Surgery Plus Chemo Versus Chemoradiotherapy Followed by Surgery Plus Chemo for Locally Recurrent Rectal Cancer

Inclusion Criteria:

1. Histopathologically proven adenocarcinoma or adenosquamous carcinoma on the resectedspecimen of the initial rectal cancer or endoscopic biopsy from the initial rectalcancer.

2. The main tumor location of the initial rectal cancer is upper, middle or lower rectum,or anal canal.

3. Either of the following treatments was performed for the initial rectal cancer, andclassified as R0/1 or ER (Endoscopical R)0/1 on pathological diagnosis. i) Surgical resection (including local resection, with or without lymph nodedissection). ii) Endoscopic resection.

4. Patients with distant metastasis during or after treatment for the initial rectalcancer, and radical surgical resection or radical radiotherapy performed more than 168days before registration is eligible.

5. Recurrent rectal cancer diagnosed by any of the following modalities after treatmentfor the initial rectal cancer. i) The recurrent lesion is pathologically diagnosed. ii) Diagnosed as local recurrenceby more than two modalities among contrast-enhanced CT, contrast-enhanced MRI, orpositron emission computed tomography (PET). iii) Chronological progression of the lesion seen on more than one modality amongcontrast-enhanced CT, MRI, or PET.

6. The main tumor location is within pelvis as seen on contrast-enhanced CT and MRI ifrecurrent lesion is multiple, or recurrent lesions spread outside of pelviscontinuously.

7. LRRC is diagnosed with no following condition. i) Judged as resectable endoscopically.ii) Depth of invasion within the muscularis propria as seen on contrast-enhanced CT,MRI, or PET in case of recurrence inside the intestine iii) Solitary ovarianmetastasis. iv) Recurrence of the common iliac lymph node alone.

8. LRRC is diagnosed as resectable, and all the following conditions must be fulfilled: i) No distant metastasis on contrast-enhanced CT (cM0). ii) Estimated circumferentialresection margin ＞0 mm. iii) Leg amputation not required. iv) Preservation of thefirst sacral nerve possible.

9. No prior surgery for recurrent rectal cancer.

10. No prior pelvic irradiation for any malignancies.

11. A patient who has received systemic chemotherapy for any malignancies and the finaldose was administered more than 14 days ago.

12. Age at registration is 20 to 80 years old.

13. Eastern Cooperative Oncology Group (ECOG) performance status is 0 or 1.

14. Measurable lesion is not mandatory.

15. Adequate oral intake.

16. Sufficient organ function. i) Neutrophil count >= 1,500/mm3 ii) Hemoglobin >= 9.0 g/dLiii) Platelet count >= 100,000/mm3 iv) Total Bilirubin =< 2.0 mg/dL v) Aspartateaminotransferase (AST) =< 100 U/L vi) Alanine Aminotransferase (ALT) =< 100 U/L vii)Cr =< 1.5 mg/dL

17. Open surgery or laparoscopic surgery is planned.

18. Written informed consent is obtained.

Exclusion Criteria:

1. Synchronous or metachronous (within 5 years) malignancies except cancer with 5-yearrelative survival rate of 95% or more such as carcinoma in situ, intramucosal tumor,or early stage cancers.

2. Infections requiring systemic treatment.

3. Body temperature higher than 38 degrees Celsius at registration.

4. Pregnant female, female within 28 days post-parturition, or lactating mother. Men withpartners planning conception in the near future.

5. Severe psychological disease.

6. Continuous systemic corticosteroid or immunosuppressant treatment.

7. Uncontrollable diabetes mellitus.

8. Uncontrollable hypertension.

9. Unstable angina pectoris, or history of myocardial infarction within 6 months.

10. Uncontrollable valvular disease, dilated cardiomyopathy, or hypertrophiccardiomyopathy.

11. Positive serum Hepatitis B (HB)s antigen or serum Hepatitis C Virus (HCV) antibody.

12. Positive serum HIV antibody.

13. Interstitial pneumonia, pulmonary fibrosis, or severe emphysema on chest CT.