子宮頸癌術後放射線治療病人組織病理學預後因子之多變數分析

中文摘要 研究背景: 子宮頸癌截至目前仍然是台灣婦女發生率最高且最常見的癌症之一. 雖然經過適當治療後其死亡率可大幅控制, 但有某些早期子宮頸癌雖經外科手術並輔以術後放射線治療, 其預後仍比預期的更差. 或許除了臨床分期以外可能還有某些因素存在, 而且確實對早期子宮頸癌的預後有一定程度的影響. 本文從許多作過根除性子宮切除術 (包括全子宮切除術) 的標本中檢視其詳細病理報告, 並推估究竟那些組織病理學因子對預測早期子宮頸癌的預後扮演重要的角色. 材料與方法: 彰化基督教醫院南郭醫療中心放射腫瘤科自民國七十四年十二月一日迄民國八十年十二月三十一日共計有 126 例經病理診斷證實之第一與第二期子宮頸癌病人接受過根治性子宮切除術合併骨盆腔淋巴腺摘除術 ( 包括全子宮切除術在內 ) 與術後輔助性放射線治療. 放射線治療主要來自術後病理檢查發現有淋巴腺轉移, 手術邊緣有癌細胞侵犯, 淋巴血管浸潤, 原發腫瘤大於或等於 3.0 公分, 子宮旁組織侵犯,子宮 體擴散或僅作單純子宮切除術等因素. 體外放射線劑量通常全骨盆腔接受39.6 至 61.2 Gy 之腫瘤劑量, 另外在陰道縫合緣再追加腔內近接治療. 所有接受過完整放射線治療的病患至少皆有九年之追蹤期 ( ≧ 108 個月 ). 與預後相關之病理組織學參數如病理學分類, 腫瘤分化程度, 腫瘤縱深徑, 淋巴血管間隙侵犯, 子宮體擴散, 子宮旁組織侵犯, 陰道侵犯及骨盆淋巴腺轉移等皆經搜集分類並以統計軟體作單變數與多變數分析. 研究結果: 所有的 126例個案皆經過審慎的評估, 分析與追蹤一直 到研究結束(民國九十年六月). 到目前已有半數病人 ( 63 例) 死亡, 中值追蹤期為 113個月( 範圍: 8─256 月). 存活期間的計算是由病 理診斷日算起直到最後追蹤日期或死亡日期. 依據外科分期的結果, IB, IIA, IIB 各期之估計五年與十年存活率分別為 65%, 75%, 62% 與 59%, 49%, 53% ( p >0.05). 單變數分析結果指出, 骨盆腔淋巴腺轉移, 組織病理學分類, 腫瘤大小與子宮體侵犯四個變項對存活率有顯著性的影響 ( p <0.05). 經過 Cox regression model 進行多變數分析以後, 僅有組織病理學分類與骨盆腔淋巴腺轉移二變項被鑑定為獨立且顯著性強之預後因子 ( p <0.005 ). 討論: 本篇研究報告經 Cox’s model 分析後找出組織病理學分類與 骨盆腔淋巴腺轉移為兩個獨立且意義顯著之預後變數. 對於骨盆淋 巴腺轉移若數目在兩個以上且病理分類屬非鱗狀上皮細胞癌 (特別 是腺狀細胞癌) 時, 其預後型態可能最差. 此一針對子宮頸癌各種術後組織病理學預後因子所作的回顧性分析調查, 旨在進一步探討早期能以外科切除的子宮頸癌除了臨床分期外, 是否還可區分其他較顯著的危險因子俾能更準確地預測疾病的預後, 並作為改變治療模式的新指標. 關鍵字: 子宮頸癌, 預後因子, 多變數分析

ABSTRACT Background : Cervical cancer is by now still keeping its high rank incidence as one of the most popular cancers of women in Taiwan. Although its mortality rate is modest if treated properly, however, some early stage cancers of the uterine cervix still behave out of our expectation despite surgery and post-operative irradiation. Probably several factors exist which indeed affect the ultimate prognosis of early stage cervical cancer other than clinical staging. We have inves- tigated detailed pathological reports from hysterectomy specimen and evaluate whether some histopathological factors might really play major roles in predicting the prognosis of early stage carcinoma of the uterine cervix. Materials and Methods: Between 1st, Dec. 1985 and 31, Dec. 1991, 126 patients with pathology-proven stages I and II carcinoma of the uterine cervix were treated by radical hysterectomy and pelvic lymphadenectomy ( some of them undergone ATH ) followed with post-operative irradiation at Department of Radiation Oncology, Chang-hua Christian Hospital. The indications for radiotherapy were based on pathologic findings including lymph node metastasis, positive surgical margins, lymphvascular permeation, primary tumor size ≧3.0 cm, parametrial involvement, corpus invasion, previous inadequate surgery ( ATH ) or more than one combination of the above. Patients usually received external beam irradiation 39.6 Gy to 61.2 Gy to the whole pelvis, and the vaginal cuff were boosted by intravaginal brachytherapy. All patients who received complete course of radiotherapy had minimal follow-up period of at least nine years (≧108 months). The prognosis-related histologic parameters including histologic subtypes, tumor grade, longitudinal tumor dimension, lymph-vascular space invasion, corpus invasion, para- metrial extension, vaginal invasion and pelvic lymph node (PLN ) metastases were collected and evaluated with univariate and multivariate analysis. Results : All the 126 cases were evaluated, analyzed and followed until closure of this study( Jun. 2001). Half ( 63 ) of all the cases died. The median follow-up duration was 113 months ( range: 8 —256 ). The survival duration was calculated from time of histologic diagnosis to the time of last follow-up or death. The estimated 5- and 10-year survival rate of surgical stages IB, IIA and IIB were 65%, 75%, 62% and 59%, 49%, 53% respectively ( p > 0.05). Univariate analysis revealed that PLN metastases, histologic subtype, tumor size and corpus invasion were significant in survival ( p <0.05 ). Among these variables, we found that histologic subtype and PLN metastases were identified as the most independent and significant prognostic factors ( p <0.005) by multivariate analysis using Cox regression model. Discussions : In the current study, we found that histologic subtype and PLN metastases were recognized as two independent and signi- ficant prognostic variables by Cox’s model. For number of metasta- tic nodes more than two and non-SCC from pathologic classification ( especially adenocarcinoma ), the prognosis might be the worst. This retrograde analytical survey of various postoperative histo- pathological prognostic factors indicates a need for subdivision by more significant risk factors which could predict the outcome of surgically resectable early-stage cervical cancer more precisely than clinical staging and also serves as a new indicator for changing treatment modality. Key words : Uterine cervix, Prognostic factors, Multivariate analysis