Skip to main content

Advertisement

SpringerLink
Log in

Predictive clinicopathologic factors for limited response of T3 rectal cancer to combined modality therapy

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

The response of T3 rectal cancer to combined modality therapy (CMT) is highly predictive of long-term outcome following surgery. The aim of this study was to identify pretreatment factors associated with poor tumor response to neoadjuvant chemoradiation.

Methods

A prospective institutional database at Memorial Sloan-Kettering Cancer Center was queried for endorectal ultrasound (ERUS) stage T3N0–2 rectal cancer patients, treated with CMT followed by surgical resection, between 1998 and 2003. Preoperative clinicopathologic factors determined by biopsy, ERUS, proctoscopy, and digital rectal examination were correlated with the degree of downstaging of the primary mural lesion (tumor downstaging) in response to neoadjuvant therapy. Associations were analyzed by chi-square, Kaplan–Meier, and logistic regression.

Results

Of 274 patients, 51% obtained tumor downstaging in response to preoperative treatment, i.e., lower pathologic T-stage compared with pretreatment ERUS. Five-year recurrence-free survival was 89% in the cohort that obtained tumor downstaging compared with only 45% in the cohort that obtained no tumor downstaging. Factors significantly associated with limited or lack of tumor downstaging after CMT included: fixed tumor on digital rectal examination (p < 0.021), near-circumferential tumor (p < 0.011), tumor stenosis (p < 0.025), metastatic disease (p < 0.012), biopsy-proven poorly differentiated pathology (p < 0.002), and radial extension >2.5 mm on ERUS (p < 0.031). On multivariate analysis, deep radial extension on ERUS, metastatic disease, and poorly differentiated pathology were in each, independently associated with limited or lack of tumor downstaging.

Conclusions

Pretreatment evaluation with biopsy, proctoscopy, and ERUS can identify T3 rectal cancer patients unlikely to respond well to CMT. These patients may be considered for alternative protocols and their tumors studied to ascertain the molecular events responsible for resistance to chemoradiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. NIH Consensus Conference (1990) Adjuvant therapy for patients with colon and rectal cancer. JAMA 264:1444–1450

    Article  Google Scholar 

  2. Moertel CG, Fleming TR, Macdonald JS et al (1990) Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322:352–358

    Article  PubMed  CAS  Google Scholar 

  3. Moertel CG, Fleming TR, Macdonald JS et al (1995) Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 122:321–326

    PubMed  CAS  Google Scholar 

  4. Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  PubMed  CAS  Google Scholar 

  5. Guillem JG, Chessin DB, Cohen AM et al (2005) Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 241:829–836

    Article  PubMed  Google Scholar 

  6. Theodoropoulos G, Wise WE, Padmanabhan A et al (2002) 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 45:895–903

    Article  PubMed  Google Scholar 

  7. Hildebrandt U, Feifel G (1985) Preoperative staging of rectal cancer by intrarectal ultrasound. Dis Colon Rectum 28:42–46

    Article  PubMed  CAS  Google Scholar 

  8. Stipa F, Zernecke A, Moore HG et al (2004) Residual mesorectal lymph node involvement following neoadjuvant combined-modality therapy: rationale for radical resection. Ann Surg Oncol 11:187–191

    Article  PubMed  Google Scholar 

  9. Read TE, McNevin MS, Gross EK et al (2001) Neoadjuvant therapy for adenocarcinoma of the rectum: tumor response and acute toxicity. Dis Colon Rectum 44:513–522

    Article  PubMed  CAS  Google Scholar 

  10. Stipa F, Chessin DB, Shia J et al (2006) 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 13:1047–1053

    Article  PubMed  Google Scholar 

  11. Willett CG, Badizadegan K, Ancukiewicz M, Shellito PC (1999) Prognostic factors in stage T3N0 rectal cancer: do all patients require postoperative pelvic irradiation and chemotherapy? Dis Colon Rectum 42:167–173

    Article  PubMed  CAS  Google Scholar 

  12. Das P, Skibber JM, Rodriguez-Bigas MA et al (2007) Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 109:1750–1755

    Article  PubMed  CAS  Google Scholar 

  13. Kwok H, Bissett IP, Hill GL (2000) Preoperative staging of rectal cancer. Int J Colorectal Dis 15:9–20

    Article  PubMed  CAS  Google Scholar 

  14. Ueno H, Mochizuki H, Tamakuma S (1998) Prognostic significance of extranodal microscopic foci discontinuous with primary lesion in rectal cancer. Dis Colon Rectum 41:55–61

    Article  PubMed  CAS  Google Scholar 

  15. Valentini V, Coco C, Cellini N et al (1998) Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation. Int J Radiat Oncol Biol Phys 40:1067–1075

    Article  PubMed  CAS  Google Scholar 

  16. Vuong T, Belliveau PJ, Michel RP et al (2002) Conformal preoperative endorectal brachytherapy treatment for locally advanced rectal cancer: early results of a phase I/II study. Dis Colon Rectum 45:1486–1493

    Article  PubMed  Google Scholar 

  17. Jakobsen A, Mortensen JP, Bisgaard C et al (2006) Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost. Int J Radiat Oncol Biol Phys 64:461–465

    Article  PubMed  Google Scholar 

  18. Chau I, Cunningham D (2006) Adjuvant therapy in colon cancer—what, when and how? Ann Oncol 17:1347–1359

    Article  PubMed  CAS  Google Scholar 

  19. Minsky B O’Reilly E, Wong WD et al (1999) Daily low-dose irinotecan (CPT-11) plus pelvic irradiation as preoperative treatment of locally advanced rectal cancer. Proc Am Soc Clin Oncol 18:266a[Meeting Abstract]

    Google Scholar 

  20. Mehta VK, Cho C, Ford JM et al (2003) Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer. Int J Radiat Oncol Biol Phys 55:132–137

    Article  PubMed  Google Scholar 

  21. Zhu AX, Willett CG (2005) Combined modality treatment for rectal cancer. Semin Oncol 32:103–112

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA

    Anne Y. Lin, W. Douglas Wong, Larissa K. Temple, José G. Guillem, Philip B. Paty & Martin R. Weiser

  2. Pathology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA

    Jinru Shia

  3. Radiation Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA

    Bruce D. Minsky

Authors
  1. Anne Y. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Douglas Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinru Shia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bruce D. Minsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Larissa K. Temple
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José G. Guillem
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Philip B. Paty
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martin R. Weiser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin R. Weiser.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, A.Y., Wong, W.D., Shia, J. et al. Predictive clinicopathologic factors for limited response of T3 rectal cancer to combined modality therapy. Int J Colorectal Dis 23, 243–249 (2008). https://doi.org/10.1007/s00384-007-0406-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-007-0406-8

Keywords

Search

Navigation