Results of Preoperative Concurrent Chemoradiotherapy for the Treatment of Rectal Cancer

Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

직장암의 수술 전 동시적 항암화학방사선치료 결과

목 적: 직장암에서 수술 전 동시적 항암화학방사선요법을 시행한 환자를 대상으로 항문 괄약근 보존율, 생존율, 예후인자 등을 알아보고자 하였다. 대상 및 방법: 1999년 1월부터 2007년 6월까지 직장암 환자로 진단되어 수술 전 동시적 항암화학방사선요법을 시행한 환자는 모두 150명이었다. 이 중 진단시 원격전이가 없고 재발암이 아니며 본원에서 근치적 수술을 받은 환자 중 계획된 방사선치료를 완료한 총 82명의 환자를 대상으로 하였다 방사선치료는 일일 $1.8{\sim}2\;Gy$씩, 주 5회 $41.4{\sim}46\;Gy$ (중앙값 44 Gy)를 전 골반에 조사한 후 원발부위 및 고위험 부위에 총 방사선량이 $43.2\;Gy{\sim}54\;Gy$(중앙값 50.4 Gy)까지 추가 조사하였다. 항암화학요법은 66명(80.5%)에서 5-fluorouracil (5-FU), leucovorin, cisplatin을 정주하였고, 15명(19.5%)에서는 5-FU와 leucovorin만을 정주하여 방사선치료 기간 동안 4주 간격으로 2회 시행되었다. 수술은 동시적 항암화학방사선치료 종료 후 $3{\sim}45$주(중앙값 7주)가 경과되어 시행되었다. 수술 후 유지 항암화학요법은 총 38명(47.6%)에서 시행되었다. 결 과: 전체 환자의 항문 괄약근 보존율은 73.2%(60명)이었다. 이 중 종양의 최하 위치가 항문연으로부터 5 cm 미만인 환자 48명중 31명(64.6%)에서, 5 cm 이상인 환자 34명 중 29명(85.3%)에서 항문 괄약근을 보존할 수 있었다. 수술 후 병리적 완전관해율은 14.6% (12/82)였다. 전체 환자의 T병기 하강률은 42.7% (35/82)였고, N병기 하강률은 75.5% (37/49)였으며, 전체 병기 감소율은 67.1% (55/82)였다. 전체 환자의 추적 관찰 기간은 $11{\sim}107$ 개월로 중앙값은 38개월이었다. 전체 환자의 5년 생존율, 무병생존율 및 국소종용제어율은 각각 67.4%, 58.9%, 84.4%였다. 수술 후 병기별 5년 생존율은 0 (n=12), I (n=16), II (n=30), III (n=23)기에서 각각 100%, 59.1%, 78.6%, 36.9%이었고 IV 병기 1예는 43개월 현재 생존 중이다(p=0.02). 병기별 5년 무병생존율은 0, I, II, III, IV 기에서 각각 77.8%, 63.6%, 58.9%, 51.1%, 0%였다(p<0.001). 병기별 5년 국소종양제어율은 0, I, II, III기 에서 각각 88.9%, 93.8%, 91.1%, 68.2%였고 IV병기 1예는 43개월 현재 국소재발 없이 생존 중이다(p=0.01). 생존율에 영향을 미치는 예후인자를 분석하기 위하여 연령(${\geq}55$세 VS. >55세), 임상적 병기(I+II vs, III), 방사선치료 종료 후 수술까지의 경과기간(${\leq}6$주 vs. >6주), 수술방법 (항문괄약근보존술 vs. 비보존술), 병리학적 T병기, 병리학적 N 병기, 병리학적 전체병기(0 vs. I+II vs. III+IV), 병리학적 완전관해여부 등 총 8개의 다변량 분석상, 연령과 병리학적 N병기는 전체 생존율에, 병리학적 전체 병기는 무병생존율에, 병리학적 N병기는 국소종양제어율에 각각 유의하였다. 전체 환자 중 재발한 환자는 모두 25명으로 국소재발 10명, 원격전이 13명, 국소 및 원격전이가 동시에 있던 환자 2명이었다 항암화학 방사선치료 중 등급 3 이상의 혈액학적 독성은 백혈구 감소가 2명이었고, 등급 3의 피부반응이 1명이었다. 수술 후 60일 이내의 입원을 요할 정도의 합병증으로는 총 11명으로 문합부 누출 5명, 골반부 농양이 2명, 그외 4명 등이었다. 결 론: 직장암에서 수술 전 동시적 항암화학방사선요법으로 병기 하강 및 항문 괄약근 보존에 유용한 결과를 얻었고, 수술 전 항암화학방사선요법으로 인한 독성은 미미하였다. 병리학적 N병기가 생존율과 국소종양제어율에 유의한 예후 인자로 나타나 이들에 대한 수술 후 보조적 요법이 더욱 강화될 필요가 있다고 생각된다.