由婦科腫瘤醫師、放射腫瘤醫師、病理部醫師、放射診斷部醫師、核子醫學部醫師參與而形成共識 高雄榮總 子宮頸癌診療指引 由婦科腫瘤醫師、放射腫瘤醫師、病理部醫師、放射診斷部醫師、核子醫學部醫師參與而形成共識
修訂指引 本共識依下列參考資料修改版本 NCCN Clinical Practical Guidelines in Oncology TM Cervical Cancer (Version1,2009) 婦癌研究委員會(2007),子宮頸癌篩檢臨床指引與子宮頸癌臨床指引:國家衛生研究院
會議討論日期 上次會議:9801?? , 980910 本共識與上一版的差異 討論後由劉正彬醫師完成文字紀錄,再交給各位核心成員審視
高雄榮總婦癌團隊 子宮頸原位癌臨床治療指引 3-6個月再行一次抹片檢查或/及陰道鏡檢或 6-12個月行人類乳突病毒檢查 標本邊緣無病變 無生育考量 全子宮切除 3-6個月再行一次抹片檢查或/及陰道鏡檢或 6-12個月行人類乳突病毒檢查, 或加上子宮內刮搔術後至少6個月抹片檢查(AIS) 子宮頸原位癌 (CIS, AIS)行子宮頸錐形切片後 欲保留子宮 無生育考量 全子宮切除 標本邊緣有病變 3-6個月再行一次抹片檢查或/及陰道鏡檢或 6-12個月行人類乳突病毒檢查 欲保留子宮
高雄榮總婦癌團隊 子宮頸癌臨床治療指引 子宮頸癌治療流程 高雄榮總婦癌團隊 子宮頸癌臨床治療指引 子宮頸癌治療流程 治療前檢查:1.病史及理學檢查;2.全血球計數;3.子宮頸切片之組織病理檢查;4.子宮頸錐狀手術+子宮頸管搔刮術(當子宮 頸切片之組織病理檢查結果為微侵襲癌者);5.胸部X光;6.分期高於IA者,安排腹部及骨盆電腦斷層;7.常規生 化檢驗; 8. 血清腫瘤標記檢驗(鱗狀細胞癌者:SCC、CEA;腺癌者:CEA、CA─125) 選擇性檢查:#分期為IB2或以上者,膀胱或直腸鏡檢;#葡萄糖正子攝影 無淋巴結轉移,無陰道切除邊緣侵襲且子宮旁組織侵襲 輔助治療 1.筋膜外子宮切除 2.欲保留生育能力者或不適合手術者,於子宮頸錐狀手術後 密集追蹤觀察 FIGO分期IA1 觀察 化學治療四次(血管淋巴侵犯)或六次(淋巴侵犯) 1.較小範圍根治性子宮切除術及骨盆淋巴結摘除術,或併主動脈旁淋巴結取樣(選擇性 , 尚無定論) 2.近接治療(Brachytherapy)或併骨盆放射線治療@ FIGO分期IA2 淋巴結轉移或血管淋巴侵犯者 手術標本組織病理檢查 同步化放療@ FIGO分期IB1或IIA1 1.根治性子宮切除術*及骨盆淋巴結摘除術,或合併主動脈旁淋巴結取樣 2.骨盆放射線治療及近接治療(Brachytherapy)@ 陰道切除邊緣侵襲或子宮旁組織侵襲或手術中腫瘤破裂 放射線治療@ 1.根治性子宮切除術*及骨盆淋巴結摘除術,合併主動脈旁淋巴結取樣 2.骨盆放射線治療@及近接治療@同時合併含cisplatin之治療+/-子宮切除(ATH or RH) 3.術前輔助性化學治療及根治性子宮切除術及骨盆淋巴結摘除術,合併主動脈旁淋巴結取樣 FIGO分期IB2或IIA2 淋巴結轉移或血管淋巴侵犯者及陰道切除邊緣侵襲或子宮旁組織侵襲或手術中腫瘤破裂 化學治療三次放射線治療@ 化學治療三次 同步化放療@ 手術治療:*含神經保留式根治性子宮切除術(nerve sparing radical hysterectomy) @: 放射治療或同步化放療請見放射腫瘤部治療指引 圖一
高雄榮總婦癌團隊 子宮頸癌臨床治療指引 FIGO分期IIB-IVA(局部晚期)子宮頸癌,或不適合施行根治性子宮切除手術之IB 、IIA治療流程 1.放射治療包括體外放射治療及近接治療@ 2.同步化放療時使用含cisplatin 40 mg/m2 weekly x 6 courses 之化療或臨床試驗 影像檢查無淋巴結病變 同時合併化療及骨盆或併主動脈旁淋巴結放射治療@ 1.FIGO分期IB2,IIA2(腫瘤> 4cm或高度懷疑子宮頸基質深度侵襲,或身體狀況不適合接受根治性子宮切除手術者) 2.FIGO分期IIB-IVA 選擇個案 骨盆淋巴結轉移/無主動脈旁淋巴結轉移 全身性化學治療 影像檢查呈淋巴結病變 影像檢查:骨盆及腹部電腦斷層或核磁共振檢查 選擇個案 同時合併化療及骨盆併主動脈旁淋巴結放射治療@ 主動脈旁淋巴結轉移 胸部電腦斷層無轉移病灶 胸部電腦斷層 骨盆外疾病 切片呈陰性 胸部電腦斷層呈轉移病灶 全身性化學治療或併選擇性放射治療@ 切片呈陽性 圖二 @: 放射治療或同步化放療及併主動脈旁淋巴結放射治療請見放射腫瘤部治療指引
高雄榮總婦癌團隊 子宮頸癌臨床治療指引 子宮頸癌治療後追蹤及復發的處置 定期追蹤方法 進一步檢查 救援性(Salvage)治療 高雄榮總婦癌團隊 子宮頸癌臨床治療指引 子宮頸癌治療後追蹤及復發的處置 定期追蹤方法 進一步檢查 救援性(Salvage)治療 骨盆放射線治療或併化學治療 侷限於小範圍的復發性病灶,可考慮手術治療 未接受過放射治療者 1.理學檢查 2.抹片檢查:治療後兩年內每三個月一次,第三年每四個月一次,第四至五年每六個月一次,以後每年一次 3.腫瘤標記(鱗狀細胞癌者:SCC、CEA;腺癌者:CEA、CA─125) 4.全血(CBC)及腎功能(BUN、Cr)檢驗,有必要時可每六個月檢驗一次 5.胸部X光檢查及電腦斷層檢查,有必要時可每年安排檢查一次 1.骨盆及腹部電腦 斷層檢查 2.胸部X光檢查(若為陰性,則考慮胸部電腦斷層檢查) 3.技術可行下,考慮直接切片或超音波或電腦斷層指引下切片 4.有必要時可以施行手術探查 僅骨盆腔內復發 復發病灶未達骨盆壁者: 1.骨盆腔臟器宛除術 2.如病灶僅侷限於子宮頸,可施行根治性子宮切除術或間質放射線治療 已接受過放射治療者 復 發 懷疑持續性或復發性疾病 復發病灶已達骨盆壁者: 以鉑(Platinum)為主之化療或緩解/支持性治療或臨床試驗 多處復發或無法切除者 以鉑(Platinum)為主之化療或緩解/支持性治療或臨床試驗 骨盆腔外復發 1.局部病灶切除(肺臟或肝臟或腸道或淋巴等) 2.放射線治療或 3.化學治療 4.同步化放療 單處復發者 圖三
高雄榮總婦癌團隊 子宮頸癌臨床治療指引 單純子宮全切除後意外發現侵襲性癌症 輔助治療 追加治療 高雄榮總婦癌團隊 子宮頸癌臨床治療指引 單純子宮全切除後意外發現侵襲性癌症 輔助治療 追加治療 無淋巴結轉移,無陰道切除邊緣侵襲且無子宮旁組織侵襲 觀察 子宮頸旁組織全切除及部分陰道切除(complete parametrectomy)及骨盆淋巴結摘除或併主動脈旁淋巴結摘除 化學治療四次(血管淋巴侵犯)或六次(淋巴侵犯) 手術標本組織病理檢查 淋巴結轉移或血管淋巴侵犯者 組織病理分期≧ IA2 同步化放療 陰道切除邊緣侵襲或子宮旁組織侵襲或手術中腫瘤破裂 @放射線治療 (組織邊緣無侵犯且影像檢查陰性 )或同步化放療(組織邊緣侵犯陰道端明顯殘留腫瘤或影像檢查陽性) 放射線治療 化學治療三次放射線治療 化學治療三次 陰道切除邊緣侵襲或子宮旁組織侵襲或手術中腫瘤破裂合併淋巴結轉移或血管淋巴侵犯者 組織病理分期IA1 病理審閱後,如無淋巴血管間隙侵犯可觀察 病理審閱後,如有淋巴血管間隙侵犯, 要安排影像學檢查, 診療方式與組織病理分期≧ IA2者相同 同步化放療 @: 放射治療或同步化放療及併主動脈旁淋巴結放射治療請見放射腫瘤部治療指引 圖四
高雄榮總婦癌團隊 子宮頸癌臨床治療指引-化學治療 高雄榮總婦癌團隊 子宮頸癌臨床治療指引-化學治療 術前輔助性化學治療或手術後輔助治療以platinum-based 為主的治療為原則可使用以下的選擇 IP (ifofamide/platinum) - 第一線 Topotecan/platinum -第二線 Paclitaxel/platinum -第三線 Irrinotecan/platinum -第四線 Clinical trials 小細胞或神經內分泌癌術前輔助性化學治療或手術後輔助治療以platinum-based 為主的治療為原則可使用以下的選擇 1. VP-16/cyclophosphamide/platinum 第IV期B,持續性疾病 (persistent disease)復發或轉移性疾病 (recurrent or metastatic disease)之全身性化學治療以platinum-based 為主的治療為原則可使用以下的選擇 Topotecan/platinum -第一線 IP (ifofamide/platinum) - 第二線 Paclitaxel/platinum -第三線 Irrinotecan/platinum -第四線 Clinical trials
References 1. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2006. CA Cancer J Clin 2006;56:106-130. 2. Edwards BK, Brown ML, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975-2002, featuring populationbased trends in cancer treatment. J Natl Cancer Inst 2005;97:1407-1427. 3. Parkin DM, Bray F, Ferlay J. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. 4. American College of Obstetricians and Gynecologists. ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas. Number 35, May 2002. Int J Gynaecol Obstet 2002;78:79-91. 5. Chi DS. Laparoscopy in gynecologic malignancies. Oncology 1999;13:773-782. 6. Benedet JL, Bender H, Jones H 3rd, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000;70:209-262. 7. Landoni F, Maneo A, Colombo A, et al. Randomized study of radical surgery vs. radiotherapy for stage Ib-IIa cervical cancer. Lancet 1997;350:535-540. 8. Haie-Meder C, Fervers B, Fondrinier E, et al. SOR guidelines for concomitant chemoradiotherapy for patients with uterine cervical cancers: evidence update bulletin 2004. Ann Oncol 2005;16:1100-1108. 9. Koliopoulos G, Sotiriadis A, Kyrgiou M, et al. Conservative surgical methods for FIGO stage IA2 squamous cervical carcinomaand their role in preserving women's fertility. Gynecol Oncol2004;93:469-473. 10. Bernardini M, Barrett J, Seaward G, et al. Pregnancy outcomes in patients after radical trachelectomy. Am J Obstet Gynecol 2003;189:1378-1382. 11. Boss EA, van Golde RJ, Beerendonk CC, et al. Pregnancy after radical trachelectomy: A real option? Gynecol Oncol 2005;99:S152- 6. Epub 2005 Sep 2. 12. Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154-1161. 13. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999;340:1137-1143. 14. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606-1613.
References 15. Pierluigi Benedetti-Panici, Stefano Greggi, Alessandro Colombo et al. Neoadjuvant Chemotherapy and Radical Surgery Versus Exclusive Radiotherapy in Locally Advanced Squamous Cell Cervical Cancer: Results From the Italian Multicenter Randomized Study. JCO Jan 1 2002: 179-188. 16. By Ting-Chang Chang, Chyong-Huey Lai, Ji-Hong Hong et al. Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. Journal of Clinical Oncology, Vol 18, Issue 8 (April), 2000: 1740-1747 17. Sardi J, Sananes C, Giaroli A et al. Results of a prospective randomized trial with neoadjuvant chemotherapy in stage IB, bulky, squamous carcinoma of the cervix. Gynecol Oncol. 1993 May;49(2):156-65 18. Juan E. Sardi, Adolfo Giaroli, Carlos Sananes et al. Long-Term Follow-up of the First Randomized Trial Using Neoadjuvant Chemotherapy in Stage Ib Squamous Carcinoma of the Cervix: The Final Results. Gynecologic Oncology, Volume 67, Issue 1, October 1997, Pages 61-69. 19. Gary L. Eddy, Brian N. Bundy, William T. Creasman et al. Treatment of (“bulky”) stage IB cervical cancer with or without neoadjuvant vincristine and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: A phase III trial of the gynecologic oncology group. Gynecologic Oncology, Volume 106, Issue 2, August 2007, Pages 362-369 20. Frederick B. Stehman, Shamshad Ali, Henry M. Keys et al, Radiation therapy with or without weekly cisplatin for bulky stage 1B cervical carcinoma: follow-up of a Gynecologic Oncology Group trial. American Journal of Obstetrics and Gynecology, Volume 197, Issue 5, November 2007, Pages 503.e1-503.e6 21. Henry M. Keys, Brian N. Bundy, Frederick B. Stehman et al, Radiation therapy with and without extrafascial hysterectomy for bulky stage IB cervical carcinoma: a randomized trial of the Gynecologic Oncology Group. Gynecologic Oncology, Volume 89, Issue 3, June 2003, Pages 343-353 22. Landoni F, Maneo A, Colombo A et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 1997 Aug 23;350(9077):535-40 23. Sedlis A, Bundy BN, Rotman MZ et al. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol. 1999 May;73(2):177-83 24. Peters WA 3rd, Liu PY, Barrett RJ 2nd et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13
References 25. Cosin JA, Fowler JM, Chen MD et al. Pretreatment surgical staging of patients with cervical carcinoma: the case for lymph node debulking. Cancer. 1998 Jun 1;82(11):2241-8 26. Lai CH, Huang KG, Hong JH, et al. Randomized trial of surgical staging (extraperitoneal or laparoscopic) versus clinical staging in locally advanced cervical cancer. Gynecol Oncol. 2003 Apr;89(1):160-7. 27. Perry W. Grigsby. 4th International Cervical Cancer Conference: update on PET and cervical cancer. Gynecologic Oncology, Volume 99, Issue 3, Supplement 1, December 2005, Pages S173-S175 28. Mayr NA, Taoka T, Yuh WT et al. Method and timing of tumor volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2002 Jan 1;52(1):14-22. 29. Rose PG, Adler LP, Rodriguez M et al. Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study. J Clin Oncol. 1999 Jan;17(1):41-5 30. Chou HH, Chang TC, Yen TC et al. Low value of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in primary staging of early-stage cervical cancer before radical hysterectomy. J Clin Oncol. 2006 Jan 1;24(1):123-8 31. Boughanim M, Leboulleux S, Rey A et al. Histologic results of para-aortic lymphadenectomy in patients treated for stage IB2/II cervical cancer with negative [18F]fluorodeoxyglucose positron emission tomography scans in the para-aortic area. J Clin Oncol. 2008 May 20;26(15):2558-61 32. Chao A, Ho KC, Wang CC et al. Positron emission tomography in evaluating the feasibility of curative intent in cervical cancer patients with limited distant lymph node metastases. Gynecol Oncol. 2008 May 20. [Epub ahead of print] 33. Ohara K, Tsunoda H, Satoh T et al. Use of the small pelvic field instead of the classic whole pelvic field in postoperative radiotherapy for cervical cancer: reduction of adverse events. Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):258-64 34. Nobuhiro Takeshima, Kenji Umayahara, Kiyoshi Fujiwara et al. Treatment results of adjuvant chemotherapy after radical hysterectomy for intermediate- and high-risk stage IB–IIA cervical cancer. Gynecologic Oncology, Volume 103, Issue 2, November 2006, Pages 618-622