Risk prediction models for biochemical recurrence after radical prostatectomy using prostate-specific antigen and Gleason score
Xin-HaiHuHenningCammannHellmuth-AMeyerKlaus KlausJungHong-BiaoLu LuNatalia NataliaLevasAhmedMagheliCarsten CarstenStephan StephanJonásBüsch
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Abstract:
为预言前列腺癌症的风险的许多计算机模型被开发了为生物化学的复发(BCR ) 的预言包括。然而，在一个 BCR 免费时期是稀罕的以后，在单个时间点为单个 BCR 免费概率当模特儿。从经历了 laparoscopic 激进分子前列腺切除术( LRP )的 1656 个病人的后续数据被用来模型使用开发一个人工的神经网络( ANN )预言 BCR 并且把它与逻辑回归( LR )作比较临床、病理学的参数，前列腺特定的抗原( PSA )，边缘地位( R0/1 )，病理学的阶段(磅)，和格利森分数( GS )。为在在操作，另外的 ANN，和 LR 以后的任何给定的时间的单个 BCR 预言，模型每 6 个月被计算多达 7.5 年后续。在为 ANN (0.754 ) 和 LR 的操作特征(巨鸟) 曲线(AUC ) 建模的接收装置(0.755 ) 下面的区域计算了立即后面的 LRP，为 GS 比那大(AUC：0.715；P = 0.0015 和 0.001 ) ，磅或 PSA (AUC：0.619；P 总是 <； 0.0001 ) 独自一个。GS 比 PSA 更好预言了 BCR (P = 0.0001 ) ，但是 ANN 和 LR 模型之间没有差别(P = 0.39 ) 。我们的 ANN 和 LR 模型从激进的前列腺切除术预言了单个 BCR 风险多达 10 年手术后。ANN 和 LR 模型同等地并且显著地独自与 PSA 和 GS 相比改进了 BCR 的预言。当 GS 和 ANN 产量价值被联合时，更精确的 BCR 预言是可能的，特别在有 GS ≥ 的高风险的病人； 7。Keywords:
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Several studies have revealed that the preoperative serum testosterone and percent tumor volume (PTV) predict extra-prostatic extension (EPE) and biochemical recurrence (BCR) after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy (LRP). We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen (PSA) >0.2 ng ml-1 . The threshold for serum total testosterone was 3.0 ng ml-1 . Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone (<3.0 ng ml-1 ) was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone (<3.0 ng ml-1 , adjusted OR, 8.52; 95% CI, 5.04-14.4, P= 0.001) predicted EPE and PTV (adjusted OR, 1.02; 95% CI, 1.01-1.05, P= 0.046) predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.
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To evaluate the association between tertiary Gleason pattern 5 (TGP5) and biochemical recurrence (BCR) in patients with prostate cancer (PCa) with a Gleason score (GS) of 7 after radical prostatectomy (RP).This retrospective study identified 350 patients who received RP and were graded as GS 7 (3+4 or 4+3) at the West China Hospital from January 2009 to December 2017. Initially, the patients were divided into two groups, TGP5 absence and TGP5 presence, independent of Gleason score. We further stratified the patients by adding the Gleason score into four groups: GS 3+4, GS 3+4/TGP5, GS 4+3, and GS 4+3/TGP5. Cox proportional-hazards models were used to evaluate the association between the status of TGP5 and BCR after adjusting for the confounding factors.The risk of BCR was significantly higher in patients with TGP5 when compared to patients without TGP5 (P=0.04, HR=2.17 95%, Cl: 1.03-4.59). For patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3 (P=0.04, HR=2.45, 95% Cl: 1.04-5.76).The TGP5 in patients with GS 7 had strong association with the risk of BCR and was an independent predictor for BCR. Further research on larger data sets is needed to confirm these findings.
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Nomogram
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The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer.The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA) < 20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR.The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population.This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram.
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The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages
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This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence (BCR) in patients with intermediate-risk prostate cancer (IRPCa). Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy (RARP) for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score ≤6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan–Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients (18.7%) had favorable pathology after RARP. Lower quartile prostate-specific antigen density (PSAD) was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score (odds ratio, 5.42; 95% confidence interval, 1.01–28.97; P = 0.048). During a median 37.8 (interquartile range, 24.6–60.2) months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles (log rank, P = 0.003). Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP (hazard ratio, 4.641; 95% confidence interval, 1.109–19.417; P = 0.036). The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.
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Men with pathologic evidence of seminal vesicle invasion (SVI) at radical prostatectomy (RP) have higher rates of biochemical recurrence (BCR) and mortality. Adjuvant radiotherapy (XRT) has been shown to increase freedom from BCR, but its impact on overall survival is controversial and it may represent overtreatment for some. The present study, therefore, sought to identify men with SVI at higher risk for BCR after RP in the absence of adjuvant XRT.We identified 180 patients in our institutional database who underwent RP from 1990 to 2011 who had pT3bN0-1 disease. The Kaplan-Meier method was used to estimate freedom from BCR for the overall cohort and substratified by Gleason score, PSA, surgical margin status, and lymph node positivity. Cox Proportional Hazards models were used to determine demographic and histopathological factors predictive of BCR. Time-dependent ROC curve analysis was conducted to assess the ability of the UCSF-CAPRA score to predict BCR.Median age was 64 years, and 52.8% of patients were preoperative D'Amico high risk. At RP, 41.4% had a positive surgical margin (PSM), and 12.2% had positive lymph nodes (LN). The most common sites of PSM were the peripheral zone (56.8%) and the apex (32.4%). Positive bladder neck margin (HR = 7.01, P = 0.035) and PSA 10-20 versus ≤10 (HR = 1.63, P = 0.047) predicted higher BCR in multivariable analyses. Median follow-up was 26 months, and 2-, 3-, and 5-year BCR-free rates were 56.1%, 49.0%, and 39.5%. Log rank tests showed that freedom from BCR was significantly less for Gleason 9-10, PSA >20, PSM, and N1 patients. The area under curve (AUC) for CAPRA in predicting BCR was 0.713 at 2 years, 0.692 at 3 years, and 0.641 at 5 years. Increasing CAPRA score was associated with an increased risk of BCR (HR = 1.33, P < 0.001).pT3b prostate cancer is a heterogeneous disease commonly associated with several high-risk features. Stratifying men with SVI by prognostic features (i.e., Gleason, PSA, node status, surgical margin status) and using these features to augment the CAPRA score will improve identification of those at higher risk for BCR that should be strongly considered for adjuvant XRT.
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The hypersensitive prostate specific antigen (PSA) test can measure in 0.01 ng/mL units, and its efficacy for screening after radical prostatectomy (RP) has been reported. In this study, we assessed patients who underwent RP to evaluate whether the nadir value affects biochemical recurrence (BCR). From 1995 to 2014, patients classified as N0 who had negative resection margins and a nadir PSA of less than 0.2 ng/mL were evaluated. The characteristics, pathological outcomes, PSA after RP, and BCR were assessed. A total of 1483 patients were enrolled. Among them, 323 (21.78%) patients showed BCR after RP. The mean age of the BCR group was 63.86±7.31 years, and while that of the no-recurrence group was 64.06±6.82 years ( P = 0.645). The mean preoperative PSA of the BCR group was 9.75±6.92 ng/mL and that of the no-recurrence group was 6.71±5.19 ng/mL ( P < 0.001). The mean time to nadir (TTN) in the BCR group was 4.64±7.65 months, while that in the no-recurrence group was 7.43±12.46 months ( P < 0.001). The mean PSA nadir value was 0.035±0.034 ng/mL in the BCR group and 0.014±0.009 ng/mL in the no-recurrence group ( P < 0.001). In multivariable Cox regression analyses, Gleason score, positive biopsy core percentages, minimal invasive surgery, nadir PSA value, and TTN were independently associated with BCR. The mean BCR occurred at 48.23±2.01 months after RP, and there was a significant difference in BCR occurrence according to the nadir PSA value ( P < 0.001). A high PSA nadir value and short TTN may predict the risk of BCR after successful RP, aiding the identification of candidates for adjuvant or salvage therapies after RP.
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