Analysis of expanded criteria to select candidates for active surveillance of low-risk prostate cancer

We aimed to analyze the value of each criterion for clinically insignificant prostate cancer (PCa) in the selection of men for active surveillance (AS) of low-risk PCa. We identified 532 men who were treated with radical prostatectomy from 2006 to 2013 who met 4 or all 5 of the criteria for clinically insignificant PCa (clinical stage ≤ T1, prostate specific antigen [PSA] density ≤ 0.15, biopsy Gleason score ≤ 6, number of positive biopsy cores ≤ 2, and no core with > 50% involvement) and analyzed their pathologic and biochemical outcomes. Patients who met all 5 criteria for clinically insignificant PCa were designated as group A (n = 172), and those who met 4 of 5 criteria were designated as group B (n = 360). The association of each criterion with adverse pathologic features was assessed via logistic regression analyses. Comparison of group A and B and also logistic regression analyses showed that PSA density > 0.15 ng ml⁻¹ and high (≥7) biopsy Gleason score were associated with adverse pathologic features. Higher (> T1c) clinical stage was not associated with any adverse pathologic features. Although ≤ 3 positive cores were not associated with any adverse pathology, ≥4 positive cores were associated with higher risk of extracapsular extension. Among potential candidates for AS, PSA density > 0.15 ng ml⁻¹ and biopsy Gleason score > 6 pose significantly higher risks of harboring more aggressive disease. The eligibility criteria for AS may be expanded to include men with clinical stage T2 tumor and 3 positive cores.     

Predictors of overall and cancer-free survival of patients with localized prostate cancer treated with primary androgen suppression therapy: results from the prostate cancer outcomes study

PURPOSE: Primary androgen suppression therapy for clinically localized prostate cancer is increasingly common in the United States despite a lack of supportive evidence for its use. We determined which demographic and clinical factors predict overall and cancer specific survival with this treatment strategy in patients enrolled in the Prostate Cancer Outcomes Study. MATERIALS AND METHODS: In 1994 to 1995 the Prostate Cancer Outcomes Study recruited 3,533 men diagnosed with prostate cancer. Clinical and treatment information was abstracted from medical records and demographic characteristics were obtained from patient surveys 6, 12, 24 and 60 months after diagnosis. Overall and cancer specific mortality was analyzed through December 2002 using the Kaplan-Meier method and Cox regression. RESULTS: A total of 276 patients had organ confined (cT1-2) prostatic adenocarcinoma and received primary androgen suppression therapy within 1 year of diagnosis. Median followup for censored patients was 7.6 years (range 1.1 to 8.1). Five-year overall and cancer specific survival was 66% (95% CI 59-72) and 91% (95% CI 86-94), respectively. Independent predictors of shorter overall survival were patient age 75 years or older, prostate specific antigen 20 ng/ml or greater, Gleason score 7 or greater and abnormal digital rectal examination. Gleason score 7 or greater, prostate specific antigen 20 ng/ml or greater and a low comorbidity index were independent predictors of shorter cancer specific survival. CONCLUSIONS: The use of primary androgen suppression therapy in the Prostate Cancer Outcomes Study data set resulted in 91% 5-year cancer specific survival. Advanced age, and factors that reflect tumor burden and biology were predictive of overall survival, while cancer specific survival was predicted by tumor factors and the burden of comorbid conditions. A nomogram for predicting overall survival at 5 years was constructed.     

A post‐radical‐prostatectomy nomogram incorporating new pathological variables and interaction terms for improved prognosis

Study Type – Prognosis (systematic review)
Level of Evidence 2a What’s known on the subject? and What does the study add? Nomograms are commonly used by urologists to assess a patient’s risk of developing biochemical failure (PSA recurrence) after radical prostatectomy. The nomograms currently available on websites and in the published literature do not take into account recent developments in pathological reporting which may improve our ability to more accurately predict patient prognosis. Furthermore, currently available nomograms treat all clinical predictors as independent variables without considering the possibility that these factors may be interlinked, which may alter their predictive value. Our study assesses the predictive value of several new pathological variables and demonstrates that the per cent of Gleason patterns 4 and/or 5 (% 4/5), intraductal prostatic carcinoma and prostate weight significantly improve the predictive value of a model based on established pathological variables. We also show that consideration of interactions between % 4/5, surgical margin status and extracapsular extension further improves our accuracy in predicting patient PSA recurrence. Finally, we find that published nomograms based on PSA recurrence defined as ≥0.4 ng/mL provide over‐optimistic predictions for prostate cancer patients where PSA recurrence was defined as ≥0.2 ng/mL.

OBJECTIVE

• ? To evaluate new variables in prostate pathology reporting including, the per cent of Gleason patterns 4 and/or 5 (% 4/5), presence or absence of intraductal carcinoma of the prostate (IDCP), tumour volume and the prostatic zone of tumour origin as predictors of post‐radical‐prostatectomy (RP) biochemical recurrence (BCR).
• ? To develop an optimal postoperative nomogram for patients with prostate cancer.

PATIENTS AND METHODS

• ? Our study cohort was 1939 eligible patients from the Abbott West Australian Prostatectomy Database.
• ? Multivariate Cox proportional hazard regression models were developed to predict BCR which was defined as prostate‐specific antigen (PSA) ≥0.2 ng/mL.
• ? Our models and the 2009 Kattan postoperative nomogram were compared in terms of discrimination and calibration, with internal validation of our final model performed using bootstrapping methods. Our final model is presented as a nomogram.

RESULTS

• ? The Kattan nomogram was accurate in discriminating our patients according to risk (concordance index: 0.791) but calibration analysis indicated underestimation of patient risk, particularly for high‐risk disease.
• ? Our nomogram incorporates % 4/5, IDCP and prostate weight plus interaction terms between % 4/5, positive surgical margins and extracapsular extension, giving improved predictive accuracy (concordance index: 0.828) and calibration.

CONCLUSIONS

• ? Nomograms that predict risk of BCR defined as PSA ≥0.4 ng/mL may not be optimal for patient cohorts where BCR is defined as PSA ≥0.2 ng/mL.
• ? If our findings are validated in other populations, current post‐RP nomograms may be improved to a modest degree by incorporating the new variables prostate weight, IDCP and % 4/5, and by considering interactions between predictive variables.

     

Nomograms to predict the pathological stage of clinically localized prostate cancer in Korean men: Comparison with Western predictive tools using decision curve analysis

Objectives: To develop and evaluate nomograms to predict the pathological stage of clinically localized prostate cancer after radical prostatectomy in Korean men. Methods: We reviewed the medical records of 2041 patients who had clinical stages T1c–T3a prostate cancer and were treated solely with radical prostatectomy at two hospitals. Logistic regressions were carried out to predict organ‐confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis using preoperative variables and resulting nomograms. Internal validations were assessed using the area under the receiver operating characteristic curve and calibration plot, and then external validations were carried out on 129 patients from another hospital. Head‐to‐head comparisons with 2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried out using the area under the curve and decision curve analysis. Results: The significant predictors for organ‐confined disease and extraprostatic extension were clinical stage, prostate‐specific antigen, Gleason score and a percent positive core of biopsy. Significant predictors for seminal vesicle invasion were prostate‐specific antigen, Gleason score and percent positive core, and those for lymph node metastasis were prostate‐specific antigen and percent positive core. The area under the curve of established nomograms for organ‐confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were 0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated and externally validated. These nomograms showed significantly higher accuracies and net benefits than two Western tools in Korean men. Conclusion: This is the first study to have developed and fully validated nomograms to predict the pathological stage of prostate cancer in an Asian population. These nomograms might be more accurate and useful for Korean men than other predictive models developed using Western populations.     

Treatment of patients with high risk localized prostate cancer: results from cancer of the prostate strategic urological research endeavor (CaPSURE)

PURPOSE: Pretreatment risk assessment models facilitate more appropriate selection of treatment for prostate cancer. However, men with high risk disease remain a challenge with significant potential for primary treatment failure. We characterize patterns of treatment for high risk prostate cancer in a community based cohort. MATERIALS AND METHODS: In the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, a longitudinal disease registry of men with prostate cancer, we identified those with nonmetastatic, high risk disease based on T stage, tumor grade and serum prostate specific antigen (PSA). Differences in primary treatment, and the use of neoadjuvant and adjuvant therapy in patients at low, intermediate and high risk were assessed. In the high risk cohort predictors of the type of primary treatment, and the use of neoadjuvant and adjuvant androgen therapy were identified. RESULTS: Of the cancers 34%, 40% and 26% were low, intermediate and high risk, respectively. Differences in primary treatment type among the 3 risk groups were statistically significant (p <0.0001) with increasing external beam radiation therapy and androgen deprivation, and decreased surgery, brachytherapy and surveillance in men with high risk cancers. In this group older age, higher PSA and nonprivate insurance were associated with decreased use of radical prostatectomy. More than half of the men at high risk receiving radiation therapy also received androgen deprivation, which was significantly higher than in the low and intermediate risk groups (p <0.0001). Factors associated with androgen deprivation in high risk disease were primary therapy, PSA, Gleason sum, T stage, body mass index, insurance status and ethnicity. PSA and Gleason sum were the primary determinants of adjuvant radiation after prostatectomy. CONCLUSIONS: Men with high risk but nonmetastatic prostate cancer are more likely to receive radiation therapy as well as androgen deprivation with the latter as primary therapy or in conjunction with local treatment. These data stress the importance of pretreatment risk stratification, education regarding appropriate combinations of local and systemic therapies, and the consideration of novel clinical trials in patients at higher risk.     

A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy

PURPOSE: Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS: Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. RESULTS: On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. CONCLUSIONS: Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy.     

Comparison of accuracy between the Partin tables of 1997 and 2001 to predict final pathological stage in clinically localized prostate cancer

PURPOSE: We validated externally the predictive accuracy of the 2001 Partin tables and compared the 1997 and 2001 versions. MATERIALS AND METHODS: We used ROC derived AUC to test the predictive accuracy of organ confinement (OC), extraprostatic extension (ECE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) of 1997 and 2001 Partin tables derived probabilities. These probabilities were defined by the pretreatment clinical stage, serum prostate specific antigen and biopsy Gleason grade of 2,139 patients treated with radical prostatectomy for clinically localized prostate cancer. RESULTS: OC, ECE, SVI and LNI were noted in 63.5%, 23.1%, 10.5% and 2.9% of cases, respectively. AUC of the 2001 tables was 0.787, 0.766, 0.775 and 0.790, for OC, ECE, SVI and LNI, respectively. These values were virtually the same as the respective 1997 Partin table AUC values, namely 0.784, 0.728, 0.791 and 0.799. CONCLUSIONS: This external validation of the 2001 Partin tables confirms good predictive accuracy of the updated tables. However, predictive accuracy in this external validation data set of 2,139 European men is virtually the same as that of the original 1997 tables. Therefore, a transition from the 1997 tables to the updated 2001 version does not appear warranted unless superior accuracy is demonstrated in other external cohorts.     

Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram

PURPOSE: Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history. Statistical models have been proposed to predict indolent cancer. We validated and updated model predictions for a screening setting. MATERIALS AND METHODS: We selected 247 patients with clinical stage T1C or T2A from the European Randomized Study on Screening for Prostate Cancer who were treated with radical prostatectomy. We validated a nomogram that had previously been developed in a clinical setting. Predictive characteristics were serum prostate specific antigen, ultrasound prostate volume, clinical stage, prostate biopsy Gleason grade, and total length of cancer and noncancer tissue in biopsy cores. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements. Logistic regression was used to update the previous model and examine the contribution of other potential predictors. RESULTS: Overall 121 of 247 patients (49%) had indolent cancer, while the average predicted probability was around 20% (p <0.001). Effects of individual variables were similar to those found before and discriminative ability was adequate (AUC 0.76). An updated model was constructed, which merely recalibrated the nomogram and did not apply additional predictors. CONCLUSIONS: Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram. However, an updated model can support patients and clinicians when the various treatment options for prostate cancer are considered.