Preliminary Results of Pelvic Autonomic Nerve-preserving Surgery Combined with Intraoperative and Postoperative Radiation Therapy for Patients with Low Rectal Cancer

Jpn J Clin Oncol1999;29(9)429-433 Preliminary Results of Pelvic Autonomic Nerve-preserving Surgery Combined with Intraoperative and Postoperative Radiation Therapy for Patients with Low Rectal Cancer Satoshi Ishikura1, Takashi Ogino1, Masato On02, Tatsuo Arai 2, Masanori Sugit02, Wakako Shimizu 1, Mitsuhiko Kawashima1, Michiko ImaP, Yoshinori Ito1 and Hiroshi Ikeda1 1Radiation Oncology Division and 2Gastrointestinal Surgical Oncology Division, National Cancer Center Hospital East, Kashiwa, Japan Background: /n Japan, latera/lymphadenectomy was widely performed for patients with stage II-III rectal tumors because it was thought to contribute to good local control, but the pelvic autonomic nerves were thus sacrificed. Although autonomic nerve-sparing surgery with lateral lymph nodedissection has beentried from around 1987,the type of nervesparing variedandthe indications were not established. To examine the possibility of expanding the indications for total pelvicautonomic nervepreservation for patients withlowrectal cancer, we conducted a pilotstudy. Methods: Between 1993and 1997, a total of 50 patients with low rectal cancerunderwent pelvic autonomic nerve preservation with lateral lymphadenectomy of both sides and intraoperative radiation therapy followed by postoperative radiation therapy. Results: The median follow-up period for surviving patients was 41 months. The 3-year local control rates for all patients,'with stage I-II and stage III tumors were 880/0 (95% confidence interval, 78-97%), 97% (90-100%) and73% (52-94%), respectively. The siteof localrecurrences was not near or within the preserved plexus. Conclusions: The preliminary results showed good local control rate for patients with stage I-II tumors. For patients with stage III tumors, the local control rate was unsatisfactory, but nerve sparing was notthe causeof localrecurrence. Further investigation of function-preserving surgery without decreasing curability is needed. Keywords: lowrectal cancer-pelvic autonomic nerve-preserving surgery-intraoperative andpostoperative radiotherapy INTRODUCTION In patients with advanced rectal cancer, it is difficult to preserve urinary and sexual function with the conventional surgical procedures which resect the mesorectum bluntly and blindly. In addition, the reported local recurrence rate is rather poor, -20-30% (1-5). More recently, the local recurrence rate has declined to 5-8% owing to the introduction of the total mesorectal excision (TME) technique with/without adjuvant therapy (2,6,7). In Japan, lateral lymph node dissection was thought to be ReceivedMarch 5, 1999;accepted May 31, 1999 For reprints and all correspondence: Satoshi Ishikura, RadiationOncology Division, National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa 277-8577,Japan. E-mail: Abbreviations: TME,total mesorectal excision; PANP, pelvic autonomic nerve preservation; CEA, carcinoembryonic antigen; CT, computed tomography; MR!, magnetic resonance imaging; IORT, intraoperative radiation therapy; PORT, postoperative radiation therapy;CTV, clinicaltarget volume; PTV, planning target volume; BED,biologically effective dose necessary to obtain good local control and pelvic autonomic nerves were sacrificed for patients with advanced-stage rectal cancer (8). Pelvic autonomic nerve preservation (PANP) surgery with lateral lymph node dissection has been tried from around 1987; the type of PANP varied and the indications were not established. In 1993, it was not commonly accepted to perform total PANP for patients who had a potential for stage IT or ill rectal cancer. We therefore started this study to examine the possibility of expanding the indications for total PANP. We report here the preliminary results. MATERIALS AND METHODS PATIENT POPULATION AND TUMOR CHARACTERISTICS Between 1993 and 1997, 50 patients with low rectal cancer, at or below the peritoneal reflection, were enrolled in this pilot study. The patient selection criteria were (l) biopsy-proven low rectal cancer, (2) a tumor without direct invasion to bilateral pelvic nerve plexuses on preoperative evaluation and at surgery, (3) a tumor without bilateral lateral lymph node involvement con© 1999Foundation for Promotion of Cancer Research 430 PANP surgery with IORT in rectal cancer firmed histologically at surgery, (4) without distant metastasis (except for liver metastasis for which complete resection is possible) and (5) written informed consent. During this period, 66 patients were considered eligible preoperatively, but 16 patients were revealed to be ineligible at surgery and excluded from the study. The pretreatment evaluation included a complete history, physical examination, colonoscopy, complete blood count, liver function profile, creatinine, serum carcinoembryonic antigen (CEA), chest X-ray, ultrasound of the liver, computed tomography (CT) scan of the abdomen and the pelvis, magnetic resonance imaging (MRI) of the pelvis and endorectal ultrasound . The patient and tumor characteristics are given in Table I . SURGERY The operative procedures included low anterior resection in 26 patients and abdominoperineal resection in 24 and both were performed with combining the Tl\1E technique and lateral lymph node dissection. All patients underwent total PANP, i.e. the hypogastric nerve and bilateral pelvic nerve plexuses were preserved, with lateral lymphadenectomy on both sides. Table 1. Patient and tumor characteristics Characteristic No. Age (median) 40-73 (57) years Gender Male 34 Female 16 Type of surgery* APR 24 LAR 26 Tumor classification Figure 1. The cone for intraoperative radiation therapy (lORn is fitted to the pelvicnerveplexus underdirect vision. RADIATION THERAPY The purpose of radiation therapy in this study was for prophylactic treatment only to the tissue near and within the preserved pelvic nerve plexuses which were not dissected and might have microscopic residual tumor. This was different from common postoperative radiation therapy (PORT) for tumor bed and regional lymph nodes. The purpose of combination of intraoperative radiation therapy (IORT) with PORT is to reduce the radiation dose to the small intestine while maintaining the intensity of radiation at the target. This leads to a decrease in the rate of late radiation toxicities, such as diarrhea and intestinal obstruction, which is a major problem in performing common PORT using external beam radiotherapy alone. The small intestine does not receive any radiation using IORT. T1 T2 II T3 37 T4 Pathological stage 12 II 17 III 19 IV 2 INTRAOPERATIVE RADIATION THERAPY All patients received IORT to the bilateral preserved pelvic nerve plexuses separately. The size of the cone used was 4 em in diameter and the electron energy used was 5 MeV. The radiation doses delivered were 15 Gy. The clinical target volume (CTV) included the pelvic nerve plexuses excluding the ureters and the planning target volume (PTV) wa (...truncated)