and were followed with nonoperative management. Seventeen (19%) patients experienced a recurrence within 12 months after receiving CRT, highlighting the need for close surveillance in the immediate posttreatment period. Nevertheless, successful salvage was possible for 93% of the patients with local recurrences. The reported overall rate of local disease control was 94% after salvage surgery, with a 78% rate of organ preservation at 5-year follow-up for the 90 patients who were managed nonoperatively.
Another group from the National Institute of Cancer of Brazil, led by Araujo et al, conducted a separate retrospective analysis of disease recurrence in 42 patients who were managed nonoperatively, compared with 69 patients who had pCR after undergoing surgical resection. After 47 months of follow-up, overall recurrence rates were 28% in patients who received nonoperative management and 12% in surgically managed patients; isolated local recurrence rates in the nonoperatively vs surgically managed patients were 11% and 1.4%, respectively. Nonoperatively managed patients had a local control rate of 81%, and 80% of the patients who experienced isolated local relapse were surgically salvaged. Although no statistically significant difference in OS was found (71.6% with nonoperative management vs 89.9% with surgery), the DFS outcomes favored the surgical group (82.8% vs 60.9% with nonoperative management), leading the authors to caution against routine use of nonoperative management of rectal cancer outside of the clinical trial setting.
Similar to the Brazilian experience, an Australian group retrospectively analyzed long-term outcomes of 48 patients with potentially resectable rectal cancer who underwent neoadjuvant therapy but not surgery, due to medical inoperability or refusal. There was a 56% rate of cCR after neoadjuvant CRT or long-course RT alone, with over half of the patients free from progression after 5 years. As might be expected, the rates of progression-free survival and OS were lower than those reported by the Brazilian studies, since patients in the Australian study were generally elderly and frail, with a subset receiving RT without chemotherapy. Overall, the Brazilian and Australian trials introduced the concept of nonsurgical management of distal rectal cancer after long-course CRT as an alternative strategy for patients with cCR. The outcomes of these trials also provided evidence that high rates of long-term local control of rectal cancer could be achieved with nonoperative approaches. The seminal work of the Habr-Gama group in Brazil has spurred further interest in nonoperative management of rectal cancer through prospective cohort studies, large-scale population-based studies, and randomized prospective clinical trials.
Continuing their effort to characterize outcomes of nonoperative management of distal rectal cancer, Habr-Gama et al tested a more intensive neoadjuvant CRT regimen in a prospective single-arm study of 70 patients. Neoadjuvant treatment consisted of 54 Gy of RT and 6 cycles of 5-FU/leucovorin (with 3 cycles delivered concurrently and 3 delivered after RT). Patients were assessed for tumor response at 10 weeks after completion of RT. Initially, 47 (68%) patients presented with cCR, but 8 (17%) developed early tumor regrowth within the first 12 months of follow-up. Ultimately, 39 (57%) maintained a sustained cCR beyond 12 months. There were 4 (10%) cases of late recurrences, all of which were successfully salvaged by surgery. The 3-year OS rate was 94%, including a 51% rate of organ preservation.
In a small prospective study, Maas et al, from Maastricht University Medical Centre in the Netherlands, evaluated a policy of “wait and see” rather than surgery post RT for rectal cancer (Table 3). A total of 21 patients with rectal cancer who achieved cCR after neoadjuvant CRT were followed with MRI and endoscopy with biopsies without surgery. Functionality and outcomes in the wait-and-see group were compared with those of a control group of 20 patients who achieved pCR after neoadjuvant CRT and TME. Among the 21 wait-and-see patients, 20 (95%) were free from disease at a mean follow-up of 25 months; a single patient had a local recurrence and underwent salvage surgery. The control group had 2-year DFS and OS rates of 93% and 91%, respectively. Also in the Netherlands, Appelt et al conducted a single-institutional, prospective, single-arm, observational trial of high-dose CRT (RT at 60 Gy in 30 fractions to tumor, 50 Gy in 30 fractions to elective lymph nodes, a 5-Gy endorectal brachytherapy boost, and concomitant tegafur-uracil) and watchful waiting to determine the proportion of patients with resectable T2–T3 lower rectal cancers who can be managed nonoperatively. Of 51 eligible patients who were treated with high-dose CRT, 40 (78%) patients achieved cCR and underwent watchful waiting, with local recurrence rates of 15.5% and 25.9% at 1 year and 2 years, respectively. Posttreatment sphincter preservation rates were excellent: 72% at 1 year and 69% at 2 years. All patients in the study were alive at 2 years. The authors concluded that high-dose definitive CRT could be a safe alternative to APR for patients with distal rectal cancer.
Given that the majority of prior evidence supporting nonoperative management of rectal cancer with watch-and-wait approaches has been derived from retrospective, single-institutional, or noncomparative studies, Renehan et al from the United Kingdom sought to prospectively assess oncologic outcomes of nonoperative management of rectal cancer in patients achieving cCR. Their OnCoRe study was a propensity score–matched cohort analysis of patients with nonmetastatic rectal cancer treated with neoadjuvant CRT (45 Gy in 25 fractions with concurrent fluoropyrimidine-based chemotherapy). A total of 129 patients who had cCR after CRT were offered nonoperative management and were compared one-to-one with paired cohorts of patients who underwent surgical resection using propensity score matching. The rate of local recurrence at 3-year follow-up was 34% for patients managed nonoperatively, and 88% of the nonmetastatic locally recurrent tumors were salvageable. There were no significant differences in 3-year DFS rates (88% with watch and wait vs 78% with surgery) and OS rates (96% vs 87%, respectively); nonoperatively managed patients had better rates of colostomy-free survival than surgical patients, with a 26% absolute difference in avoidance of permanent colostomy at 3 years. This UK population–based matched cohort analysis further affirmed that many patients with rectal cancer managed by a nonoperative watch-and-wait approach could avoid major surgery and permanent colostomy, without compromising local control.
- Nonoperative management of rectal cancer aims to maintain excellent tumor control while avoiding the morbidity of radical surgery.
- The clinical response to upfront chemoradiation is utilized to select patients who are most appropriate for nonoperative management.
- Retrospective and limited prospective evidence suggests that nonoperative management results in high rates of local control and diseasefree survival compared with historical rates from combined-modality therapy. This is being explored in prospective registry and randomized studies.
- Combined-modality therapy remains the standard of care for locally advanced rectal cancer. Nonoperative management should not be offered outside of clinical trials.
Although a large proportion of the data supporting nonoperative management of rectal cancer originated outside of the United States, JD Smith et al retrospectively analyzed outcomes in 32 patients with stage I to III rectal cancer managed nonoperatively after achieving a cCR. At a median follow-up of 28 months, there was an 18.8% rate of local failure; all cases were controlled by salvage surgery, with no further local recurrence. The 2-year rates of DFS (88% vs 98%) and OS (96% vs 100%) were similar between the nonoperatively managed patients and a comparative cohort who underwent standard TME and achieved pCR. In an expanded and updated comparative analysis of 73 patients managed nonoperatively after cCR vs 72 patients who achieved pCR after surgery, 4-year disease-specific survival (91% vs 96%) and OS (91% vs 95%) were similar, with a 72% rate of rectal preservation in the nonoperatively managed cohort. Therefore, the authors concluded that in a highly selected group of patients with cCR to neoadjuvant therapy, nonoperative management in combination with salvage surgery, if necessary, could achieve oncologic outcomes similar to those of patients with a pCR after resection.
Nonoperative management of rectal cancer is under active investigation. Investigators from Memorial Sloan Kettering Cancer Center on behalf of the OSTRiCh (Optimizing the Surgical Treatment of Rectal Cancer) Consortium are leading a multi-institutional phase II study (ClinicalTrials.gov identifier: NCT02008656) of the efficacy of total neoadjuvant CRT with induction vs consolidation chemotherapy with FOLFOX or CAPOX (capecitabine and oxaliplatin), followed by observation for patients who achieve cCR and TME for patients with residual tumor. Although the treatment randomization in this trial is not specifically between nonoperative management and TME, the goal is to compare rates of 3-year DFS in a large population of patients with locally advanced rectal cancer, analyzing clinical outcomes of patients with cCR managed nonoperatively vs those with pCR after TME. In addition, an ongoing prospective randomized phase II trial (ClinicalTrials.gov identifier: NCT02052921) has been opened by the Instituto do Câncer do Estado de São Paulo (ICESP) in Brazil, comparing a watch-and-wait (nonoperative) approach vs surgery in patients with locally advanced rectal cancer who achieve a cCR after neoadjuvant CRT.
Overall, the nonoperative management approach pioneered by the Brazilian ICESP group has emerged as an attractive alternative for patients who are medically unfit for, or want to avoid, surgery. The initial retrospective evidence from the Brazilian Group[40-42] demonstrates local control and DFS outcomes similar to those of patients who achieve a pCR after neoadjuvant CRT and surgery. Prospective single-arm protocols and cohort analyses have affirmed the feasibility of this approach, with a prospective single-arm study demonstrating an especially high cCR rate of 68%. Current prospective comparison trials (including the ICESP study) directly address the question of benefit from nonoperative management in a randomized fashion. In addition, the International Watch & Wait database is an initiative to prospectively register all patients with rectal cancer managed nonoperatively, with the intention of accruing a dataset large enough to reduce confounding and bias, in order to assess long-term outcomes of nonoperative management. The most recent update from this database provides preliminary outcomes data: in 679 patients with cCR after induction therapy (90% managed with CRT), local control and OS rates at 3 years were 75% and 91%, respectively. Across all patients, the imaging surveillance protocol after therapy was variable, with 64%, 25%, and 6% of patients evaluated with MRI, CT, or endorectal ultrasound, respectively. Given the heterogeneity in induction therapy techniques and follow-up imaging strategies, the authors commented that collection of more data from this registry is necessary to determine the oncologic safety of omitting surgery.
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7-30.
2. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Rectal cancer. Version 3.2017. Updated March 13, 2017. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed July 6, 2017.
3. MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet. 1993;341:457-60.
4. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731-40.
5. Sauer R, Liersch T, Merkel S, et al. 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. J Clin Oncol. 2012;30:1926-33.
6. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93:1215-23.
7. Ngan SY, Burmeister B, Fisher RJ, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012; 30:3827-33.
8. Luna-Pérez P, Rodríguez-Ramírez S, Vega J, et al. Morbidity and mortality following abdominoperineal resection for low rectal adenocarcinoma. Rev Invest Clin. 2001;53:
9. Hendren SK, O’Connor BI, Liu M, et al. Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg. 2005;242:212-23.
10. Aschele C, Cionini L, Lonardi S, et al. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011;29:2773-80.
11. Gérard JP, Azria D, Gourgou-Bourgade S, et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010;28:1638-44.
12. Rödel C, Graeven U, Fietkau R, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:979-89.
13. Roh MS, Colangelo LH, O’Connell MJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124-30.
14. Garcia-Aguilar J, Chow OS, Smith DD, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16:957-66.
15. Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835-44.
16. Zorcolo L, Rosman AS, Restivo A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. 2012;19:2822-32.
17. Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99:918-28.
18. Goodman KA. Definitive chemoradiotherapy (“watch-and-wait” approach). Semin Radiat Oncol. 2016;26:205-10.
19. Habr-Gama A, São Julião GP, Perez RO. Nonoperative management of rectal cancer: identifying the ideal patients. Hematol Oncol Clin North Am. 2015;29:135-51.
20. Tulchinsky H, Shmueli E, Figer A, et al. An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol. 2008;15:2661-7.
21. Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009; 250:582-9.
22. Francois Y, Nemoz CJ, Baulieux J, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol. 1999;17:2396.
23. Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2016;263:458-64.
24. Sloothaak DA, Geijsen DE, van Leersum NJ, et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2013;100:933-9.
25. Lefevre JH, Mineur L, Kotti S, et al. Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in rectal cancer: a multicenter, randomized, controlled trial (GRECCAR-6). J Clin Oncol. 2016 Jul 18. [Epub ahead of print]
26. Guillem JG, Chessin DB, Shia J, et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point. J Clin Oncol. 2005; 23:3475-9.
27. Perez RO, Habr-Gama A, Pereira GV, et al. Role of biopsies in patients with residual rectal cancer following neoadjuvant chemoradiation after downsizing: can they rule out persisting cancer? Colorectal Dis. 2012;14:714-20.
28. Smith FM, Chang KH, Sheahan K, et al. The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy. Br J Surg. 2012; 99:993-1001.
29. De Nardi P, Carvello M. How reliable is current imaging in restaging rectal cancer after neoadjuvant therapy? World J Gastroenterol. 2013;19:5964-72.
30. Guillem JG, Ruby JA, Leibold T, et al. Neither FDG-PET nor CT can distinguish between a pathological complete response and an incomplete response after neoadjuvant chemoradiation in locally advanced rectal cancer: a prospective study. Ann Surg. 2013;258:289-95.
31. Pomerri F, Pucciarelli S, Maretto I, et al. Prospective assessment of imaging after preoperative chemoradiotherapy for rectal cancer. Surgery. 2011;149:56-64.
32. Maretto I, Pomerri F, Pucciarelli S, et al. The potential of restaging in the prediction of pathologic response after preoperative chemoradiotherapy for rectal cancer. Ann Surg Oncol. 2007;14:455-61.
33. Maffione AM, Marzola MC, Capirci C, et al. Value of 18F-FDG PET for predicting response to neoadjuvant therapy in rectal cancer: systematic review and meta-analysis. Am J Roentgenol. 2015;204:1261-8.
34. Perez RO, Habr-Gama A, São Julião GP, et al. Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks? Int J Radiat Oncol Biol Phys. 2012;84:1159-65.
35. Lambregts DM, Vandecaveye V, Barbaro B, et al. Diffusion-weighted MRI for selection of complete responders after chemoradiation for locally advanced rectal cancer: a multicenter study. Ann Surg Oncol. 2011;18:2224-31.
36. Lambregts DM, Rao SX, Sassen S, et al. MRI and diffusion-weighted MRI volumetry for identification of complete tumor responders after preoperative chemoradiotherapy in patients with rectal cancer: a bi-institutional validation study. Ann Surg. 2015;262:1034-9.
37. Kim DJ, Kim JH, Lim JS, et al. Restaging of rectal cancer with MR imaging after concurrent chemotherapy and radiation therapy. Radiographics. 2010;30:503-16.
38. van Heeswijk MM, Lambregts DM, Palm WM, et al. DWI for assessment of rectal cancer nodes after chemoradiotherapy: is the absence of nodes at DWI proof of a negative nodal status? AJR Am J Roentgenol. 2017;208:W79-W84.
39. Perez RO, São Julião GP, Habr-Gama A, et al. The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer. Dis Colon Rectum. 2009;52:1137-43.
40. Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711-7.
41. Habr-Gama A, Perez RO, Proscurshim I, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10:1319-28.
42. Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88:822-8.
43. Araujo RO, Valadão M, Borges D, et al. Nonoperative management of rectal cancer after chemoradiation opposed to resection after complete clinical response: a comparative study. Eur J Surg Oncol. 2015;41:1456-63.
44. Lim L, Chao M, Shapiro J, et al. Long-term outcomes of patients with localized rectal cancer treated with chemoradiation or radiotherapy alone because of medical inoperability or patient refusal. Dis Colon Rectum. 2007;50:2032-9.
45. Habr-Gama A, Sabbaga J, Gama-Rodrigues J, et al. Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum. 2013;56:1109-17.
46. Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29:4633-40.
47. Appelt AL, Pløen J, Harling H, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16:919-27.
48. Renehan AG, Malcomson L, Emsley R, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol. 2016;17:174-83.
49. Smith JD, Ruby JA, Goodman KA, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256:965-72.
50. Smith JJ, Chow OS, Eaton A, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. J Clin Oncol. 2015;33(suppl 3):abstr 509.
51. Smith JJ, Chow OS, Gollub MJ, et al. Organ preservation in rectal adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer. 2015;15:767.
52. Breugom AJ, van de Velde CJ. Is it time for watchful waiting for rectal cancer? Lancet Oncol. 2015;16:875-6.
53. van der Valk M; International Watch and Wait Database Consortium. The International Watch & Wait database (IWWD) for rectal cancer: an update. J Clin Oncol. 2017;35(suppl 4S):abstr 521.
54. National Institutes of Health consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA. 1990;264:1444-50.
55. Goodman KA, Patton CE, Fisher GA, et al. Appropriate customization of radiation therapy for stage II and III rectal cancer: executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method. Pract Radiat Oncol. 2016;6:166-75.
56. Allal AS, Bieri S, Pelloni A, et al. Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes.
Br J Cancer. 2000;82:1131-7.
57. Kasparek MS, Hassan I, Cima RR, et al. Quality of life after coloanal anastomosis and abdominoperineal resection for distal rectal cancers: sphincter preservation vs quality of life. Colorectal Dis. 2011;13:872-7.
58. Habr-Gama A, Lynn PB, Jorge JM, et al. Impact of organ-preserving strategies on anorectal function in patients with distal rectal cancer following neoadjuvant chemoradiation. Dis Colon Rectum. 2016;59:264-9.
59. van der Stok EP, Spaander MCW, Grünhagen DJ, et al. Surveillance after curative treatment for colorectal cancer. Nat Rev Clin Oncol. 2017;14:297-315.