Int J Colorectal Dis (2007) 22: 7–13 DOI 10.1007/s00384-006-0092-y ORIGINAL ARTICLE Enrico Benzoni Giovanni Terrosu Donatella Intersimone Elisa Milan Germana Chiaulon Vittorio Bresadola Cosimo Sacco Elisa Sattin Fabrizio Bresadola Claudio Avellini Accepted: 23 December 2005 Published online: 15 March 2006 # Springer-Verlag 2006 Instrumental clinical restaging, pathological evaluation, and tumor regression grading: how to assess the response to neoadjuvant chemoradiotherapy for rectal cancer Abstract Introduction: The object of neoadjuvant chemoradiotherapy regimens is a downstaging or down- sizing of advanced rectal tumor to increase the rate of curative resection and reduce loco-regional failure. A reliable method of assessing response to adjuvant therapies is required to help standardize the assessments of new multimodality therapies. The purpose of this study was to evaluate the role played by tumor regression grading on the evaluation of patho- logical response to chemoradiotherapy, compared with both the predicting value of the clinical response to neo- adjuvant therapy and pathologic re- sponse evaluation. Methods: From 1994 to 2003, 58 patients with a pri- mary diagnosis of rectal cancer were studied at our department and enrolled in a single center, not randomized study based on 5-week sessions of radiotherapy associated with a 30-day 5-fluorouracil (FU) infusion, followed by surgical resection. Instru- mental restaging and routine histolog- ical examination, including tumor regression grading, were performed to asses the response to neoadjuvant therapy. Results: The cCR rate corresponds to pCR rate, while a 3.5% of cPR and a 3.4% of cSD corre- sponded to a pPD. cPR and cSD show a PPV of 92.8% and 90.9% respec- tively, while cPD NPV is 20%. No case was found with no regression (grade 0). Tumor regression was defined grade 1 in 24.5% of cases, grade 2 was found in 58.5% of cases, 7.5% were grade 3, and 9.5% showed complete regression (grade 4). Patho- logic response resulted to be asso- ciated with regression grade (p=0.006). Tumor regression grading is an independent variable for pT (p=0.0002), pN status (p=0.00004), pathologic staging (p=0.000001) and local recurrence (p=0.003). Conclusion: Our results lead us to consider only pathologic evaluation to determine the response to neoadjuvant treatment: the application of tumor regression grading on the specimens obtained after combined neoadjuvant chemoradiotherapy and surgery is useful to plan a better therapeutic strategy on the ground of a quantita- tive evaluation of the response to neoadjuvant treatment; it shows it is an important comparable pathological feature, useful in comparing different protocols’ results and differences be- tween patient’ s response as well as prognostic factors. Keywords Tumor regression grading . Restaging . Pathologic response . Rectal cancer . Neoadjuvant therapy Abbreviations CRT: chemoradiotherapy . cCR or pCR: clinical or pathological complete response . cPR or pPR: clinical or pathological partial response . cSD or pSD: clinical of pathological stationary disease . cPD or pPD: clinical or pathological progressive disease . CT: computerized tomography . ERUS: endorectal ultrasound . MR: magnetic resonance . NPV : negative predictive value . PPV : positive predictive value . TRG: tumor regression grading E. Benzoni . G. Terrosu . E. Milan . V. Bresadola . E. Sattin . F. Bresadola Department of Surgery, University of Udine School of Medicine, Udine, Italy D. Intersimone . C. Avellini Department of Pathology, University of Udine School of Medicine, Udine, Italy G. Chiaulon Department of Radiotherapy, “S. Maria della Misericordia” Hospital of Udine, Udine, Italy C. Sacco Department of Oncology, University Hospital of Udine, Udine, Italy E. Benzoni (*) Università degli Studi di Udine, Policlinico Universitario a Gestione Diretta, Dipartimento di Scienze Chirurgiche, Clinica di Chirurgia Generale, P.le S. Maria della Misericordia, 33100 Udine, Italy e-mail: enricobenzoni@yahoo.it Tel.: +390432559566 Fax: +390432559564