T3期前列腺癌不适合根治术

T3期前列腺癌适合前列腺癌根治术吗期前列腺癌适合前列腺癌根治术吗?NO中国医科大学附属第一医院 宫大鑫n nRadical prostatectomy was described by Young in 1905 for the treatment of localized prostate cancer.n nDr Patrick WalshDr Patrick Walshn nreviewing the role of radical prostatectomy in the reviewing the role of radical prostatectomy in the cure of prostate cancercure of prostate cancer。n n if the if the tumourtumour is of a high grade,it is unlikely that is of a high grade,it is unlikely that cure can be achieved with any form of treatment.cure can be achieved with any form of treatment.Walsh PC.Radical prostatectomy for the treatment Walsh PC.Radical prostatectomy for the treatment localisedlocalised prostate prostate cancer.cancer.UrolUrol ClinClin North Am North Am 1980;1980;7 7:583:583.cT3前列腺癌现状前列腺癌现状n ncT3前列腺癌约占15%。n ncT3手术切缘阳性率达56%。n ncT3淋巴结转移率达27-50%。n nEven in Even in carefully selected patients with small T3 cancers,seminal vesicle invasion is present in 67%seminal vesicle invasion is present in 67%and lymph node metastases in 20%.and lymph node metastases in 20%.n nOhoriOhori M et al Cancer 1994c;73:104114.M et al Cancer 1994c;73:104114.cT3肿瘤采用根治性前列腺切除术状况肿瘤采用根治性前列腺切除术状况 n n美国Chicagon n新诊断的新诊断的cT12 cT12 期前列腺癌期前列腺癌30%30%采用采用RP.RP.n n有较长预期寿命年轻病人也只有约有较长预期寿命年轻病人也只有约67%67%采用采用RP.RP.n n只用只用6%cT36%cT3前列腺癌前列腺癌采用采用RPRP。n n美国 Mayo clinicn n19831983年采用年采用RPRP比例为比例为25.3%25.3%n n20012001年降为年降为2.8%2.8%。Meltzer Meltzer D,PatternsD,Patterns of of prostate prostate cancer cancer treatment treatment by by clinical clinical stage stage and and age.age.Am Am J J Public Public HealthHealth，2001;91:2001;91:12681268Ward Ward JF.RadicalJF.Radical prostatectomy prostatectomy for for clinically clinically advanced advanced(cT3)(cT3)prostate prostate cancer cancer since since the the advent advent of of prostate-prostate-specific antigen testing:15-year outcome.BJU Int.2005 Apr;95(6):751-6.specific antigen testing:15-year outcome.BJU Int.2005 Apr;95(6):751-6.cT3实际情况实际情况pT215%pT3pT48%术前能准确分期吗？术前能准确分期吗？n nDRE常常低估肿瘤的进展情况。n n一项研究表明一项研究表明DREDRE阳性情况和肿瘤分期符合度阳性情况和肿瘤分期符合度小于小于 50%50%。n n约 60%的pT3在术前不能被TRUS 检测到。n n区分区分 T2T2和和 T3T3不能单纯依靠不能单纯依靠TRUSTRUS。n nPSA和临床分期也没有直接联系。EAU guideline of prostate cancer.2007 RP的目的的目的n nIn men with localized CaP and a life expectancy of 10 years or more,the goal of a radical prostatectomy by any approach must be eradication of the disease.n nThe success of radical prostatectomy for clinical stage T3 prostate cancer relies on the removal of all local tumor-bearing tissue.nHuland H.Scientific Communication International,Jersey,Channel Islands,1997,pp.227-257.nGuidelines on Prostate Cancer(EAU,2007）nCampbells Urology,8th ed反对对反对对T3行行RP的主要原因的主要原因n n生存率n n淋巴结转移n n切缘阳性率 n n 生活质量生存率生存率-T3N0T3N0前列腺癌自然病史前列腺癌自然病史前列腺癌自然病史前列腺癌自然病史n n美国退伍军人管理协会泌尿外科协作研究组数据：美国退伍军人管理协会泌尿外科协作研究组数据：n n5 5年生存率年生存率50%,1050%,10年生存率年生存率20%20%。（接受了一定程度的。（接受了一定程度的内分泌治疗）内分泌治疗）n nAdolfssonAdolfsson报道：报道：n n共共5555例，分化良好前列腺癌。例，分化良好前列腺癌。5 5年生存率年生存率88%88%，9 9年生存年生存率率70%70%。AdolfssonAdolfsson J.Deferred treatment of low grade stage T3 prostate cancer without J.Deferred treatment of low grade stage T3 prostate cancer without distant distant metastases.Jmetastases.J UrolUrol.1993 Feb;149(2):326-8.1993 Feb;149(2):326-8 生存率生存率-T3N0T3N0前列腺癌自然病史前列腺癌自然病史前列腺癌自然病史前列腺癌自然病史n n有些系列报道T3期肿瘤,未用附加治疗5年及10年生存率为68%-92%及55%-88%。n n一组接受附加治疗661例无肿瘤进展病人的5年、10年及15年生存率为74%，50%及42%。n n相当一部分T3肿瘤可以有较长时期生存。n n如果采取了放疗，内分泌治疗，可能会有更好的效果。生存率生存率-根治性前列腺切除术后效果根治性前列腺切除术后效果根治性前列腺切除术后效果根治性前列腺切除术后效果 n n局限于前列腺内肿瘤，根治术后：n n5 5年无肿瘤复发生存率为年无肿瘤复发生存率为90%90%以上。以上。n n有精囊累及或者淋巴转移的前列腺癌：n n5 5年和年和1010年无瘤生存率分别为年无瘤生存率分别为76%76%和和71%71%。Hull G,Hull G,RabbaniRabbani F,F,AbbasAbbas F,et al:Cancer control with radical prostatectomy alone in 1000 F,et al:Cancer control with radical prostatectomy alone in 1000 consecutive patients.J consecutive patients.J UrolUrol,in press,2001,in press,2001T3期PCa单独接受RP 美国多中心美国多中心美国多中心美国多中心cT3cT3期回顾性总结期回顾性总结期回顾性总结期回顾性总结298298例患者。例患者。例患者。例患者。1010年癌特异性和无转移生存率分别为年癌特异性和无转移生存率分别为年癌特异性和无转移生存率分别为年癌特异性和无转移生存率分别为5757和和和和3232。高高高高、中中中中、低低低低分分分分化化化化患患患患者者者者的的的的1010年年年年癌癌癌癌特特特特异异异异性性性性生生生生存存存存率率率率分分分分别别别别 为为为为7373、6767、2929。对对对对pT3pT3期患者单用手术治疗难以获得长期生存期患者单用手术治疗难以获得长期生存期患者单用手术治疗难以获得长期生存期患者单用手术治疗难以获得长期生存,对对对对于于于于cT3cT3期期期期患患患患者者者者，只只只只有有有有中中中中高高高高分分分分化化化化的的的的部部部部分分分分病病病病例例例例可可可可从从从从 根治手术中获益。根治手术中获益。根治手术中获益。根治手术中获益。Gerber GS,et al.Gerber GS,et al.EurEur UrolUrol.1997;32(4):385.1997;32(4):385.T3期PCa单独接受RP 8383例例例例cT3cT3期期期期PCaPCa,RP,RP为单一治疗为单一治疗为单一治疗为单一治疗:5 5年年年年 1010年年年年 术后总生存率术后总生存率术后总生存率术后总生存率 7575 6060 肿瘤特异性生存率肿瘤特异性生存率肿瘤特异性生存率肿瘤特异性生存率 8585 7272 临床进展率临床进展率临床进展率临床进展率 4141 6969 局部复发率局部复发率局部复发率局部复发率 1818 4444 远处转移率远处转移率远处转移率远处转移率 3131 5050 生化进展率生化进展率生化进展率生化进展率 7171OudenOuden D VD,et al.J D VD,et al.J UrolUrol 1998;160(4):1392.1998;160(4):1392.Catalona WJ,Smith DS:Cancer recurrence and survival rates after anatomic radical retropubic prostatectomy for prostate cancer:Intermediateterm results.J Urol 1998;160:2428-2434.796644临床分期临床分期J Urol.2002 Feb;167(2 Pt 1):528-34.Cancer control with radical prostatectomy alone in 1,000 consecutive patients.Hull GW,Rabbani F,Abbas F,Wheeler TM,Kattan MW,Scardino PT.T3期PCa RP 优于EBRT？T3期PCa：RP vs EBRT 1.1.US,US,多中心多中心多中心多中心回顾性分析回顾性分析回顾性分析回顾性分析298298例例例例cT3 cT3 PCaPCa单独单独单独单独RPRP 2.2.US,US,1975197519921992年年年年PCaPCa单单单单用用用用EBRTEBRT,15571557例例例例(59(59)cT3)cT3.10年年CSS GS 2-5 GS 5-7 GS 8-10 RP 1 73 67 29 EBRT2 87 75 44 1.1.Gerber GS,et al.Gerber GS,et al.EurEur UrolUrol.1997;32(4):385.1997;32(4):385.2.2.Roach M 3rd,et al.J Roach M 3rd,et al.J UrolUrol.1999;161(3):864.1999;161(3):864.RP VS EBRT+HTn n5年生存率没有差别。n nRP远期致残率较高，生活质量较低。n nAkakura K。Urology.1999 Aug;54(2):313-8.淋巴结转移淋巴结转移n nZinckeZincke等认为：等认为：n n不能完全切除肿瘤；不能完全切除肿瘤；n n较高的淋巴结转移率。较高的淋巴结转移率。n nGervasGervas等认为：等认为：n n可触及肿瘤累及精囊的前列腺癌淋巴结转移可达可触及肿瘤累及精囊的前列腺癌淋巴结转移可达30%30%-50%-50%。n nOhoriOhori M M等认为：等认为：n n在某些严格选择的在某些严格选择的T3T3病人病人,精囊受累可达精囊受累可达67%67%，淋巴，淋巴结转移可达结转移可达20%20%。ZinckeZincke H,H,UtzUtz DC,Taylor WF:Bilateral pelvic DC,Taylor WF:Bilateral pelvic lymphadenectomylymphadenectomy and radical prostatectomy for clinical stage C and radical prostatectomy for clinical stage C prostaticprostatic cancer:role of adjuvant treatment for residual cancer and in disease progression.J cancer:role of adjuvant treatment for residual cancer and in disease progression.J UrolUrol 1986;135:1199 1986;135:11991205.1205.GervasiGervasi LA,Mata J,Easley JD,et al:Prognostic significance of lymph nodal metastases in prostate cancer.J LA,Mata J,Easley JD,et al:Prognostic significance of lymph nodal metastases in prostate cancer.J UrolUrol 1989;142:332336.1989;142:332336.OhoriOhori M,Wheeler TM,M,Wheeler TM,ScardinoScardino PT:The new American Joint Committee on Cancer and International Union Against PT:The new American Joint Committee on Cancer and International Union Against Cancer TNM classification of prostate cancer.Cancer 1994c;73:104114.Cancer TNM classification of prostate cancer.Cancer 1994c;73:104114.淋巴结转移淋巴结转移-生存率生存率 5年 10年n n pT3a,b N0 76.2 71.4n n pT3c N0 37.4 37.4n n pT1-3 N+18.6 7.4Catalona WJ,Smith DS:Cancer recurrence and survival rates after anatomic radical retropubic prostatectomy for prostate cancer:Intermediateterm results.J Urol 1998;160:2428-2434.81762619切缘阳性切缘阳性n n切缘阳性是影响前列腺癌根治术患者长期存活的重要因素n ncT3a Pca RP：切缘阳性33.5-66%。n n切缘阴性，5年无疾病进展生存率81-83%。n n切缘阳性，5年无疾病进展生存率58-64%n nJoniauJoniau S.S.EurEur UrolUrol.2007;51(2):388-94;.2007;51(2):388-94;n nGerber GS,et al.Gerber GS,et al.EurEur UrolUrol.1997;32(4):385.1997;32(4):385.n nPilepichPilepich MV.IntMV.Int J Radiation J Radiation OncolOncol BiolBiol Phys,2001;50:1243 Phys,2001;50:12435252nGleave ME。Urology 2000;56:28994切缘阳性切缘阳性J Urol.2002 Feb;167(2 Pt 1):528-34.Cancer control with radical prostatectomy alone in 1,000 consecutive patients.Hull GW,Rabbani F,Abbas F,Wheeler TM,Kattan MW,Scardino PT.NHT+RP能降低cT3术后切缘阳性率？NHT+RP与单独RP比较NHTNHT对对T2T2期期术后切缘阳性率的影响术后切缘阳性率的影响 有明显降期作用有明显降期作用有明显降期作用有明显降期作用 n NHTn NHT组组组组(月月月月)单纯手术组单纯手术组单纯手术组单纯手术组Fair 8%(3)34%Fair 8%(3)34%LabrieLabrie 13%(3)38%13%(3)38%SolowaySoloway 138 18%(3)48%138 18%(3)48%MontironiMontironi 259 31%(3)58%259 31%(3)58%8%(6)8%(6)Meyer 680 25%(3)47%Meyer 680 25%(3)47%Van Van PH PH 19.4%45.9%(19.4%45.9%(后外侧后外侧后外侧后外侧)27%13.9%(27%13.9%(尖部尖部尖部尖部)NHT对T3期术后切缘阳性率的影响 没有明显降期作用，有的反而增高。没有明显降期作用，有的反而增高。没有明显降期作用，有的反而增高。没有明显降期作用，有的反而增高。n NHTn NHT组组组组(月月月月)单纯手术组单纯手术组单纯手术组单纯手术组WitjesWitjes 155 43%(3)59%(P0.05)155 43%(3)59%(P0.05)Van Van PH PH 48.3%(3)40.0%(48.3%(3)40.0%(后外侧后外侧后外侧后外侧)51.7%(3)28.0%(51.7%(3)28.0%(尖部尖部尖部尖部)31.0%(3)8.0%(31.0%(3)8.0%(基底部基底部基底部基底部)1.1.WitjesWitjes WP,Urology,1997,49(3A WP,Urology,1997,49(3A SupplSuppl):65-69.):65-69.2.Van PH,et al.J Urol,1995,154:429-434.2.Van PH,et al.J Urol,1995,154:429-434.NHT治疗使T3期术后切缘阳性率增高的原因 NHT治治疗疗后后淋淋巴巴细细胞胞明明显显浸浸润润，使使间间质质成成分分增增加加，引引起起前前列列腺腺与与周周围围组组织织粘粘连连和和纤纤维维化化，从从而而使使前前列列腺腺尖尖部部和和基基底底部部切切除除不不彻彻底底，使使切切缘缘阳阳性性率率增高。增高。Van PH,et al.J Urol,1995,154:429-434.Van PH,et al.J Urol,1995,154:429-434.NHT治疗对T2及T3期PCa的效果 使使T2期降期，期降期，T3期不肯定。期不肯定。使使T2期期根根治治术术后后标标本本切切缘缘阳阳性性率率降降低低，但对但对T3期不肯定期不肯定 n nJohn F.Ward 认为NHT：n n对对cT3cT3分级，分期和切缘阳性率无明显改善。分级，分期和切缘阳性率无明显改善。n n对无疾病进展生存率和肿瘤特异生存率无影响。对无疾病进展生存率和肿瘤特异生存率无影响。Ward JF.BJU Int.2005;95(6):751-6.Ward JF.BJU Int.2005;95(6):751-6.RP+EBRT?n nRP术后切缘阳性的处理，什么是最好的方法目前还没有达成共识。n n切缘阳性，表明肿瘤已经进展，可以采用EBRT。n n研究表明RP+EBRT在疾病无进展生存率方面有所改善，但是在总体生存率没有优势。n nMasood A.Khan.Int bju 2005,95:281-284RP+AHT可以改善生存率？T3期PCa：RP+AHT vs RT+AHT 回顾分析回顾分析回顾分析回顾分析1992199220032003年年年年209209例例例例cT3 cT3 PCaPCa患者患者患者患者:5 5年年年年OSOS 1010年年年年OS 5OS 5年年年年CSS 10CSS 10年年年年CSSCSSRPRPHTHT 87.3%66.587.3%66.5 93.8%93.8%71.4%71.4%EBRTEBRTHTHT 94.9%70.094.9%70.0 96.6%96.6%9393.6 6 Saito T,et al.Asian J Saito T,et al.Asian J AndrolAndrol.2006;8(5):555.2006;8(5):555.n nLaverdiere 对cT3-4 Pca 进行前瞻性研究n nNHT+EBRT,NHT+EBRT,两年后穿刺活检，两年后穿刺活检，66%(-)66%(-)。n nNHT+EBRT+AHT,NHT+EBRT+AHT,两年后穿刺活检两年后穿刺活检,95%(-),95%(-)。n nLaverdiere J.Int J Radiation Oncol Biol Phys 1997;37:24752RP手术并发症手术并发症Guidelines on Prostate Cancer（EAU,2007）死亡率死亡率死亡率死亡率2.1%2.1%n nDP,DP,KhooKhoo VS,Norman AR,Meyer L,Nahum A,VS,Norman AR,Meyer L,Nahum A,TaitTait D,et al.Comparison of radiation side-effects of D,et al.Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer:a conformal and conventional radiotherapy in prostate cancer:a randomisedrandomised trial.Lancet trial.Lancet 1999;353:267-72.1999;353:267-72.n nPotoskyPotosky AL,AL,LeglerLegler J,J,AlbertsenAlbertsen PC,Stanford JL,Gilliland FD,Hamilton AS,et al.Health outcomes PC,Stanford JL,Gilliland FD,Hamilton AS,et al.Health outcomes after prostatectomy or radiotherapy for prostate cancer:results from the Prostate Cancer Outcomes after prostatectomy or radiotherapy for prostate cancer:results from the Prostate Cancer Outcomes Study.J Study.J NatlNatl Cancer Inst 2000;92:1582-92.Cancer Inst 2000;92:1582-92.n nT2保留神经的RP有较高的局部复发率。n nT3风险更大。Guidelines on Prostate Cancer（EAU,2007）T3期PCa采取何种治疗手段？从循证医学角度看问题从循证医学角度看问题n nIn the absence of data from randomized clinical trials comparing possible options for definitive therapy in these patients,only single or multicentre reports can be used to define the role of radical prostatectomy in this stage.一项比较性研究一项比较性研究n n14年(1983-1997)，medline收录148篇治疗T3期肿瘤文献。n n单一治疗方式：n n放疗和根治性前列腺切除术：任何一种治疗放疗和根治性前列腺切除术：任何一种治疗方式都不可能治愈方式都不可能治愈cT3cT3前列腺癌。前列腺癌。n n任何一种治疗方式都没有表现出优越内分泌任何一种治疗方式都没有表现出优越内分泌治疗的优势。治疗的优势。Peneau M,Pichaud T,Cariou G,et al.Clinical stage T3 prostate cancer:natural history,therapeutic choices and their resultsProg Urol.1998 Dec;8(6):977-93.一项比较性研究一项比较性研究n n联合治疗：n n放疗联合内分泌治疗：研究表明二者联合有较放疗联合内分泌治疗：研究表明二者联合有较好的治疗效果。好的治疗效果。n n根治性前列腺切除术联合内分泌治疗：新辅助根治性前列腺切除术联合内分泌治疗：新辅助内分泌治疗没有表现出明显的优势。内分泌治疗没有表现出明显的优势。n n根治性前列腺切除术联合辅助放疗没有明显优根治性前列腺切除术联合辅助放疗没有明显优势。势。T3,N0,M0T3,N0,M0肿瘤治疗方式的选择决定于病人的状肿瘤治疗方式的选择决定于病人的状态和预期寿命。态和预期寿命。Peneau M,Pichaud T,Cariou G,et al.Clinical stage T3 prostate cancer:natural history,therapeutic choices and their resultsProg Urol.1998 Dec;8(6):977-93.n nEBRT+AHT可以提高cT3 Pca局部进展和远处转移的控制，显著改善生存率。n n美国国家癌症研究所推荐对cT3 Pca采用EBRT+AHT作为首选治疗手段。1.Pilepich MV.Urology 1995;45:616232.Syed S.Urol Oncol 2003;21:235433.Seidenfeld J.Evid Rep Technol Assess(Summ)1999;4:12464.National Cancer Institute.Stage III Prostate Cancer.Available at:http:/www.nci.nih.gov/cancertopics/pdq/treatment/prostate/HealthProfessional/page7Guidelines on Prostate Cancer（EAU,2007）n nSurgical treatment of clinical stage T3 CaP is traditionally discouraged,mainly because patientshave an increased risk of positive surgical margins and lymph node metastases and/or distant relapse.nCombination treatment with hormonal and radiation therapy is gaining popularitycT3 PCa治疗趋势DenburgDenburg TD,et al.BJU TD,et al.BJU IntInt 2006,98:35.2006,98:35.40.340.3%60.2%60.2%18.118.1%9.3%9.3%50%5Xn n近6年cT3 Pca 局部进展控制得到了明显的改善。n n原因是RP的减少，EBRT的增加。Denburg TD,et al.BJU Int 2006,98:35.结论结论n nT3前列腺癌淋巴结转移，手术切缘阳性率较高，生存率相对较差。n nRP不可能完全根治该期肿瘤，没有循证医学有效证据表明：其他附加治疗手段可以显著提高生存率。n n有限的证据表明RP对某些特定T3有略好的治疗效果，但考虑到相对较高的致死率和致残率，也不主张采用RP。conclusionn nRadical prostatectomy is the best treatment for prostate cancer in the right patient.nRadical prostatectomy should be reserved for men who are likely to be cured and will live long enough to benefit from the cure.nit is the doctor who makes the calculations,but the patient who takes the risk.Theodore Kocher(1841-1917,Swiss)a surgeon is a doctor who can operate and who knows when not to.烟台烟台.金海湾金海湾严严 琼琼(女女)经理经理刘国正刘国正(男男)经理经理鸣谢鸣谢宫廷门宫廷门