Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum

R. S. Chari, Douglas Tyler, M. S. Anscher, L. Russell, B. M. Clary, J. Hathorn, H. F. Seigler, E. M. Copeland, M. M. Urist

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Abstract

Objective: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease tree survival and pelvic recurrence rates were examined, and compared with a concurrent control group. Summary Background Data: The optimal treatment of large rectal carcinomas remains controversial: current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. Methods: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5 week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy proven lesions >3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease free survival, and pelvic recurrence rates. Results: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens of the 30 patients with evidence of residual disease, 4 had positive lymph nodes in follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (<5%). Cox- Mantel analysis of Kaplan Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p =0.031) for protocol versus control patients. Conclusions: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.

Original languageEnglish (US)
Pages (from-to)778-787
Number of pages10
JournalAnnals of Surgery
Volume221
Issue number6
StatePublished - 1995
Externally publishedYes

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Rectum
Adenocarcinoma
Radiation
Drug Therapy
Therapeutics
Recurrence
Neoplasm Metastasis
Sigmoidoscopy
Survival
Disease-Free Survival
Lymph Nodes
Control Groups
Kaplan-Meier Estimate
Fluorouracil
Cisplatin
Tomography

ASJC Scopus subject areas

  • Surgery

Cite this

Chari, R. S., Tyler, D., Anscher, M. S., Russell, L., Clary, B. M., Hathorn, J., ... Urist, M. M. (1995). Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Annals of Surgery, 221(6), 778-787.

Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. / Chari, R. S.; Tyler, Douglas; Anscher, M. S.; Russell, L.; Clary, B. M.; Hathorn, J.; Seigler, H. F.; Copeland, E. M.; Urist, M. M.

In: Annals of Surgery, Vol. 221, No. 6, 1995, p. 778-787.

Research output: Contribution to journalArticle

Chari, RS, Tyler, D, Anscher, MS, Russell, L, Clary, BM, Hathorn, J, Seigler, HF, Copeland, EM & Urist, MM 1995, 'Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum', Annals of Surgery, vol. 221, no. 6, pp. 778-787.
Chari RS, Tyler D, Anscher MS, Russell L, Clary BM, Hathorn J et al. Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Annals of Surgery. 1995;221(6):778-787.
Chari, R. S. ; Tyler, Douglas ; Anscher, M. S. ; Russell, L. ; Clary, B. M. ; Hathorn, J. ; Seigler, H. F. ; Copeland, E. M. ; Urist, M. M. / Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. In: Annals of Surgery. 1995 ; Vol. 221, No. 6. pp. 778-787.
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title = "Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum",
abstract = "Objective: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease tree survival and pelvic recurrence rates were examined, and compared with a concurrent control group. Summary Background Data: The optimal treatment of large rectal carcinomas remains controversial: current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. Methods: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5 week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy proven lesions >3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease free survival, and pelvic recurrence rates. Results: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51{\%}) were determined to have complete clinical response. At the time of resection, 21 patients (49{\%}) had gross disease, 9 (22{\%}) patients had only residual microscopic disease, and 11 (27{\%}) had sterile specimens of the 30 patients with evidence of residual disease, 4 had positive lymph nodes in follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (<5{\%}). Cox- Mantel analysis of Kaplan Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p =0.031) for protocol versus control patients. Conclusions: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27{\%} incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.",
author = "Chari, {R. S.} and Douglas Tyler and Anscher, {M. S.} and L. Russell and Clary, {B. M.} and J. Hathorn and Seigler, {H. F.} and Copeland, {E. M.} and Urist, {M. M.}",
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TY - JOUR

T1 - Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum

AU - Chari, R. S.

AU - Tyler, Douglas

AU - Anscher, M. S.

AU - Russell, L.

AU - Clary, B. M.

AU - Hathorn, J.

AU - Seigler, H. F.

AU - Copeland, E. M.

AU - Urist, M. M.

PY - 1995

Y1 - 1995

N2 - Objective: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease tree survival and pelvic recurrence rates were examined, and compared with a concurrent control group. Summary Background Data: The optimal treatment of large rectal carcinomas remains controversial: current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. Methods: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5 week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy proven lesions >3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease free survival, and pelvic recurrence rates. Results: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens of the 30 patients with evidence of residual disease, 4 had positive lymph nodes in follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (<5%). Cox- Mantel analysis of Kaplan Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p =0.031) for protocol versus control patients. Conclusions: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.

AB - Objective: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease tree survival and pelvic recurrence rates were examined, and compared with a concurrent control group. Summary Background Data: The optimal treatment of large rectal carcinomas remains controversial: current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. Methods: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5 week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy proven lesions >3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease free survival, and pelvic recurrence rates. Results: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens of the 30 patients with evidence of residual disease, 4 had positive lymph nodes in follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (<5%). Cox- Mantel analysis of Kaplan Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p =0.031) for protocol versus control patients. Conclusions: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.

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