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Downstaging Without Complete Pathologic Response After Neoadjuvant Treatment Improves Cancer Outcomes for cIII but not cII Rectal Cancers

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to evaluate whether downstaging impacts prognosis in patients with cII versus cIII rectal cancer.

Materials and Methods

We identified from our colorectal cancer database 295 patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI who received 5-FU-based chemoradiation followed by R0 surgery after a median interval of 7 weeks during 1997–2007. The median radiotherapy dose was 5040 cGy. We excluded 58 patients with pathologic complete response (pCR) and compared among the remaining 162 patients pathologic downstaging (cII to ypI, cIII to ypII or ypI) versus no pathologic downstaging (c stage ≤ yp stage). Outcomes evaluated were 5-year overall survival, 3-year cancer-specific survival, disease-free survival, overall recurrence, local recurrence, and distant recurrence.

Results

The median age was 58 years and median follow-up was 48 months. Patients with downstaging versus no downstaging were statistically comparable with respect to demographics, chemoradiation regimen, interval time between neoadjuvant chemoradiation and surgery, tumor distance from anal verge, surgical procedures performed, and follow-up time. With the exception of local recurrence rates, downstaging resulted in significantly improved cancer outcomes for cIII but not cII.

Conclusions

Downstaging without pCR is a significant prognostic factor for patients with stage cIII rectal cancer. Tumor response to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with cIII rectal cancer.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  3. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.

    Article  CAS  PubMed  Google Scholar 

  4. 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. 2007;67:369–77.

    PubMed  Google Scholar 

  5. 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.

    PubMed  Google Scholar 

  6. Quah HM, Chou JF, Gonen M, Shia J, Schrag D, Saltz LB, et al. Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer. 2008;113:57–64.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  8. Meade PG, Blatchford GJ, Thorson AG, Christensen MA, Ternent CA. Preoperative chemoradiation downstages locally advanced ultrasound-staged rectal cancer. Am J Surg. 1995;170:609–12; discussion 612–3.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. Habr-Gama A, Perez RO, Nadalin W, Nahas SC, Ribeiro U Jr, Silva E Sousa AH Jr, et al. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005;9:90–9; discussion 99–101.

    Article  PubMed  Google Scholar 

  14. Kuo LJ, Liu MC, Jian JJ, Horng CF, Cheng TI, Chen CM, et al. Is final TNM staging a predictor for survival in locally advanced rectal cancer after preoperative chemoradiation therapy? Ann Surg Oncol. 2007;14:2766–72.

    Article  PubMed  Google Scholar 

  15. Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–96.

    Article  PubMed  Google Scholar 

  16. Theodoropoulos G, Wise WE, Padmanabhan A, Kerner BA, Taylor CW, Aguilar PS, et al. T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum. 2002;45:895–903.

    Article  PubMed  Google Scholar 

  17. Lavery IC, Lopez-Kostner F, Pelley RJ, Fine RM. Treatment of colon and rectal cancer. Surg Clin North Am. 2000;80:535–69, ix.

    Article  CAS  PubMed  Google Scholar 

  18. Kalady MF, Campos-Lobato LF, Stocchi L, Geisler DP, Dietz D, Lavery IC, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250:582–9.

    Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. Lavery IC, Lopez-Kostner F, Fazio VW, Ferndandez-Martin M, Milsom JW, Church JM, et al. Chances of cure are not compromised with sphincter-saving procedures for cancer of the lower third of the rectum. Surgery. 1997;122:779–84; discussion 784–5.

    Article  CAS  PubMed  Google Scholar 

  21. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, et al. AJCC cancer staging manual. New York: Springer; 2002.

    Book  Google Scholar 

  22. Washington K, Berlin J, Branton P, Burgart LJ, Carter DK, Fitzgibbons PL, et al. Protocol for the examination of specimens from patients with primary carcinomas of the colon and rectum. Arch Pathol Lab Med. 2008;132:1182–93.

    PubMed  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. Wiig JN, Larsen SG, Dueland S, Giercksky KE. Clinical outcome in patients with complete pathologic response (pT0) to preoperative irradiation/chemo-irradiation operated for locally advanced or locally recurrent rectal cancer. J Surg Oncol. 2005;92:70–5.

    Article  PubMed  Google Scholar 

  25. Valentini V, Coco C, Picciocchi A, Morganti AG, Trodella L, Ciabattoni A, et al. Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys. 2002;53:664–74.

    PubMed  Google Scholar 

  26. Diaz-Gonzalez JA, Calvo FA, Cortes J, Garcia-Sabrido JL, Gomez-Espi M, Del Valle E, et al. Prognostic factors for disease-free survival in patients with T3–4 or N+ rectal cancer treated with preoperative chemoradiation therapy, surgery, and intraoperative irradiation. Int J Radiat Oncol Biol Phys. 2006;64:1122–8.

    PubMed  Google Scholar 

  27. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.

    Article  CAS  PubMed  Google Scholar 

  28. Wheeler JM, Dodds E, Warren BF, Cunningham C, George BD, Jones AC, et al. Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: correlation with rectal cancer regression grade. Dis Colon Rectum. 2004;47:2025–31.

    Article  CAS  PubMed  Google Scholar 

  29. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  Google Scholar 

  32. Vergo M, Nimieri H, Benson ABI. Adjuvant chemotherapy after neoadjuvant chemoradiation and surgery: A quest to improve survival for stage II and III rectal cancer. Curr Colorectal Cancer Rep. 2009;5:151–7.

    Article  Google Scholar 

  33. Watanabe T. Chemoradiotherapy and adjuvant chemotherapy for rectal cancer. Int J Clin Oncol. 2008;13:488–97.

    Article  CAS  PubMed  Google Scholar 

  34. Watanabe T, Komuro Y, Kiyomatsu T, Kanazawa T, Kazama Y, Tanaka J, et al. Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res. 2006;66:3370–4.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    CAS  PubMed  Google Scholar 

  36. Ghadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, et al. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol. 2005;23:1826–38.

    Article  CAS  PubMed  Google Scholar 

  37. Salerno G, Daniels IR, Moran BJ, Wotherspoon A, Brown G. Clarifying margins in the multidisciplinary management of rectal cancer: the MERCURY experience. Clin Radiol. 2006;61:916–23.

    Article  CAS  PubMed  Google Scholar 

  38. Brown G, Daniels IR. Preoperative staging of rectal cancer: the MERCURY research project. Recent Results Cancer Res 2005;165:58–74.

    Article  CAS  PubMed  Google Scholar 

  39. Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, 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: 2396–0.

    CAS  PubMed  Google Scholar 

  40. 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;15:2661–7.

    Article  PubMed  Google Scholar 

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Acknowledgment

We would like to acknowledge Dr. Amandio Soares, from Oncomed-Belo Horizonte/Brazil, for being the ASCO member sponsoring this paper presentation at ASCO 2009.

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Authors and Affiliations

  1. Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA

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

  2. Department of Cancer Biology, Cleveland Clinic, Cleveland, OH, USA

    Matthew F. Kalady MD

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  1. Luiz Felipe de Campos-Lobato MD
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  2. Luca Stocchi MD
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  9. Victor W. Fazio MD
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Correspondence to Luca Stocchi MD.

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de Campos-Lobato, L.F., Stocchi, L., da Luz Moreira, A. et al. Downstaging Without Complete Pathologic Response After Neoadjuvant Treatment Improves Cancer Outcomes for cIII but not cII Rectal Cancers. Ann Surg Oncol 17, 1758–1766 (2010). https://doi.org/10.1245/s10434-010-0924-4

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  • DOI: https://doi.org/10.1245/s10434-010-0924-4

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