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Techniques in Coloproctology

, Volume 21, Issue 9, pp 745–754 | Cite as

One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer

  • M. A. Pereira
  • A. R. Dias
  • S. F. Faraj
  • C. S. R. Nahas
  • A. R. Imperiale
  • C. F. S. Marques
  • G. C. Cotti
  • B. C. Azevedo
  • S. C. Nahas
  • E. S. de Mello
  • U. RibeiroJr.
Original Article

Abstract

Background

Neoadjuvant chemoradiation therapy (nCRT) for rectal cancer may lead to cure. As we currently lack reliable methods to clinically confirm the absence of disease, some patients undergo radical resection and have pathological complete response (pCR) still undergo surgery. Furthermore, it is uncertain if conventional one-level histopathological analysis is accurate enough to determine complete response. Confirming pCR is essential to determine the prognosis and to consider the patient’s inclusion in trials of adjuvant therapy. The aim of this study was to determine whether the current 1-level approach is sufficient to confirm pCR.

Methods

Four hundred and thirty-five patients with rectal cancer who received nCRT followed by radical resection were analyzed. All cases identified as pCR by 1-level step section histological evaluation were reassessed with 3-level step sections and immunohistochemical analysis to verify the presence of residual disease.

Results

Out of 435 patients, 75 (17.2%) were staged as ypT0. Of these, 6 had lymph node involvement and 1 had distant metastasis, leaving 68 (15.6%) who had pCR. After the additional step sections, residual tumor was detected in 12 (17.6%) of these 68. The final pCR rate was 12.9%. Distant recurrence was detected in 7.1% of real-pCR patients compared to 16.7% in the false-pCR group (p = 0.291). Sensitivity of clinical assessment for detecting pCR was 35.7%, and the accuracy of 1-section histological evaluation to identify pCR was 82.4%.

Conclusions

Histopathological analysis with 1-level step section is insufficient to determine complete tumor eradication. The 3-level sections methodology revealed residual tumor cells in patients initially classified as ypT0. Further studies with larger sample size are required to verify the clinical relevance of these residual tumor cells. Caution should continue to be applied to watch and wait strategies following nCRT.

Keywords

Rectal cancer Complete response Neoadjuvant therapy Pathologic response Watch and wait 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the hospital ethics committee (Cancer Institute, HCFMUSP-ICESP Ethics Committee: 102/15), and all procedures followed were in accordance with the ethical standards.

Informed consent

For this type of study, formal consent is not required because the analysis used anonymous clinical data that were obtained by a medical database after each patient agreed to treatment by written consent.

References

  1. 1.
    Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740CrossRefPubMedGoogle Scholar
  2. 2.
    Martin ST, Heneghan HM, Winter DC (2012) Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg 99:918–928CrossRefPubMedGoogle Scholar
  3. 3.
    Glynne-Jones R, Hughes R (2012) Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg 99:897–909CrossRefPubMedGoogle Scholar
  4. 4.
    Rodel C, Martus P, Papadoupolos T et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696CrossRefPubMedGoogle Scholar
  5. 5.
    de Campos-Lobato LF, Stocchi L, da Luz Moreira A et al (2011) Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 18:1590–1598CrossRefPubMedGoogle Scholar
  6. 6.
    Habr-Gama A, Sabbaga J, Gama-Rodrigues J (2013) Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum 56(10):1109–1117CrossRefPubMedGoogle Scholar
  7. 7.
    Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J (2010) Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum 53:1692–1698CrossRefPubMedGoogle Scholar
  8. 8.
    Ryan JE, Warrier SK, Lynch AC, Heriot AG (2015) Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. Colorectal Dis 17(10):849–861CrossRefPubMedGoogle Scholar
  9. 9.
    Tang LH, Berlin J, Branton P, et al (2013) Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. College of American Pathologists (CAP), ColonRectumGoogle Scholar
  10. 10.
    Park SY, Chang HJ, Kim DY et al (2011) Is step section necessary for determination of complete pathological response in rectal cancer patients treated with preoperative chemoradiotherapy? Histopathology 59:650–659CrossRefPubMedGoogle Scholar
  11. 11.
    Nahas SC, Rizkallah Nahas CS, Sparapan Marques CF, Ribeiro U Jr, Cotti GC, Imperiale AR, Capareli FC, Chih Chen AT, Hoff PM, Cecconello I (2016) 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 59(4):255–263. doi: 10.1097/DCR.0000000000000558 CrossRefPubMedGoogle Scholar
  12. 12.
    American Joint Committee on Cancer (2010) AJCC cancer staging manual, 7th edn. Springer, New YorkCrossRefGoogle Scholar
  13. 13.
    Dias AR, Pereira MA, de Mello ES, Zilberstein B, Cecconelo I, Ribeiro U Jr. (2016) Carnoy’s solution increases the number of examined lymph nodes following gastrectomy for adenocarcinoma: a randomized trial. Gastric Cancer 19(1):136–142. doi: 10.1007/s10120-014-0443-2 (Epub 2014 Nov 20) CrossRefPubMedGoogle Scholar
  14. 14.
    Pereira MA, Dias AR, Faraj SF et al (2015) Carnoy’s solution is an adequate tissue fixative for routine surgical pathology, preserving cell morphology and molecular integrity. Histopathology 66(3):388–397. doi: 10.1111/his.12532 (Epub 2014 Nov 10) CrossRefPubMedGoogle Scholar
  15. 15.
    Ryan R, Gibbons D, Hyland JMP et al (2005) Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology 47:141–146CrossRefPubMedGoogle Scholar
  16. 16.
    Quirke P, Morris E (2007) Reporting colorectal cancer. Histopathology 50(103–11):2Google Scholar
  17. 17.
    Bateman AC, Jaynes E, Bateman AR (2009) Rectal cancer staging post neoadjuvant therapy—how should the changes be assessed? Histopathology 54:713–721CrossRefPubMedGoogle Scholar
  18. 18.
    Mandard AM, Dalibard F, Mandard JC et al (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 73:2680–2686CrossRefPubMedGoogle Scholar
  19. 19.
    Loughrey MB, Quirke P, Shepherd NA (2014) Dataset for colorectal cancer histopathology reports, 2nd edn. The Royal College of Pathologists, LondonGoogle Scholar
  20. 20.
    Rullier A, Laurent C, Capdepont M, Vendrely V, Bioulac-Sage P, Rullier E (2010) Impact of tumor response on survival after radiochemotherapy in locally advanced rectal carcinoma. Am J Surg Pathol 34:562–568CrossRefPubMedGoogle Scholar
  21. 21.
    Abdul-Jalil KI, Sheehan KM, Kehoe J, Cummins R et al (2014) The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer. Colorectal Dis 16(1):O16–O25. doi: 10.1111/codi.12439 CrossRefPubMedGoogle Scholar
  22. 22.
    Hiotis SP, Weber SM, Cohen AM et al (2002) Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg 194:131–135CrossRefPubMedGoogle Scholar
  23. 23.
    Bitterman DS, Salgado LR, Harvey G et al (2015) Predictors of complete response and disease recurrence following chemoradiation for rectal cancer. Front Oncol 5:1–9CrossRefGoogle Scholar
  24. 24.
    Ribeiro U Jr, Alves VA, de Souza PMSB et al (2000) Correlação das proteínas p53 e Ki67 com o prognóstico de pacientes com adenocarcinoma de reto distal. Rev bras Coloproct 20(4):248–256Google Scholar
  25. 25.
    Zorcolo L, Rosman AS, Restivo A et al (2012) Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol 19:2822–2832CrossRefPubMedGoogle Scholar
  26. 26.
    Kalady MF, de Campos-Lobato LF, Stocchi L et al (2009) Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg 250:582–589PubMedGoogle Scholar
  27. 27.
    Choi CH, Kim WD, Lee SJ, Park WY (2012) Clinical predictive factors of pathologic tumor response after preoperative chemoradiotherapy in rectal cancer. Radiat Oncol J 30:99–107CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Capirci C, Valentini V, Cionini L et al (2008) 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 72:99–107CrossRefPubMedGoogle Scholar
  29. 29.
    Dedemadi G, Wexner SD (2012) Complete response after neoadjuvant therapy in rectal cancer: to operate or not to operate? Dig Dis 30(2):109–117CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • M. A. Pereira
    • 1
  • A. R. Dias
    • 2
  • S. F. Faraj
    • 1
  • C. S. R. Nahas
    • 2
  • A. R. Imperiale
    • 2
  • C. F. S. Marques
    • 2
  • G. C. Cotti
    • 2
  • B. C. Azevedo
    • 2
  • S. C. Nahas
    • 2
  • E. S. de Mello
    • 1
  • U. RibeiroJr.
    • 2
  1. 1.Department of Pathology, Cancer InstituteUniversity of Sao PauloSão PauloBrazil
  2. 2.Department of Gastroenterology, Cancer InstituteUniversity of Sao PauloSão PauloBrazil

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