Clin Colon Rectal Surg 2017; 30(05): 387-394
DOI: 10.1055/s-0037-1606116
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management of the Complete Clinical Response

Angelita Habr-Gama
1   Angelita & Joaquim Gama Institute, Sao Paulo, SP, Brazil
2   University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil
,
Guilherme Pagin São Julião
1   Angelita & Joaquim Gama Institute, Sao Paulo, SP, Brazil
,
Bruna Borba Vailati
1   Angelita & Joaquim Gama Institute, Sao Paulo, SP, Brazil
,
Ivana Castro
1   Angelita & Joaquim Gama Institute, Sao Paulo, SP, Brazil
,
Debora Raffaele
1   Angelita & Joaquim Gama Institute, Sao Paulo, SP, Brazil
› Author Affiliations
Further Information

Publication History

Publication Date:
27 November 2017 (online)

Abstract

Organ preservation is considered in the management of selected patients with rectal cancer. Complete clinical response observed after neoadjuvant chemoradiation for rectal cancer is one of these cases. Patients who present complete clinical response are candidates to the watch-and-wait approach, when radical surgery is not immediately performed and is offered only to patients in the event of a local relapse. These patients are included in a strict follow-up, and up of 70% of them will never be operated during the follow-up. This strategy is associated with similar oncological outcomes as patients operated on, and the advantage of avoiding the morbidity associated to the radical operation. In this article we will discuss in detail the best candidates for this approach, the protocol itself, and the long-term outcomes.

 
  • Reference

  • 1 Kosinski L, Habr-Gama A, Ludwig K, Perez R. Shifting concepts in rectal cancer management: a review of contemporary primary rectal cancer treatment strategies. CA Cancer J Clin 2012; 62 (03) 173-202
  • 2 Sanghera P, Wong DW, McConkey CC, Geh JI, Hartley A. Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response. Clin Oncol (R Coll Radiol) 2008; 20 (02) 176-183
  • 3 Habr-Gama A, Lynn PB, Jorge JMN. , et al. Impact of organ-preserving strategies on anorectal function in patients with distal rectal cancer following neoadjuvant chemoradiation. Dis Colon Rectum 2016; 59 (04) 264-269
  • 4 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 (04) 822-828
  • 5 Smith FM, Rao C, Oliva Perez R. , et al. Avoiding radical surgery improves early survival in elderly patients with rectal cancer, demonstrating complete clinical response after neoadjuvant therapy: results of a decision-analytic model. Dis Colon Rectum 2015; 58 (02) 159-171
  • 6 Habr-Gama A, São Julião GP, Perez RO. Nonoperative management of rectal cancer: identifying the ideal patients. Hematol Oncol Clin North Am 2015; 29 (01) 135-151
  • 7 Smith FM, Waldron D, Winter DC. Rectum-conserving surgery in the era of chemoradiotherapy. Br J Surg 2010; 97 (12) 1752-1764
  • 8 Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum 2010; 53 (12) 1692-1698
  • 9 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 (04) 711-717 , discussion 717–718
  • 10 Lopes-Ramos C, Koyama FC, Habr-Gama A. , et al. Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer. Cancer Genet 2015; 208 (06) 319-326
  • 11 Brettingham-Moore KH, Duong CP, Greenawalt DM. , et al. Pretreatment transcriptional profiling for predicting response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma. Clin Cancer Res 2011; 17 (09) 3039-3047
  • 12 Watanabe T, Kobunai T, Akiyoshi T, Matsuda K, Ishihara S, Nozawa K. Prediction of response to preoperative chemoradiotherapy in rectal cancer by using reverse transcriptase polymerase chain reaction analysis of four genes. Dis Colon Rectum 2014; 57 (01) 23-31
  • 13 Rimkus C, Friederichs J, Boulesteix AL. , et al. Microarray-based prediction of tumor response to neoadjuvant radiochemotherapy of patients with locally advanced rectal cancer. Clin Gastroenterol Hepatol 2008; 6 (01) 53-61
  • 14 Hardiman KM, Ulintz PJ, Kuick RD. , et al. Intra-tumor genetic heterogeneity in rectal cancer. Lab Invest 2016; 96 (01) 4-15
  • 15 Bettoni F, Masotti C, Habr-Gama A. , et al. Intratumoral genetic heterogeneity in rectal cancer: are single biopsies representative of the entirety of the tumor?. Ann Surg 2017; 265 (01) e4-e6
  • 16 Perez RO, Habr-Gama A, São Julião GP. , et al. Should we give up the search for a clinically useful gene signature for the prediction of response of rectal cancer to neoadjuvant chemoradiation?. Dis Colon Rectum 2016; 59 (09) 895-897
  • 17 Sauer R, Becker H, Hohenberger W. , et al; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351 (17) 1731-1740
  • 18 Kapiteijn E, Marijnen CA, Nagtegaal ID. , et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345 (09) 638-646
  • 19 van Gijn W, Marijnen CA, Nagtegaal ID. , et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011; 12 (06) 575-582
  • 20 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 (16) 1926-1933
  • 21 Peeters KC, van de Velde CJ, Leer JW. , et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study. J Clin Oncol 2005; 23 (25) 6199-6206
  • 22 Perez RO, Habr-Gama A, Gama-Rodrigues J. , et al. Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683). Cancer 2012; 118 (14) 3501-3511
  • 23 Garcia-Aguilar J, Shi Q, Thomas Jr CR. , 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 (02) 384-391
  • 24 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 (09) 1211-1218
  • 25 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 (10) 1109-1117
  • 26 Bosset JF, Calais G, Mineur L. , et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--EORTC 22921. J Clin Oncol 2005; 23 (24) 5620-5627
  • 27 Radu C, Berglund A, Påhlman L, Glimelius B. Short-course preoperative radiotherapy with delayed surgery in rectal cancer - a retrospective study. Radiother Oncol 2008; 87 (03) 343-349
  • 28 Wiltshire KL, Ward IG, Swallow C. , et al. Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival. Int J Radiat Oncol Biol Phys 2006; 64 (03) 709-716
  • 29 Jakobsen A, Ploen J, Vuong T, Appelt A, Lindebjerg J, Rafaelsen SR. Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer: a randomized trial comparing two radiation doses. Int J Radiat Oncol Biol Phys 2012; 84 (04) 949-954
  • 30 Gerard JP, Frin AC, Doyen J. , et al. Organ preservation in rectal adenocarcinoma (T1) T2-T3 Nx M0. Historical overview of the Lyon Sud - Nice experience using contact x-ray brachytherapy and external beam radiotherapy for 120 patients. Acta Oncol 2015; 54 (04) 545-551
  • 31 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 (08) 919-927
  • 32 Vuong T, Devic S, Podgorsak E. High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer. Clin Oncol (R Coll Radiol) 2007; 19 (09) 701-705
  • 33 Schrag D, Weiser MR, Goodman KA. , et al. Neoadjuvant FOLFOX-bev, without radiation, for locally advanced rectal cancer. J Clin Oncol 2010;28(suppl):abstr 3511
  • 34 Habr-Gama A, Fernandez LM, Perez RO. What more do we want from neoadjuvant treatment strategies in rectal cancer?. Colorectal Cancer 2015; 4: 1-4
  • 35 Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, São Julião GP, Gama-Rodrigues J. Increasing the rates of complete response to neoadjuvant chemoradiotherapy for distal rectal cancer: results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum 2009; 52 (12) 1927-1934
  • 36 Brown G. Thin section MRI in multidisciplinary pre-operative decision making for patients with rectal cancer. Br J Radiol 2005; 78 (Spec No 2): S117-S127
  • 37 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 (08) 2396
  • 38 Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M. 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 (10) 2661-2667
  • 39 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 (04) 582-589
  • 40 Evans J, Tait D, Swift I. , et al. Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial?. Dis Colon Rectum 2011; 54 (10) 1251-1259
  • 41 Wolthuis AM, Penninckx F, Haustermans K. , et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol 2012; 19 (09) 2833-2841
  • 42 Garcia-Aguilar J, Chow OS, Smith DD. , et al; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol 2015; 16 (08) 957-966
  • 43 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; (e-pub ahead of print). JCO676049
  • 44 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 (05) 1159-1165
  • 45 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 (06) 714-720
  • 46 Lambregts DM, Maas M, Bakers FC. , et al. Long-term follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. Dis Colon Rectum 2011; 54 (12) 1521-1528
  • 47 Patel UB, Taylor F, Blomqvist L. , et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol 2011; 29 (28) 3753-3760
  • 48 Patel UB, Brown G, Rutten H. , et al. Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol 2012; 19 (09) 2842-2852
  • 49 Nahas SC, Rizkallah Nahas CS, Sparapan Marques CF. , et al. Pathologic complete response in rectal cancer: can we detect it? Lessons learned from a proposed randomized trial of watch-and-wait treatment of rectal cancer. Dis Colon Rectum 2016; 59 (04) 255-263
  • 50 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 (03) 311-315
  • 51 Bhoday J, Smith F, Siddiqui MR. , et al. Magnetic resonance tumor regression grade and residual mucosal abnormality as predictors for pathological complete response in rectal cancer postneoadjuvant chemoradiotherapy. Dis Colon Rectum 2016; 59 (10) 925-933
  • 52 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 (08) 2224-2231
  • 53 Curvo-Semedo L, Lambregts DM, Maas M. , et al. Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging. Radiology 2011; 260 (03) 734-743
  • 54 Dos Anjos DA, Habr-Gama A, Vailati BB. , et al. (18)F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes. Ann Nucl Med 2016; 30 (08) 513-517
  • 55 Cascini GL, Avallone A, Delrio P. , et al. 18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med 2006; 47 (08) 1241-1248
  • 56 Kristiansen C, Loft A, Berthelsen AK. , et al. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer. Dis Colon Rectum 2008; 51 (01) 21-25
  • 57 Dos Anjos DA, Perez RO, Habr-Gama A. , et al. Semiquantitative volumetry by sequential PET/CT may improve prediction of complete response to neoadjuvant chemoradiation in patients with distal rectal cancer. Dis Colon Rectum 2016; 59 (09) 805-812
  • 58 Vaccaro CA, Yazyi FJ, Ojra Quintana G. , et al. Locally advanced rectal cancer: preliminary results of rectal preservation after neoadjuvant chemoradiotherapy [in Spanish]. Cir Esp 2016; 94 (05) 274-279
  • 59 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 (11) 1456-1463
  • 60 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 (35) 4633-4640
  • 61 Dalton RS, Velineni R, Osborne ME. , et al. A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management?. Colorectal Dis 2012; 14 (05) 567-571
  • 62 Smith RK, Fry RD, Mahmoud NN, Paulson EC. Surveillance after neoadjuvant therapy in advanced rectal cancer with complete clinical response can have comparable outcomes to total mesorectal excision. Int J Colorectal Dis 2015; 30 (06) 769-774
  • 63 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 (02) 174-183
  • 64 Martens MH, Maas M, Heijnen LA. , et al. Long-term outcome of an organ preservation program after neoadjuvant treatment for rectal cancer. J Natl Cancer Inst 2016; 108 (12) 108
  • 65 Habr-Gama A, Perez RO, Proscurshim I. , et al. Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome?. Int J Radiat Oncol Biol Phys 2008; 71 (04) 1181-1188
  • 66 Perez RO. Complete clinical response in rectal cancer: a turning tide. Lancet Oncol 2016; 17 (02) 125-126
  • 67 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 (09) 835-844