Swindle Peter, Eastham James A, Ohori Makoto, Kattan Michael W, Wheeler Thomas, Maru Norio, Slawin Kevin, Scardino Peter T
Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Urol. 2008 May;179(5 Suppl):S47-51. doi: 10.1016/j.juro.2008.03.137.
The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy.
We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate.
Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16).
We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.
根治性前列腺切除术（RP）标本中手术切缘阳性（PSM）的预后意义仍不明确。虽然大多数研究得出结论认为PSM是一个独立的不良预后因素，但其他研究报告称手术切缘状态对预后没有影响。这些不一致结论的一个原因是接受辅助治疗的PSM患者数量不同，以及用于解释辅助治疗时间进程对复发影响的统计方法不同。我们使用多种分析方法评估PSM的预后意义，同时考虑接受辅助治疗的患者。
我们分析了1983年至2000年由2名外科医生治疗的1389例连续临床分期为T1 - 3期前列腺癌患者。在179例PSM患者中，37例接受了辅助治疗（AT），29例接受放射治疗，8例接受激素治疗。由于用于解释接受AT男性的方法会影响分析结果，因此使用Cox比例风险技术对数据进行分析，采用5种方法考虑接受AT的患者：1）排除法；2）纳入法（忽略AT）；3）在AT时进行截尾；4）在AT时失败；5）将AT视为时间依赖性协变量。
总体而言，179例患者（12.9%）存在PSM，其中847例pT2期患者中有6.8%，522例pT3期患者中有23%。使用方法1、3、4和5分析时，PSM是癌症复发的显著预测因素（p分别为0.005、0.014、0.0005、0.002）。然而，使用忽略AT的方法2时，它不是复发的预测因素（p = 0.283）。使用方法5进行多变量分析表明，PSM（p = 0.002）是10年无进展概率（PFP）的独立预测因素，同时还有 Gleason评分（p = 0.0005）、包膜外侵犯（p = 0.0005）、精囊侵犯（p <0.0005）、阳性淋巴结（p <0.0005）和术前血清前列腺特异性抗原（p <0.0001）。使用方法5时，有和无PSM的患者10年PFP分别为58%±12%和81%±3%（p <0.00005）。使用方法5时，有PSM男性复发的相对风险为1.52（95%置信区间1.06 - 2.16）。
我们证实，在使用多种统计方法考虑接受AT患者的多变量分析中，PSM对RP后的PFP有显著的不利影响。虽然前列腺癌筛查策略已使大多数男性在RP时患有局限性疾病，但外科医生应继续努力降低手术切缘阳性率，以改善癌症控制结果。
