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转移性前列腺癌 - 版本历史
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<strong>[[转移性前列腺癌]]</strong>（[[Metastatic Prostate Cancer|mPCa]]）是前列腺癌的晚期形式，表现为肿瘤细胞突破前列腺包膜，远端播散至 <strong>[[骨骼]]</strong>（最常见，约占 90%）、远端 <strong>[[淋巴结]]</strong> 及内脏器官。临床管理的核心已由单纯的 <strong>[[雄激素剥夺治疗]]</strong>（[[ADT]]）演进为“早期强化治疗”模式，即联合 <strong>[[新型内分泌药物]]</strong>（[[NHT]]）或 <strong>[[化疗]]</strong>。随着 <strong>[[PSMA]]</strong> 靶向诊疗及 <strong>[[PARP 抑制剂]]</strong> 的应用，[[转移性前列腺癌]] 已逐渐向“慢性病”管理模式转变。<br />
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<div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1.2px;">转移性前列腺癌</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">[[Metastatic Prostate Cancer]] (点击展开)</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">前列腺癌典型播散路径</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">临床分期</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">IV 期 (M1)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要阶段</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[mHSPC]] / [[mCRPC]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键标志物</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">[[PSA]], [[PSMA]], [[ALP]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">常见转移部位</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[骨转移]] (中轴骨)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">一线治疗</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #166534;">[[双联疗法]] / [[三联疗法]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">ICD-10</th><br />
<td style="padding: 6px 12px; color: #0f172a;">C61</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：定植与微环境转换</h2><br />
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前列腺癌的转移是一个复杂的“种子与土壤”交互过程，涉及多个分子特征：<br />
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<li style="margin-bottom: 12px;"><strong>[[骨向性|成骨性转移]]：</strong> 前列腺癌细胞通过分泌 <strong>[[BMPs|骨形态发生蛋白]]</strong> 和 <strong>[[ET-1|内皮素-1]]</strong>，诱导 <strong>[[成骨细胞]]</strong> 异常激活。这种成骨性改变（Osteoblastic）是其区别于[[肺癌]]（多为溶骨性）的显著特征。</li><br />
<li style="margin-bottom: 12px;"><strong>[[AR 轴|AR 轴持续激活]]：</strong> 即使在 [[转移性]] 阶段，<strong>[[雄激素受体]]</strong>（[[AR]]）信号仍是肿瘤生长的引擎。肿瘤细胞通过 <strong>[[AR 扩增]]</strong> 或 <strong>[[AR 突变]]</strong> 实现对低雄激素环境的适应。</li><br />
<li style="margin-bottom: 12px;"><strong>[[上皮-间质转化]] (EMT)：</strong> 肿瘤细胞通过下调 <strong>[[E-钙粘蛋白]]</strong>（[[E-cadherin]]）并上调 <strong>[[波形蛋白]]</strong>（[[Vimentin]]），获得迁移和抗[[凋亡]]能力。</li><br />
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<h2 style="background: #fff1f2; color: #9f1239; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #9f1239; font-weight: bold;">临床分类：mHSPC 与 mCRPC</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; width: 20%;">特征维度</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; width: 40%;"><strong>[[mHSPC]]</strong> (激素敏感期)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; width: 40%;"><strong>[[mCRPC]]</strong> (去势抵抗期)</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">治疗反应</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">对单纯去势治疗（[[ADT]]）有反应</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #b91c1c;">去势水平下病情仍进展</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[PSA]] 动态</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">通常迅速下降</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">持续上升或影像学进展</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">核心目标</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">延缓向 [[CRPC]] 转化</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">延长生命，缓解[[骨痛]]</td><br />
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<h2 style="background: #f0fdf4; color: #166534; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #166534; font-weight: bold;">治疗策略：从单药到三联强攻</h2><br />
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<h3 style="margin-top: 0; color: #14532d; font-size: 1.1em;">mHSPC 阶段的强化治疗</h3><br />
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<li><strong>[[三联疗法]] (Triplet)：</strong> [[ADT]] + <strong>[[多西他赛]]</strong> + <strong>[[醋酸阿比特龙]]</strong>（或达罗他胺）。针对高负荷、新诊断患者。</li><br />
<li style="margin-top: 10px;"><strong>[[双联疗法]] (Doublet)：</strong> [[ADT]] 联合一种 [[新型内分泌药物]]（如 [[恩扎卢胺]]、阿帕他胺）。</li><br />
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<h3 style="margin-top: 0; color: #b45309; font-size: 1.1em;">mCRPC 阶段的精准打击</h3><br />
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<li><strong>核素疗法：</strong> <strong>[[Lu-177-PSMA]]</strong> 针对 PSMA 阳性患者的靶向放疗。</li><br />
<li style="margin-top: 10px;"><strong>[[合成致死]]：</strong> <strong>[[奥拉帕利]]</strong> 针对携带 [[BRCA1/2]] 突变的患者。</li><br />
<li style="margin-top: 10px;"><strong>骨靶向：</strong> <strong>[[镭-223]]</strong> 专门针对症状性骨转移病灶。</li><br />
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<h2 style="background: #f8fafc; color: #334155; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: #64748b 6px solid; font-weight: bold;">核心相关概念</h2><br />
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<li><strong>[[寡转移]] (Oligometastatic)：</strong> 指远端病灶 ≤ 3-5 个，此类患者可能从原发灶或转移灶的 <strong>[[减瘤手术]]</strong> 或 <strong>[[放疗]]</strong> 中获益。</li><br />
<li><strong>[[骨相关事件]] (SREs)：</strong> 包括病理性骨折、脊髓压迫，常联合使用 <strong>[[地舒单抗]]</strong> 进行干预。</li><br />
<li><strong>[[去势水平]]：</strong> 睾酮浓度低于 50 ng/dL。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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[1] <strong>Sweeney CJ, et al. (2015).</strong> <em>Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer (CHAARTED).</em> <strong>[[NEJM]]</strong>.<br><br />
<span style="color: #475569;">[关键证据]：定义了“高负荷”概念并确立了化疗在 mHSPC 中的地位。</span><br />
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[2] <strong>Fizazi K, et al. (2022).</strong> <em>Abiraterone plus Prednisone Added to ADT and Docetaxel in mHSPC (PEACE-1).</em> <strong>[[The Lancet]]</strong>.<br><br />
<span style="color: #475569;">[临床突破]：证实了三联疗法相较于双联疗法显著延长了影像学无进展生存期。</span><br />
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[3] <strong>James ND, et al. (2017).</strong> <em>Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy (STAMPEDE).</em> <strong>[[NEJM]]</strong>.<br><br />
<span style="color: #475569;">[全球标准]：支持将阿比特龙推广至所有新诊断转移性患者的一线治疗。</span><br />
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[[转移性前列腺癌]] · 知识图谱<br />
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<td style="padding: 10px 15px; color: #334155;">[[局部晚期]] → <strong>[[mHSPC]]</strong> → [[mCRPC]] → [[NEPC]]</td><br />
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<td style="width: 90px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle;">[[强化药物]]</td><br />
<td style="padding: 10px 15px; color: #334155;">[[醋酸阿比特龙]] • [[恩扎卢胺]] • [[多西他赛]] • [[达罗他胺]]</td><br />
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<td style="width: 90px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle;">[[先进影像]]</td><br />
<td style="padding: 10px 15px; color: #334155;">[[PSMA PET-CT]] • [[全身 MRI]] • 骨闪烁显像</td><br />
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