術前化學治療改善侵犯性泌尿上皮癌患者整體存活率之療效

Neoadjuvant chemotherapy improved survival rate in advanced urothelial carcinoma

蔡嘉駿(Chia-Chun Tsai)

指導教授 ： 黃俊雄

高雄醫學大學/醫學院/醫學研究所/碩士(2011年)

https://doi.org/10.6832/KMU.2011.00030

摘要

研究背景與目的 傳統對於侵犯性泌尿上皮癌患者，以往均採用根除手術來進行治療，術後再依照病患情形進行術後輔助性全身化學治療。目前已有研究提出對於局部侵犯性膀胱癌患者，使用術前化學治療合併根除手術會有較佳的預後。但對於侵犯性泌尿上皮癌患者，全身性化學治療應術前使用或術後使用，目前仍未有定論，而之前研究中有包括上泌尿道泌尿上皮癌患者的報告更是少之又少，並且目前仍缺乏台灣地區的報告。因此本研究試著探討對於台灣地區侵犯性泌尿上皮癌患者，包括上泌尿道泌尿上皮癌與膀胱癌，術前化學治療是否對於整體預後有所幫助。
研究方法 本研究採病歷回溯的方式，從民國91年3月到民國100年3月，收集於高雄醫學大學附設醫院、高雄市立大同醫院與高雄市立小港醫院接受根除性手術治療與全身性化學治療的侵犯性泌尿上皮癌患者進行整理分析。將病人分為兩組，第一組接受至少三個療程的術前全身性化學治療再進行根除手術；第二組則先接受根除手術後合併術後全身性化學治療。二組病人的完整病史、病理資料、治療反應、手術併發症與化療毒性均詳加記錄及比較。關於無病變存活期與整體存活期則使用Kaplan-Meier method來加以比較，p值小於0.05表示有統計顯著意義。
研究結果 本研究一共收集了101位侵犯性泌尿上皮癌患者進行整理分析，當中因部份治療過程及資料不完整，故將其中37位患者加以排除。結果共64位侵犯性泌尿上皮癌患者納入本研究，其中有30位(47%)患者進行術前化學治療合併根除手術，而另有34位(53%)患者先進行根除手術再合併術後全身性化學治療。在接受術前化學治療合併根除手術這組，術後腫瘤病理期別（p＝0.002）、惡性度（p＝0.018）與周邊血管淋巴侵犯（p＝0.034）均達到有顯著意義的下降，而且更可發現有26.7%的病人達到完全緩解(於根除手術後之檢體找不到腫瘤)。至於化療副作用與手術併發症的發生率，兩組比較起來並無顯著的差異，除了根除手術合併術後化學治療組似乎有較多的院內感染之比率(p＝0.042)。而術前化學治療合併根除手術這組對於無病變存活期(p＝0.002)與整體存活期(p＝0.018)，也都有明顯的較佳表現。
研究結論 在此研究中我們發現，在不增加手術併發症與化療副作用的情況之下，使用術前化學治療合併根除手術來治療侵犯性泌尿上皮癌患者，不僅能達到腫瘤期別的下降，對於無病變存活期與整體存活期也有著明顯的改善。

關鍵字

術前化學治療 ； 侵犯性泌尿上皮癌 ； 存活率

並列摘要

Objectives: Traditionally, radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy is suggested for patients with advanced urothelial carcinoma (AUC). At present, some contemporary analyses indicate that systemic neoadjuvant chemotherapy (NC) has significant improvement in survival rate of patients with locally advanced bladder cancer. However, there are no well established criteria that would help to determine which treatment – NC or AC – should be administered to patients with AUC. Furthermore, few studies about the impact of NC on AUC in upper urinary tract (UUT) were reported and no study was performed in Taiwan, where has higher incidence rate of urothelial carcinoma than the world wide. Hence, the present study aims to investigate whether application of NC improves the length of survival period in patients with AUC (including UUT and bladder) in Taiwanese population.
Methods: Reviewing chart data from patients with AUC underwent radical surgery (RS) as well as systemic chemotherapy at our institutions between March 2002 and March 2011. They were stratified into two groups. The first group received at least 3 cycles of systemic NC prior to RS. The second group first had RS after which systemic AC was administered. The clinical response, surgical complications and adverse effects of chemotherapy between the two groups were analyzed and compared. Progression-free survival (PFS) as well as overall survival (OS) of patients were calculated according to the Kaplan-Meier method. p < 0.05 was considered statistically significant.
Results: We enrolled 101 patients over an 9-year period and 37 of whom were found to be ineligible with incomplete therapeutic course or inadequate data. 30 were received NC prior to RS and 34 were received RS followed by systemic AC. There was a significant reduction of pathologic stage (p =0.002), grade (p =0.018) and lymphovascular invasion (p =0.047) in group who received initial NC compared with the other group. Furthermore, 26.7 % patient with NC followed by RC had complete remission in the surgical specimen. There were no significant differences in surgical complications and adverse effects of chemotherapy between the two groups, except nosocomial infections were significantly more frequent during chemotherapy in RS followed by AC group (p＝0.042). Our data also showed that patients who were administered NC prior to RS significantly have better PFS as well as OS (P=0.002 and 0.018, respectively).
Conclusion: As compared with RS followed by AC, our results indicated that, without increasing surgical complications and chemo-toxicity, the application of NC prior to RS has a significant improvement on the pathologic stage as well as the length of the PFS and OS period of Taiwanese population affected by AUC.

並列關鍵字

neoadjuvant chemotherapy ； advanced urothelial carcinoma ； survival rate

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