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Complete Pathologic Response Following Preoperative Chemoradiation Therapy for Middle to Lower Rectal Cancer Is Not a Prognostic Factor for a Better Outcome

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Diseases of the Colon & Rectum

PURPOSE

The aim of this study was to evaluate factors associated with pathologic tumor response following preoperative chemoradiation therapy, and the prognostic impact of pathologic response on overall and disease-free survival.

METHODS

Between 1994 and 2002, 132 patients underwent chemoradiation therapy followed by surgery for middle to lower rectal cancer. After excluding 26 cases (metastatic cancer, n = 13; nonradical surgery, n = 6; local excision procedure, n = 4; non-5-fluorouracil-based chemotherapy, n = 2; incomplete data on preoperative chemoradiation therapy regimen used, n = 1), the remaining 106 patients were included in the study. Variables considered were the following: age, gender, tumor location, pretreatment T and N stage, modality of 5-fluorouracil administration, total radiotherapy dose delivered, chemoradiation therapy regimen used (Regimen A: chemotherapy (bolus of 5-fluorouracil and leucovorin, days 1–5 and 29–33) + radiotherapy (45 Gy/25 F/1.8 Gy/F); Regimen B: chemotherapy (5-fluorouracil continuous venous infusion ± weekly bolus of carboplatin or oxaliplatin) + radiotherapy (50.4 Gy/28 F/1.8 Gy/F)), time interval between completion of chemoradiation therapy and surgery, postoperative chemotherapy administration, surgical procedures, pT, pN, and pTNM stage, and response to chemoradiation therapy defined as tumor regression grade, scored from 1 (no tumor on surgical specimen) to 5 (absence of regressive changes). Statistical analysis was performed by means of logistic regression analysis (Cox’s model for overall and disease-free survival).

RESULTS

Median age of the 106 patients was 60 (range, 31–79) years and the male:female ratio, 66:40. Median distance of tumor from the anal verge was 6 (range, 1–11) cm. Pretreatment TNM stage, available in 104 patients, was cT3–T4N0, n = 41; cT2N1, n = 9; cT3N1, n = 39; and cT4N1, n = 17. The median radiotherapy dose delivered was 50.4 (range, 40–56) Gy; 58 patients received 5-fluorouracil by continuous venous infusion, and carboplatin with oxaliplatin was added to the chemotherapy schedule in 71 cases. Patients were given Regimen A in 47 cases and Regimen B in 59. The median interval between chemoradiation therapy and surgery was 42.5 (range, 19–136) days, and 94 patients underwent a sphincter-saving procedure. Tumor regression grade, available in 104 cases, was 1, n = 19; 2, n = 18; 3, n = 15; 4, n = 13; and 5, n = 39. At a median follow-up of 42 (range, 1–110) months, 11 patients had died, and 95 were alive. None of the patients had local recurrences, but 13 had distant recurrences. At logistic regression analysis, the chemoradiation therapy regimen used was the only independent predictor of tumor response following preoperative chemoradiation therapy (odds ratio = 0.29, 95% confidence interval = 0.13–0.67, P = 0.003). At Cox’s regression analysis, pretreatment T stage was the only independent prognostic factor for both disease-free survival (relative risk = 7.13, 95% confidence interval = 2.3–21.8, P = 0.001) and overall survival (relative risk = 4.83, 95% confidence interval = 1.1–19.9, P = 0.029).

CONCLUSIONS

Tumor response following preoperative chemoradiation therapy is mainly related to the preoperative regimen used. For patients receiving preoperative chemoradiation therapy, pretreatment T stage, but not tumor response to preoperative chemoradiation therapy, is prognostic for outcome (both disease-free and overall survival).

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ACKNOWLEDGMENT

The authors thank Ms. Sara Pearcey for her assistance with the English language.

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Authors and Affiliations

  1. Dipartimento di Scienze Oncologiche e Chirurgiche, Padova University, Padova, Italy

    Salvatore Pucciarelli M.D., Paola Toppan M.D., Valentina Russo M.D., Emanuele Urso M.D., Filippo Marino M.D., Alessandro Ambrosi Ph.D. & Mario Lise M.D.

  2. Divisione di Radioterapia, Azienda Ospedaliera di Padova, Padova, Italy

    Maria Luisa Friso M.D.

  3. Divisione di Oncologia Medica, Azienda Ospedaliera di Padova, Padova, Italy

    Lara Pasetto M.D.

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  1. Salvatore Pucciarelli M.D.
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  2. Paola Toppan M.D.
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Correspondence to Salvatore Pucciarelli M.D..

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Pucciarelli, S., Toppan, P., Friso, M. 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 47, 1798–1807 (2004). https://doi.org/10.1007/s10350-004-0681-1

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