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01-08-2020 | Rectal Cancer | Review Article

Organ Preservation in Rectal Cancer

Authors: Jonathan B. Yuval, Hannah M. Thompson, Julio Garcia-Aguilar

Published in: Journal of Gastrointestinal Surgery | Issue 8/2020

Abstract

A proportion of patients with rectal cancer who undergo neoadjuvant treatment end up with a complete pathological response. Because these patients have excellent oncological outcomes, many have questioned if surgical treatment in this population constitutes overtreatment. There is growing interest in watch and wait with selective organ preservation for rectal cancer patients. We review the fundamentals and key considerations of this approach including patient selection, available treatment regimens, assessment of response, long-term monitoring of response, and long-term oncological and functional outcomes.

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40. https://doi.org/10.1056/NEJMoa040694.CrossRefPubMed

Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B et al. Colorectal cancer. Lancet. 2010;375(9719):1030–47. https://doi.org/10.1016/S0140-6736(10)60353-4.CrossRefPubMed

Pucciarelli S, Del Bianco P, Efficace F, Serpentini S, Capirci C, De Paoli A et al. Patient-reported outcomes after neoadjuvant chemoradiotherapy for rectal cancer: a multicenter prospective observational study. Ann Surg. 2011;253(1):71–7. https://doi.org/10.1097/SLA.0b013e3181fcb856.CrossRefPubMed

Chen TY, Wiltink LM, Nout RA, Meershoek-Klein Kranenbarg E, Laurberg S, Marijnen CA et al. Bowel function 14 years after preoperative short-course radiotherapy and total mesorectal excision for rectal cancer: report of a multicenter randomized trial. Clin Colorectal Cancer. 2015;14(2):106–14. https://doi.org/10.1016/j.clcc.2014.12.007.CrossRefPubMed

Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR 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. https://doi.org/10.1186/s12885-015-1632-z.CrossRefPubMedPubMedCentral

Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ 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(9):835–44. https://doi.org/10.1016/S1470-2045(10)70172-8.CrossRefPubMed

Garcia-Aguilar J, Shi Q, Thomas CR, Jr., Chan E, Cataldo P, Marcet J et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012;19(2):384–91. https://doi.org/10.1245/s10434-011-1933-7.CrossRefPubMed

Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957–66. https://doi.org/10.1016/S1470-2045(15)00004-2.CrossRefPubMedPubMedCentral

Park IJ, You YN, Agarwal A, Skibber JM, Rodriguez-Bigas MA, Eng C et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol. 2012;30(15):1770–6. https://doi.org/10.1200/JCO.2011.39.7901.CrossRefPubMedPubMedCentral

10.

Janeway H. Treatment of cancer, particularly of the tongue, tonsil and rectum, by buried emanation. Am J Roentgenol. 1920;7:92.

11.

Binkley GE. Radiation in the treatment of rectal cancer. Ann Surg. 1929;90(6):1000–14.https://doi.org/10.1097/00000658-192912000-00007.CrossRefPubMedPubMedCentral

12.

Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Jr., Silvae Sousa AH, Jr. et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711–7; discussion 7-8. https://doi.org/10.1097/01.sla.0000141194.27992.32.CrossRefPubMedPubMedCentral

13.

Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40. https://doi.org/10.1200/JCO.2011.37.7176.CrossRefPubMed

14.

Araujo RO, Valadao M, Borges D, Linhares E, de Jesus JP, Ferreira CG 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(11):1456–63. https://doi.org/10.1016/j.ejso.2015.08.156.CrossRefPubMed

15.

Martens MH, Maas M, Heijnen LA, Lambregts DM, Leijtens JW, Stassen LP et al. Long-term outcome of an organ preservation program after neoadjuvant treatment for rectal cancer. J Natl Cancer Inst. 2016;108(12). https://doi.org/10.1093/jnci/djw171.

16.

Appelt AL, Ploen J, Harling H, Jensen FS, Jensen LH, Jorgensen JC et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16(8):919–27. https://doi.org/10.1016/S1470-2045(15)00120-5.CrossRefPubMed

17.

Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256(6):965–72. https://doi.org/10.1097/SLA.0b013e3182759f1c.CrossRefPubMed

18.

Ayloor Seshadri R, Kondaveeti SS, Jayanand SB, John A, Rajendranath R, Arumugam V et al. Complete clinical response to neoadjuvant chemoradiation in rectal cancers: can surgery be avoided? Hepatogastroenterology. 2013;60(123):410–4. https://doi.org/10.5754/hge12354.CrossRefPubMed

19.

Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS 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(2):174–83. https://doi.org/10.1016/S1470-2045(15)00467-2.CrossRefPubMed

20.

Smith JJ, Strombom P, Chow OS, Roxburgh CS, Lynn P, Eaton A et al. Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy. JAMA Oncol. 2019;5(4):e185896. https://doi.org/10.1001/jamaoncol.2018.5896.CrossRefPubMedPubMedCentral

21.

Habr-Gama A, Sao Juliao GP, Vailati BB, Sabbaga J, Aguilar PB, Fernandez LM et al. Organ preservation in cT2N0 rectal cancer after neoadjuvant chemoradiation therapy: the impact of radiation therapy dose-escalation and consolidation chemotherapy. Ann Surg. 2019;269(1):102–7. https://doi.org/10.1097/SLA.0000000000002447.CrossRefPubMed

22.

Lezoche E, Baldarelli M, Lezoche G, Paganini AM, Gesuita R, Guerrieri M. Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg. 2012;99(9):1211–8. https://doi.org/10.1002/bjs.8821.CrossRefPubMed

23.

Elmessiry MM, Van Koughnett JA, Maya A, DaSilva G, Wexner SD, Bejarano P et al. Local excision of T1 and T2 rectal cancer: proceed with caution. Colorectal Dis. 2014;16(9):703–9. https://doi.org/10.1111/codi.12657.CrossRefPubMed

24.

Swedish Rectal Cancer T, Cedermark B, Dahlberg M, Glimelius B, Pahlman L, Rutqvist LE et al. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336(14):980–7. https://doi.org/10.1056/NEJM199704033361402.CrossRef

25.

Fiorica F, Trovo M, Anania G, Marcello D, Di Benedetto F, Marzola M et al. Is it possible a conservative approach after radiochemotherapy in locally advanced rectal cancer (LARC)? A systematic review of the literature and meta-analysis. J Gastrointest Cancer. 2019;50(1):98–108. https://doi.org/10.1007/s12029-017-0041-8.CrossRefPubMed

26.

Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. 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(10):1215–23. https://doi.org/10.1002/bjs.5506.CrossRefPubMed

27.

Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D 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(31):3827–33. https://doi.org/10.1200/JCO.2012.42.9597.CrossRefPubMed

28.

Bujko K, Pietrzak L, Partycki M, Szczepkowski M, Wyrwicz L, Rupinski M et al. The feasibility of short-course radiotherapy in a watch-and-wait policy for rectal cancer. Acta Oncol. 2017;56(9):1152–4. https://doi.org/10.1080/0284186X.2017.1327721.CrossRefPubMed

29.

Cummings MA, Usuki KY, Fleming FJ, Tejani MA, Katz AW. Short course radiation therapy for rectal cancer in the elderly: can radical surgery be avoided? J Gastrointest Oncol. 2019;10(2):357–61. https://doi.org/10.21037/jgo.2018.09.05.CrossRefPubMedPubMedCentral

30.

Jia AY, Narang A, Safar B, Zaheer A, Murphy A, Azad NS et al. Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma. Radiat Oncol. 2019;14(1):147. https://doi.org/10.1186/s13014-019-1358-1.CrossRefPubMedPubMedCentral

31.

Nilsson PJ, van Etten B, Hospers GA, Pahlman L, van de Velde CJ, Beets-Tan RG et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial. BMC Cancer. 2013;13:279. https://doi.org/10.1186/1471-2407-13-279.CrossRefPubMedPubMedCentral

32.

Appelt AL, Ploen J, Vogelius IR, Bentzen SM, Jakobsen A. Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013;85(1):74–80. https://doi.org/10.1016/j.ijrobp.2012.05.017.CrossRefPubMed

33.

Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071. https://doi.org/10.1001/jamaoncol.2018.0071.CrossRefPubMedPubMedCentral

34.

Fokas E, Allgauer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R et al. Randomized phase II trial of chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12. J Clin Oncol. 2019;37(34):3212–22. https://doi.org/10.1200/JCO.19.00308.CrossRefPubMed

35.

Probst CP, Becerra AZ, Aquina CT, Tejani MA, Wexner SD, Garcia-Aguilar J et al. Extended intervals after neoadjuvant therapy in locally advanced rectal cancer: the key to improved tumor response and potential organ preservation. J Am Coll Surg. 2015;221(2):430–40. https://doi.org/10.1016/j.jamcollsurg.2015.04.010.CrossRefPubMedPubMedCentral

36.

Du D, Su Z, Wang D, Liu W, Wei Z. Optimal interval to surgery after neoadjuvant chemoradiotherapy in rectal cancer: a systematic review and meta-analysis. Clin Colorectal Cancer. 2018;17(1):13–24. https://doi.org/10.1016/j.clcc.2017.10.012.CrossRefPubMed

37.

Erlandsson J, Holm T, Pettersson D, Berglund A, Cedermark B, Radu C et al. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017;18(3):336–46. https://doi.org/10.1016/S1470-2045(17)30086-4.CrossRefPubMed

38.

Pettersson D, Lorinc E, Holm T, Iversen H, Cedermark B, Glimelius B et al. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg. 2015;102(8):972–8; discussion 8. https://doi.org/10.1002/bjs.9811.CrossRefPubMedPubMedCentral

39.

Akgun E, Caliskan C, Bozbiyik O, Yoldas T, Sezak M, Ozkok S et al. Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2018;105(11):1417–25. https://doi.org/10.1002/bjs.10984.CrossRefPubMed

40.

Huang Y, Lee D, Young C. Predictors for complete pathological response for stage II and III rectal cancer following neoadjuvant therapy - a systematic review and meta-analysis. Am J Surg. 2020. https://doi.org/10.1016/j.amjsurg.2020.01.001.

41.

Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109(9):1750–5. https://doi.org/10.1002/cncr.22625.CrossRefPubMed

42.

Garcia-Aguilar J, Chen Z, Smith DD, Li W, Madoff RD, Cataldo P et al. Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer. Ann Surg. 2011;254(3):486–92; discussion 92-3. https://doi.org/10.1097/SLA.0b013e31822b8cfa.CrossRefPubMedPubMedCentral

43.

Chow OS, Kuk D, Keskin M, Smith JJ, Camacho N, Pelossof R et al. KRAS and combined KRAS/TP53 mutations in locally advanced rectal cancer are independently associated with decreased response to neoadjuvant therapy. Ann Surg Oncol. 2016;23(8):2548–55. https://doi.org/10.1245/s10434-016-5205-4.CrossRefPubMedPubMedCentral

44.

Chen MB, Wu XY, Yu R, Li C, Wang LQ, Shen W et al. P53 status as a predictive biomarker for patients receiving neoadjuvant radiation-based treatment: a meta-analysis in rectal cancer. PLoS One. 2012;7(9):e45388. https://doi.org/10.1371/journal.pone.0045388.CrossRefPubMedPubMedCentral

45.

de Rosa N, Rodriguez-Bigas MA, Chang GJ, Veerapong J, Borras E, Krishnan S et al. DNA mismatch repair deficiency in rectal cancer: benchmarking its impact on prognosis, neoadjuvant response prediction, and clinical cancer genetics. J Clin Oncol. 2016;34(25):3039–46. https://doi.org/10.1200/JCO.2016.66.6826.CrossRefPubMedPubMedCentral

46.

McCoy MJ, Hemmings C, Miller TJ, Austin SJ, Bulsara MK, Zeps N et al. Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer. Br J Cancer. 2015;113(12):1677–86. https://doi.org/10.1038/bjc.2015.427.CrossRefPubMedPubMedCentral

47.

Akiyoshi T, Tanaka N, Kiyotani K, Gotoh O, Yamamoto N, Oba K et al. Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer. Br J Surg. 2019;106(10):1381–92. https://doi.org/10.1002/bjs.11179.CrossRefPubMed

48.

Matsutani S, Shibutani M, Maeda K, Nagahara H, Fukuoka T, Nakao S et al. Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer. Cancer Sci. 2018;109(4):966–79. https://doi.org/10.1111/cas.13542.CrossRefPubMedPubMedCentral

49.

Maas M, Lambregts DM, Nelemans PJ, Heijnen LA, Martens MH, Leijtens JW et al. Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI: selection for organ-saving treatment. Ann Surg Oncol. 2015;22(12):3873–80. https://doi.org/10.1245/s10434-015-4687-9.CrossRefPubMedPubMedCentral

50.

van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018;391(10139):2537–45. https://doi.org/10.1016/S0140-6736(18)31078-X.CrossRefPubMed

51.

Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2(7):501–13. https://doi.org/10.1016/S2468-1253(17)30074-2.CrossRefPubMed

52.

Guillem JG, Chessin DB, Shia J, Moore HG, Mazumdar M, Bernard B et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point. J Clin Oncol. 2005;23(15):3475–9. https://doi.org/10.1200/JCO.2005.06.114.CrossRefPubMed

53.

Smith FM, Wiland H, Mace A, Pai RK, Kalady MF. Clinical criteria underestimate complete pathological response in rectal cancer treated with neoadjuvant chemoradiotherapy. Dis Colon Rectum. 2014;57(3):311–5. https://doi.org/10.1097/DCR.0b013e3182a84eba.CrossRefPubMed

54.

Lambregts DMJ, Delli Pizzi A, Lahaye MJ, van Griethuysen JJM, Maas M, Beets GL et al. A pattern-based approach combining tumor morphology on MRI with distinct signal patterns on diffusion-weighted imaging to assess response of rectal tumors after chemoradiotherapy. Dis Colon Rectum. 2018;61(3):328–37. https://doi.org/10.1097/DCR.0000000000000915.CrossRefPubMed

55.

Kong JC, Guerra GR, Warrier SK, Ramsay RG, Heriot AG. Outcome and salvage surgery following "Watch and Wait" for rectal cancer after neoadjuvant therapy: a systematic review. Dis Colon Rectum. 2017;60(3):335–45. https://doi.org/10.1097/DCR.0000000000000754.CrossRefPubMed

56.

Gani C, Gani N, Zschaeck S, Eberle F, Schaeffeler N, Hehr T et al. Organ preservation in rectal cancer: the patients' perspective. Front Oncol. 2019;9:318. https://doi.org/10.3389/fonc.2019.00318.CrossRefPubMedPubMedCentral

57.

Schwartzberg DM, Grieco MJ, Timen M, Grucela AL, Bernstein MA, Wexner SD. Is the whole world watching and waiting? An International Questionnaire on the current practices of 'Watch & Wait' rectal cancer treatment. Colorectal Dis. 2018;20(12):1069. https://doi.org/10.1111/codi.14397.CrossRefPubMed

Title: Organ Preservation in Rectal Cancer
Authors: Jonathan B. Yuval
Hannah M. Thompson
Julio Garcia-Aguilar
Publication date: 01-08-2020
Publisher: Springer US
Keywords: Rectal Cancer
Rectal Cancer
Published in: Journal of Gastrointestinal Surgery / Issue 8/2020
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-020-04583-w

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Organ Preservation in Rectal Cancer

Abstract

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Abstract

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