Kestin Larry L, Goldstein Neal S, Vicini Frank A, Martinez Alvaro A
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA.
J Urol. 2002 Nov;168(5):1994-9. doi: 10.1016/S0022-5347(05)64280-2.
The clinical significance of pretreatment biopsy characteristics is not well understood relative to known prognostic factors. We performed a complete pathology analysis of pretreatment biopsy specimens in an attempt to clarify their impact on clinical outcome following radiotherapy.
From 1991 to 1999, 160 patients with locally advanced prostate cancer were prospectively treated with external beam radiotherapy in combination with high dose rate brachytherapy at our hospital and had pretreatment biopsy material available for complete pathological review. Patients with pretreatment prostate specific antigen (PSA) 10.0 ng./ml. or greater, Gleason 7 or greater or clinical stage T2b-T3c N0 M0 disease were eligible for study entry. Pelvic external beam radiotherapy (46.0 Gy.) was supplemented with 3 (1991 to 1995) or 2 (1995 to 1999) ultrasound guided transperineal interstitial iridium high dose rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy. per implant. All pretreatment biopsy specimen slides from each case were reviewed by a single pathologist (N. S. G.). Median followup was 4.2 years. Biochemical failure was defined as 3 consecutive PSA increases.
On univariate analysis pretreatment PSA, Gleason score, clinical T classification, percentage of positive biopsy cores, dose per implant and total radiotherapy dose (equivalent in 2 Gy. fractions) were significantly associated with biochemical failure. Perineural invasion was of borderline significance (p = 0.07). On univariate analysis for clinical failure only Gleason score and percent positive cores were significant. Percent positive cores was associated with biochemical and clinical failure whether analyzed in subgroups or as a continuous variable. Patients with less than 33% positive cores had a 5-year biochemical control rate of 83% and 5-year clinical failure rate of only 7%. Conversely, patients with more than 67% positive cores had a 5-year biochemical control rate of only 57% and 25% had clinical failure at 5 years. Since percent positive cores correlated with biochemical and clinical failure, an analysis was performed to determine which other prognostic factors were associated with percent positive cores. Pretreatment PSA level, Gleason score, clinical T classification and perineural invasion were significantly associated with a higher percent positive cores. Nevertheless, on Cox multiple regression analysis higher percent positive cores, pretreatment PSA and Gleason score remained independently associated with biochemical failure but not T classification. On Cox multiple regression analysis for clinical failure only Gleason score remained independently significant with percent positive cores maintaining borderline significance (p = 0.07).
Percent positive pretreatment biopsy cores is a powerful predictor of biochemical and clinical outcome for prostate cancer treated with radiotherapy, independent of other known prognostic factors. Percent positive cores should be seriously considered as a primary factor in risk group stratification for prostate cancer.
相对于已知的预后因素，预处理活检特征的临床意义尚未得到充分理解。我们对预处理活检标本进行了全面的病理分析，以阐明其对放疗后临床结局的影响。
1991年至1999年，我院对160例局部晚期前列腺癌患者进行了前瞻性的外照射放疗联合高剂量率近距离放疗，且有预处理活检材料可供进行完整的病理检查。预处理前列腺特异性抗原（PSA）≥10.0 ng/ml、Gleason评分≥7或临床分期为T2b - T3c N0 M0疾病的患者符合研究入组标准。盆腔外照射放疗（46.0 Gy）辅以3次（1991年至1995年）或2次（1995年至1999年）超声引导下经会阴间质铱高剂量率植入。近距离放疗剂量从每次植入5.50 Gy逐步增加至10.50 Gy。每个病例的所有预处理活检标本玻片均由一名病理学家（N.S.G.）进行复查。中位随访时间为4.2年。生化失败定义为PSA连续3次升高。
单因素分析显示，预处理PSA、Gleason评分、临床T分期、活检阳性核心百分比、每次植入剂量和总放疗剂量（等效于2 Gy分次剂量）与生化失败显著相关。神经周围侵犯具有临界显著性（p = 0.07）。仅对临床失败进行单因素分析时，只有Gleason评分和阳性核心百分比具有显著性。无论作为亚组分析还是作为连续变量分析，阳性核心百分比均与生化和临床失败相关。阳性核心少于33%的患者5年生化控制率为83%，5年临床失败率仅为7%。相反，阳性核心超过67%的患者5年生化控制率仅为57%，25%的患者在5年时出现临床失败。由于阳性核心百分比与生化和临床失败相关联，因此进行了一项分析以确定哪些其他预后因素与阳性核心百分比相关。预处理PSA水平、Gleason评分、临床T分期和神经周围侵犯与较高的阳性核心百分比显著相关。然而，在Cox多因素回归分析中，较高的阳性核心百分比、预处理PSA和Gleason评分仍然独立地与生化失败相关，但与T分期无关。在对临床失败进行的Cox多因素回归分析中，只有Gleason评分仍然独立显著，阳性核心百分比维持临界显著性（p = 0.07）。
预处理活检阳性核心百分比是放疗治疗前列腺癌生化和临床结局的有力预测指标，独立于其他已知的预后因素。阳性核心百分比应被认真视为前列腺癌风险分组分层的主要因素。
