Moris Lisa, Van den Broeck Thomas, Tosco Lorenzo, Van Baelen Anthony, Gontero Paolo, Karnes Robert Jeffrey, Everaerts Wouter, Albersen Maarten, Bastian Patrick J, Chlosta Piotr, Claessens Frank, Chun Felix K, Graefen Markus, Gratzke Christian, Kneitz Burkhard, Marchioro Giansilvio, Salas Rafael Sanchez, Tombal Bertrand, Van Der Poel Henk, Walz Jochen Christoph, De Meerleer Gert, Bossi Alberto, Haustermans Karin, Montorsi Francesco, Van Poppel Hendrik, Spahn Martin, Briganti Alberto, Joniau Steven
Department of Development and Regeneration, Urology, University Hospitals Leuven, Leuven, Belgium; Laboratory of Molecular Endocrinology, KULeuven, Leuven, Belgium.
Department of Development and Regeneration, Urology, University Hospitals Leuven, Leuven, Belgium; Nuclear Medicine and Molecular Imaging, KULeuven, Leuven, Belgium.
Front Surg. 2016 Dec 16;3:65. doi: 10.3389/fsurg.2016.00065. eCollection 2016.
To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP).
In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD.
Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% ( = 671). Final Gleason score (GS) was 2-6 in 12.7% ( = 158), 7 in 52% ( = 649), and 8-10 in 35.4% ( = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% ( < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS.
Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.
确定淋巴结侵犯范围（LNI）对根治性前列腺切除术（RP）后长期肿瘤学结局的影响。
在这项回顾性研究中，我们检查了1989年至2011年间在八家不同的三级医疗机构接受RP和盆腔淋巴结清扫术（PLND）的1249例高危、非转移性前列腺癌患者的数据。我们拟合单变量和多变量Cox模型以评估癌症特异性生存（CSS）和总生存（OS）的独立预测因素。根据预测CSS的最具信息性的临界值将阳性淋巴结（LN）数量进行二分法分类。Kaplan-Meier曲线评估CSS和OS率。仅纳入在PLND时至少切除10个LN的患者。选择该临界值作为良好PLND的替代指标。
平均年龄为65岁（中位数：66岁，四分位间距60 - 70岁）。53.7%（n = 671）存在手术切缘阳性。最终Gleason评分（GS）为2 - 6分的占12.7%（n = 158），7分的占52%（n = 649），8 - 10分的占35.4%（n = 442）。PLND期间切除的LN中位数为15个（四分位间距12 - 17个）。在所有患者中，1128例（90.3%）有0 - 3个阳性LN，而126例（9.7%）有≥4个阳性LN。在10年随访中，0 - 3个阳性LN的患者与≥4个阳性LN的患者相比，CSS结局显著更好（87%对50%；P < 0.0001）。OS也得到了类似结果，0 - 3个阳性LN的患者与≥4个阳性LN的患者在10年时的生存率分别为72%对37%（P < 0.0001）。在多变量分析中，最终GS为8 - 10分、挽救性雄激素剥夺治疗以及≥4个（对<4个）阳性LN是CSS和OS较差的预测因素。病理分期pT4是CSS较差的额外预测因素。
四个或更多阳性LN、病理分期pT4以及最终GS为8 - 10分是高危前列腺癌患者CSS较差的独立预测因素。原发性肿瘤生物学仍然是肿瘤进展的主要驱动因素，≥4个阳性LN的患者可被视为一个富集的患者群体，应在其中研究新的治疗策略。
