第九章、非尿路上皮膀胱癌

• 組織學特性與診斷建議：膀胱癌中約有 5–10% 屬於非尿路上皮組織型態，此類亞型通常具有較高侵略性，且對標準治療的反應差異較大。NCCN 指引建議，對於疑似非尿路上皮組織型態的病例，應儘可能諮詢專科病理醫師以確認診斷。 ^[4]

• 晚期療法選項：Nivolumab 合併 Ipilimumab（Nivolumab：3 mg/kg；Ipilimumab：1 mg/kg，IV Q3W × 4 療程，之後接續 Nivolumab 維持治療 480 mg IV Q4W）。一項納入 19 位非尿路上皮組織型態之膀胱癌或泌尿道癌患者的研究顯示，其整體反應率（ORR）可達 37%。然而，此類患者族群罕見且高度異質，試驗樣本數有限，現階段仍無法全面確認其療效。 ^[58]

9.1 小細胞/神經內分泌癌 (Small Cell/Neuroendocrine)

• 特性：極具侵略性，常早期轉移，生物學行為類似小細胞肺癌 (SCLC)。

• 治療原則：^[4]

  • 全身性治療：不應使用膀胱癌的標準化療，而應採用類似小細胞肺癌的化療療法，如 Etoposide + Cisplatin (EP)或與Ifosfamide + Doxorubicin交替使用。

  • 局部治療：對於侷限性疾病，術前輔助化療後接續手術或放射治療是標準做法。

  • 腦部預防：由於高腦轉移風險，建議進行腦部 MRI 篩檢。

9.2 純鱗狀細胞癌 (Pure Squamous Cell Carcinoma)

• 特性：與慢性刺激 (如血吸蟲感染、長期導尿管、結石) 有關。對傳統化療及免疫治療反應差。

• 治療原則：^[4]

  • 局部疾病：以根除性膀胱切除術為主。術前/術後化療的角色不明確。

  • 轉移性疾病：目前無標準化療療法，可考慮Paclitaxel, Ifosfamide, Cisplatin等藥物，或鼓勵參加臨床試驗。

9.3 純腺癌 (Pure Adenocarcinoma)

• 包括：臍尿管腺癌 (Urachal carcinoma) 及非臍尿管腺癌。

• 治療原則^[4]

  • 臍尿管腺癌：首選部分或根除性膀胱切除術，並需整塊切除臍尿管韌帶及肚臍 (En-bloc resection) 。

  • 轉移性疾病：化療療法通常參考大腸直腸癌的治療指引 (如 FOLFOX, FOLFIRI) 或使用 5-FU, Gemcitabine, Cisplatin。因為這些腫瘤在基因表現上更接近腸道腫瘤。

總結與展望

• 根據區域效應學說（field cancerization theory），尿路上皮細胞長期暴露並浸泡於含致癌物質的尿液中，因而逐漸產生癌變。臨床上，膀胱癌依腫瘤侵犯深度由內而外分為三大類：非肌肉侵犯性膀胱癌（NMIBC）、肌肉侵犯性膀胱癌（MIBC），以及轉移性膀胱癌（MBC）。

• 診斷流程需整合膀胱鏡檢查、經尿道膀胱腫瘤切除術 (TURBT) 與病理切片，並應特別警覺如微乳頭狀、漿細胞樣或小細胞癌等具備高度侵襲性的特殊組織亞型。

• NMIBC的治療核心在於完整的手術切除腫瘤病灶，並配合卡介苗（BCG）或化學治療藥物（如 Gemcitabine）進行膀胱內灌注治療，以因應其高復發風險，並預防疾病進展至肌肉侵犯階段。

• 針對MIBC，黃金標準治療為根治性膀胱切除術合併淋巴結清除，且強烈建議配合術前輔助化療 (ddMVAC) 或新型的EV + Pembrolizumab 圍手術期療法以降低微觀轉移風險 。

• 轉移性膀胱癌的一線治療已迎來重大變革，EV + Pembrolizumab (EV+P) 組合療法顯著突破了生存屏障，成為不論患者是否適合順鉑 (Cisplatin) 的新一代黃金標準。

• 精準醫療在後線治療中扮演關鍵角色，透過基因檢測篩選FGFR變異或HER2表達的患者，可選用 Erdafitinib 或標靶抗體藥物複合體 (ADC) 提供更有效的個體化選擇。

• 除了對不同分期的患者實施長期的影像與內視鏡監測外，針對罕見的非尿路上皮癌 (如鱗狀細胞癌或腺癌)，則需跳脫傳統尿路上皮癌的治療框架，採取更具針對性的個別化處置策略。

作者：癌症資訊雜貨店 傅彥崴 藥師

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