Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2011

01-06-2011 | Gastrointestinal Oncology

Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer Decreases Distant Recurrence and Could Eradicate Local Recurrence

Authors: Luiz Felipe de Campos-Lobato, MD, Luca Stocchi, MD, Andre da Luz Moreira, MD, Daniel Geisler, MD, David W. Dietz, MD, Ian C. Lavery, MD, Victor W. Fazio, MD, Matthew F. Kalady, MD

Published in: Annals of Surgical Oncology | Issue 6/2011

Login to get access

Abstract

Background

The aim of this study was to evaluate the clinical implications of pathologic complete response (pCR) (i.e., T0N0M0) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer.

Materials and Methods

A single-center, prospectively maintained colorectal cancer database was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007. Patients were stratified into pCR and no-pCR groups and compared with respect to demographics, tumor and treatment characteristics, and oncologic outcomes. Outcomes evaluated were 5-year overall survival, disease-free survival, disease-specific mortality, local recurrence, and distant recurrence.

Results

The query returned 238 patients (73% male), with a median age of 57 years and median follow-up of 54 months. Of these, 58 patients achieved pCR. Patients with pCR vs no-pCR were statistically comparable with respect to demographics, chemoradiation regimens, tumor distance from anal verge, clinical stage, surgical procedures performed, and follow-up time. No patient with pCR had local recurrence. Overall survival and distant recurrence were also significantly improved for patients achieving pCR.

Conclusions

Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer. Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population.
Literature
1.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRef
2.
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;351:1731–40.PubMedCrossRef
3.
Bujko K, Michalski W, Kepka L, Nowacki MP, Nasierowska-Guttmejer A, Tokar P, et al. Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: an analysis of outcomes in a randomized trial. Int J Radiat Oncol Biol Phys. 20071;67:369–77.
4.
Chan AK, Wong A, Jenken D, Heine J, Buie D, Johnson D. Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys. 2005;61:665–77.PubMedCrossRef
5.
Minsky BD, Cohen AM, Enker WE, Saltz L, Guillem JG, Paty PB, et al. Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer. Int J Radiat Oncol Biol Phys. 1997;37:289–95.PubMedCrossRef
6.
Rouanet P, Fabre JM, Dubois JB, Dravet F, Saint Aubert B, Pradel J, et al. Conservative surgery for low rectal carcinoma after high-dose radiation. functional and oncologic results. Ann Surg. 1995;221:67–73.PubMedCrossRef
7.
Stipa F, Chessin DB, Shia J, Paty PB, Weiser M, Temple LK, et al. A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography. Ann Surg Oncol. 2006;13:1047–53.PubMedCrossRef
8.
Mehta VK, Poen J, Ford J, Edelstein PS, Vierra M, Bastidas AJ, et al. Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 or T4 rectal cancer. Dis Colon Rectum. 2001;44:52–8.PubMedCrossRef
9.
Kim JS, Kim JS, Cho MJ, Song KS, Yoon WH. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2002;54:403–8.PubMedCrossRef
10.
Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005;241:829–36; discussion 836–8.PubMedCrossRef
11.
Bosset JF, Magnin V, Maingon P, Mantion G, Pelissier EP, Mercier M, et al. Preoperative radiochemotherapy in rectal cancer: long-term results of a phase II trial. Int J Radiat Oncol Biol Phys. 2000;46:323–7.PubMedCrossRef
12.
de Campos-Lobato LF, Stocchi L, da Luz Moreira A, Kalady MF, Geisler D, Dietz D, et al. Downstaging without complete pathologic response after neoadjuvant treatment improves cancer outcomes for cIII but not cII rectal cancers. Ann Surg Oncol. 2010;17:1758–66.PubMedCrossRef
13.
Lavery IC, Lopez-Kostner F, Pelley RJ, Fine RM. Treatment of colon and rectal cancer. Surg Clin North Am. 2000;80:535–69, ix.PubMedCrossRef
14.
Lopez-Kostner F, Lavery IC, Hool GR, Rybicki LA, Fazio VW. Total mesorectal excision is not necessary for cancers of the upper rectum. Surgery. 1998;124:612–7; discussion 617–8.PubMedCrossRef
15.
Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1:1479–82.PubMedCrossRef
16.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti III A. AJCC—Cancer Staging Manual. 7th ed., New York: Springer; 2010.
17.
Greene FL, Page DL, Fleming ID, Fritz AG, Balch MC, Haller DG, et al. AJCC Cancer Staging Manual. New York: Springer; 2002.CrossRef
18.
Pocock SJ, Clayton TC, Altman DG. Survival plots of time-to-event outcomes in clinical trials: good practice and pitfalls. Lancet. 2002;359:1686–9.PubMedCrossRef
19.
Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. New York: John Wiley & Sons, Inc.; 2000.CrossRef
20.
21.
Wibe A, Moller B, Norstein J, Carlsen E, Wiig JN, Heald RJ, et al. A national strategic change in treatment policy for rectal cancer–implementation of total mesorectal excision as routine treatment in Norway. A national audit. Dis Colon Rectum. 2002;45:857–66.PubMedCrossRef
22.
Carlsen E, Schlichting E, Guldvog I, Johnson E, Heald RJ. Effect of the introduction of total mesorectal excision for the treatment of rectal cancer. Br J Surg. 1998;85:526–9.PubMedCrossRef
23.
Schlichting E, Carlsen E. Introduction of a new surgical technique in rectal cancer. Tidsskr Nor Laegeforen. 1998;118:1846–9.PubMed
24.
Wiig JN, Carlsen E, Soreide O. Mesorectal excision for rectal cancer: A view from Europe. Semin Surg Oncol. 1998;15:78–86.PubMedCrossRef
25.
Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European organisation for research and treatment of cancer radiation oncology group. J Clin Oncol. 2007;25:4379–86.PubMedCrossRef
26.
Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991;324:709–15.PubMedCrossRef
27.
Hurst PA, Prout WG, Kelly JM, Bannister JJ, Walker RT. Local recurrence after low anterior resection using the staple gun. Br J Surg. 1982;69:275–6.PubMedCrossRef
28.
Goligher JC, Dukes CE, Bussey HJ. Local recurrences after sphincter saving excisions for carcinoma of the rectum and rectosigmoid. Br J Surg. 1951;39:199–211.PubMedCrossRef
29.
NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA. 1990;264:1444–50.
30.
Capirci C, Valentini V, Cionini L, De Paoli A, Rodel C, Glynne-Jones R, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys. 2008;72:99–107.PubMedCrossRef
31.
Hahnloser D, Nelson H, Gunderson LL, Hassan I, Haddock MG, O’Connell MJ, et al. Curative potential of multimodality therapy for locally recurrent rectal cancer. Ann Surg. 2003;237:502–8.PubMed
32.
Pacelli F, Tortorelli AP, Rosa F, Bossola M, Sanchez AM, Papa V, et al. Locally recurrent rectal cancer: prognostic factors and long-term outcomes of multimodal therapy. Ann Surg Oncol. 2010;17:152–62.PubMedCrossRef
33.
Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007;246:693–701.PubMedCrossRef
34.
Ahmad NR, Nagle D. Long-term results of preoperative radiation therapy alone for stage T3 and T4 rectal cancer. Br J Surg. 1997;84:1445–8.PubMedCrossRef
35.
Garcia-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA. A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum. 2003;46:298–304.PubMedCrossRef
36.
Onaitis MW, Noone RB, Fields R, Hurwitz H, Morse M, Jowell P, et al. Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. Ann Surg Oncol. 2001;8:801–6.PubMedCrossRef
37.
Pucciarelli S, Toppan P, Friso ML, Russo V, Pasetto L, Urso E, et al. Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome. Dis Colon Rectum. 2004;47:1798–807.PubMedCrossRef
38.
Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Pudelko M, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol. 2004;72:15–24.PubMedCrossRef
39.
Messick CA, Sanchez J, Dejulius KL, Church JM, Kalady MF. Genetic and molecular diversity of colon cancer hepatic metastases. Surgery. 2009;146:227–31.PubMedCrossRef
40.
Kalady MF, de Campos-Lobato LF, Stocchi L, Geisler D, Dietz D, Lavery IC, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250:582–9.PubMed
41.
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;15:2261–7.CrossRef
42.
de Campos-Lobato LF, Geisler D, da Luz Moreira A, Stocchi L, Dietz D, Kalady MF. Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery. J Gastrointest Surg. 2010 [Epub ahead of print].
43.
44.
Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.PubMedCrossRef
45.
Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5.PubMedCrossRef
46.
Borschitz T, Wachtlin D, Mohler M, Schmidberger H, Junginger T. Neoadjuvant chemoradiation and local excision for T2–3 rectal cancer. Ann Surg Oncol. 2008;15:712–20.PubMedCrossRef
47.
Bonnen MD, Ballo MT, Myers JN, Garden AS, Diaz EM, Jr, Gershenwald JE, et al. Elective radiotherapy provides regional control for patients with cutaneous melanoma of the head and neck. Cancer. 2004;100:383–9.PubMedCrossRef
48.
Borschitz T. In reply: local excision as an optional tool to individualize treatment of rectal cancer. Ann Surg Oncol. 2008;15:2630–1.CrossRef
49.
Hershman MJ, Myint AS, Makin CA. Multi-modality approach in curative local treatment of early rectal carcinomas. Colorectal Dis. 2003;5:445–50.PubMedCrossRef
50.
Kim CJ, Yeatman TJ, Coppola D, Trotti A, Williams B, Barthel JS, et al. Local excision of T2 and T3 rectal cancers after downstaging chemoradiation. Ann Surg. 2001;234:352–8; discussion 358–9.PubMedCrossRef
51.
Lezoche E, Guerrieri M, Paganini AM, Baldarelli M, De Sanctis A, Lezoche G. Long-term results in patients with T2-3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery. Br J Surg. 2005;92:1546–52.PubMedCrossRef
52.
Tjandra T. Long-term results in patients with T2-3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery. Tech Coloproctol. 2006;10:158; discussion 158–9.PubMedCrossRef
53.
Ruo L, Guillem JG, Minsky BD, Quan SH, Paty PB, Cohen AM. Preoperative radiation with or without chemotherapy and full-thickness transanal excision for selected T2 and T3 distal rectal cancers. Int J Colorectal Dis. 2002;17:54–8.PubMedCrossRef
54.
Schell SR, Zlotecki RA, Mendenhall WM, Marsh RW, Vauthey JN, Copeland EM, 3rd. Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy. J Am Coll Surg. 2002;194:584–90; discussion 590–1.PubMedCrossRef
55.
Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Jr, Silva e Sousa AH, Jr, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711–7; discussion 717–8.PubMed
56.
Mignanelli E, de Campos-Lobato L, Stocchi L, Lavery I, Dietz D. Downstaging following CRT for locally advanced rectal cancer: is there more (tumor) than meets the eye? Dis Colon Rectum. 2010;53:251–6. PubMedCrossRef
57.
Ratto C, Valentini V, Morganti AG, Barbaro B, Coco C, Sofo L, et al. Combined-modality therapy in locally advanced primary rectal cancer. Dis Colon Rectum. 2003;46:59–67.PubMedCrossRef
58.
Zmora O, Dasilva GM, Gurland B, Pfeffer R, Koller M, Nogueras JJ, et al. Does rectal wall tumor eradication with preoperative chemoradiation permit a change in the operative strategy? Dis Colon Rectum. 2004;47:1607–12.PubMedCrossRef
59.
Grann A, Minsky BD, Cohen AM, Saltz L, Guillem JG, Paty PB, et al. Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer. Dis Colon Rectum. 1997;40:515–22.PubMedCrossRef
60.
de la Torre A, Ramos S, Valcarcel FJ, Candal A, Regueiro CA, Romero J, et al. Phase II study of radiochemotherapy with UFT and low-dose oral leucovorin in patients with unresectable rectal cancer. Int J Radiat Oncol Biol Phys. 1999;45:629–34.CrossRef
61.
Seong J, Cho JH, Kim NK, Min JS, Suh CO. Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer. Int J Radiat Oncol Biol Phys. 2001;50:435–9.PubMedCrossRef
62.
Hiotis SP, Weber SM, Cohen AM, Minsky BD, Paty PB, Guillem JG, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg. 2002;194:131–5; discussion 135–6.PubMedCrossRef
63.
O’Neill BD, Brown G, Heald RJ, Cunningham D, Tait DM. Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer. Lancet Oncol. 2007;8:625–33.PubMedCrossRef
64.
Watanabe T. Chemoradiotherapy and adjuvant chemotherapy for rectal cancer. Int J Clin Oncol. 2008;13:488–97.PubMedCrossRef
65.
Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from national surgical adjuvant breast and bowel project protocol C-03. J Clin Oncol. 1993;11:1879–87.PubMed
66.
Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK. Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol. 2010;28:264–71.PubMedCrossRef
67.
Tjandra JJ, Kilkenny JW, Buie WD, Hyman N, Simmang C, Anthony T, et al. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum. 2005;48:411–23.PubMedCrossRef
68.
Baxter NN, Virnig DJ, Rothenberger DA, Morris AM, Jessurun J, Virnig BA. Lymph node evaluation in colorectal cancer patients: a population-based study. J Natl Cancer Inst. 2005;97:219–25.PubMedCrossRef
69.
70.
de la Fuente SG, Manson RJ, Ludwig KA, Mantyh CR. Neoadjuvant chemoradiation for rectal cancer reduces lymph node harvest in proctectomy specimens. J Gastrointest Surg. 2009;13:269–74.CrossRef
71.
Habr-Gama A, Perez RO, Proscurshim I, Rawet V, Pereira DD, Sousa AH, et al. Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean? Dis Colon Rectum. 2008;51:277–83.PubMedCrossRef
Metadata
Title
Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer Decreases Distant Recurrence and Could Eradicate Local Recurrence
Authors
Luiz Felipe de Campos-Lobato, MD
Luca Stocchi, MD
Andre da Luz Moreira, MD
Daniel Geisler, MD
David W. Dietz, MD
Ian C. Lavery, MD
Victor W. Fazio, MD
Matthew F. Kalady, MD
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1506-1

Other articles of this Issue 6/2011

Annals of Surgical Oncology 6/2011 Go to the issue

Gastrointestinal Oncology

Hyperthermic Intraperitoneal Chemotherapy in Advanced Gastric Cancer: The End of Skepticism?

Bone and Soft Tissue Sarcomas

Navigating Risk Stratification Systems for the Management of Patients With GIST

Hepatobiliary Tumors

Medium-Sized (3.1–5.0 cm) Hepatocellular Carcinoma: Transarterial Chemoembolization Plus Radiofrequency Ablation Versus Radiofrequency Ablation Alone

Hepatobiliary Tumors

Continuous Occlusion of Hepatic Artery Proper for Prevention of Blood Loss in Partial Hepatectomy for Ruptured Hepatocellular Carcinoma: A Case-Matched Comparative Study

Gastrointestinal Oncology

Aggressive Surgical Approach for Patients with T4 Gastric Carcinoma: Promise or Myth?

Head and Neck Oncology

Recurrent Laryngeal Nerve Diameter Increases During Thyroidectomy