A single-center study on predicting outcomes of primary androgen deprivation therapy for prostate cancer using the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score.

OBJECTIVE: Japan Cancer of the Prostate Risk Assessment scores are reportedly useful for predicting progression-free survival after primary androgen deprivation therapy of prostate cancer patients. This study validated the risk assessment at a single institution. METHODS: We studied 255 prostate cancer patients given primary androgen deprivation therapy. Progression-free survival, cause-specific survival and overall survival were analyzed according to Japan Cancer of the Prostate Risk Assessment score-based risk classification. Cases with lymph node or distant metastases were subdivided by the risk classification. RESULTS: Ages ranged from 50 to 90 years (median: 76.5). Observation periods were 2-199 (median: 46.5) months. Primary androgen deprivation therapy includes combined androgen blockade in 150 cases (58.8%), uncombined luteinizing hormone-releasing hormone agonist in 97 (38.0%) and uncombined anti-androgenic agent in 8 (3.2%). Risk classified by Japan Cancer of the Prostate Risk Assessment scores was low in 104 cases (40.8%), intermediate in 86 (33.7%) and high in 65 (25.5%). The 5-year/10-year progression-free survival rates were 100%/80.8% in the low-risk, 82.3%/69.5% in the intermediate-risk and 34.7%/16.5% in the high-risk group. The 5-year/10-year cause-specific survival rates were 100%/100% in the low-risk, 90.7%/58.2% in the intermediate-risk and 63%/30.8% in the high-risk group. The 5-year/10-year overall survival rates were 87.5%/78.5% in the low-risk, 76.2%/43.1% in the intermediate-risk and 54.9%/25.4% in the high-risk group. For lymph node metastasis, cause-specific survival differed minimally between the intermediate- and high-risk groups (P = 0.1118). For distant metastasis, cause-specific survival differed significantly between the intermediate- and high-risk groups (P = 0.0264). CONCLUSIONS: Japan Cancer of the Prostate Risk Assessment score-based risk classification is useful for predicting post-primary androgen deprivation therapy progression-free survival, cause-specific survival and overall survival. Subtyping patients based on Japan Cancer of the Prostate Risk Assessment scores is particularly useful for predicting cause-specific survival with distant metastasis from prostate cancer.

The CAPRA score versus sub-types of minimal residual disease to predict biochemical failure after external beam radiotherapy.

INTRODUCTION: External beam radiotherapy is a treatment option for clinically localised prostate cancer; however, some 15% of patients will undergo treatment failure within 5 years. The objective was to compare the Cancer of the Prostate Risk Assessment (CAPRA) score (based on the clinical-pathological findings) and the sub-types of minimal residual disease (MRD) (based on the biological properties of the cancer cells) risk classifications to predict biochemical failure (BF) after external beam radiotherapy. METHODS AND PATIENTS: Clinical-pathological findings were obtained from the prostate biopsy to determine the CAPRA score and used to define low-, intermediate- and high-risk patients. Blood and bone marrow were obtained 3 months after radiotherapy; circulating prostate cells (CPCs) and micro-metastasis were detected using immunocytochemistry with anti-prostate specific antigen. CPCs and micro-metastasis were classified as positive if at least one cell was detected in the sample. Three subgroups were formed Group A (MRD negative), Group B (micro-metastasis positive, CPC negative) and Group C (CPC positive)Patients were followed up for 10 years or until biochemical failure. Biochemical failure free survival (BFFS) curves were constructed using Kaplan-Meier (observed), a flexible parameter model (predicted survival) and the restricted mean survival time (RMST) was calculated for each sub-group. RESULTS: 309 men participated with a median follow-up of 8 years. The risk of biochemical failure increased proportionally with increasing CAPRA score, hazard ratio 1.18 for intermediate and 1.69 for high risk patients. After 10 years, the percentage BFFS and RMST to failure were 74%, 49%, 16% and 9, 7 and 6 years, respectively. The agreement between observed and predicted BFFS was acceptable (Harrell´s C 0.62). The BFFS curves for MRD were different and not proportional, survival curves for men MRD negative and only micro-metastasis were similar up to 5 years, and then there was increasing failure in the micro-metastasis only group. After 10 years, the percentage BFFS and RMST to failure were 95%, 59%, 28% and 10, 9 and 6 years, respectively. The CAPRA score failed to distinguish between Groups A and B, one third of high risk Group C had low risk CAPRA scores. The agreement between observed and predicted BFFS was very good (Harrell´s C 0.92). Minimal residual disease hazard ratios were Group B 1.84 and Group C 4.51. CONCLUSIONS: The MRD prognostic classification is based on the biological characteristics of the tumour cell-microenvironment interaction, to give three groups, MRD negative, only bone marrow micro-metastasis and CPC positive prostate cancer. Differing from the CAPRA score classification the risk of treatment failure changes with time, differentiating between early and late treatment failures and incorporates the concept of dormancy. It proved to be superior to the CAPRA score in predicting biochemical failure and the results need to be confirmed in larger studies.

The Incremental Role of Magnetic Resonance Imaging for Prostate Cancer Staging before Radical Prostatectomy.

In the present report we aimed to analyze the incremental value of preoperative magnetic resonance imaging (MRI), in addition to clinical variables and clinically-derived nomograms, in predicting outcomes radical prostatectomy (RP). All Mayo Clinic RP patients who underwent preoperative 1.5-Tesla MRI with endo-rectal coil from 2003 to 2013 were identified. Clinical and histopathological variables were used to calculate Partin estimates and Cancer of the Prostate Risk Assessment (CAPRA) score. MRI results in terms of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph-node invasion (N+) were recorded. Using RP pathology as gold standard, we developed multivariate logistic regression models based on clinical variables, Partin Tables, and CAPRA score, and assessed their predictive accuracy before and after the addition of MRI results. Five hundred and one patients were included. MRI + clinical models outperformed clinical-based models alone for all outcomes. Comparing Partin and Partin + MRI predictive models, the areas under the curve were 0.61 versus 0.73 for ECE, 0.75 versus 0.82 for SVI, and 0.82 versus 0.85 for N+. Comparing CAPRA and CAPRA + MRI models, the areas under the curve were 0.69 versus 0.77 for ECE, 0.75 versus 0.83 for SVI, and 0.82 versus 0.85 for N+. Our data show that MRI can improve clinical-based models in prediction of nonorgan confined disease, particularly for ECE and SVI. PATIENT SUMMARY: Magnetic resonance imaging, together with clinical information, can be useful in preoperative assessment before radical prostatectomy.

Limited improvement of incorporating primary circulating prostate cells with the CAPRA score to predict biochemical failure-free outcome of radical prostatectomy for prostate cancer.

OBJECTIVE: To establish a prediction model for early biochemical failure based on the Cancer of the Prostate Risk Assessment (CAPRA) score, the presence or absence of primary circulating prostate cells (CPC) and the number of primary CPC (nCPC)/8ml blood sample is detected before surgery. PATIENTS AND METHODS: A prospective single-center study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinical-pathological findings were used to calculate the CAPRA score. Before surgery blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen and P504S, and the presence or absence of CPCs and the number of cells detected/8ml blood sample was registered. Patients were followed up for up to 5 years; biochemical failure was defined as a prostate-specific antigen>0.2ng/ml. The validity of the CAPRA score was calibrated using partial validation, and the fractional polynomial Cox proportional hazard regression was used to build 3 models, which underwent a decision analysis curve to determine the predictive value of the 3 models with respect to biochemical failure. RESULTS: A total of 267 men participated, mean age 65.80 years, and after 5 years of follow-up the biochemical-free survival was 67.42%. The model using CAPRA score showed a hazards ratio (HR) of 5.76 between low and high-risk groups, that of CPC with a HR of 26.84 between positive and negative groups, and the combined model showed a HR of 4.16 for CAPRA score and 19.93 for CPC. Using the continuous variable nCPC, there was no improvement in the predictive value of the model compared with the model using a positive-negative result of CPC detection. The combined CAPRA-nCPC model showed an improvement of the predictive performance for biochemical failure using the Harrell׳s C concordance test and a net benefit on DCA in comparison with either model used separately. The use of primary CPC as a predictive factor based on their presence or absence did not predict aggressive disease or biochemical failure. CONCLUSION: Although the use of a combined CAPRA-nCPC model improves the prediction of biochemical failure in patients undergoing radical prostatectomy for prostate cancer, this is minimal. The use of the presence or absence of primary CPCs alone did not predict aggressive disease or biochemical failure.

A novel DNA methylation score accurately predicts death from prostate cancer in men with low to intermediate clinical risk factors.

Clinically aggressive disease behavior is difficult to predict in men with low to intermediate clinical risk prostate cancer and methylation biomarkers may be a valuable adjunct for assessing the management of these patients. We set to evaluate the utility of DNA methylation to identify high risk disease in men currently considered as low or intermediate risk. DNA was extracted from formalin-fixed paraffin-embedded transurethral prostate resection tissues collected during the years 1990-96 in a watchful-waiting cohort of men in the UK. The primary end point was death of prostate cancer, assessed by reviewing cancer registry records from 2009. Methylation was quantified by pyrosequencing assays for six genes (HSPB1, CCND2, TIG1, DPYS, PITX2, and MAL) with established biomarker value in prostate cancer. A novel prognostic methylation score was developed by multivariate Cox modelling using the six methylation biomarkers in 385 men with low-and-intermediate clinical risk variables and its prognostic value compared to two previously defined clinically-derived risk scores. Methylation score was the most significant variable in univariate and bivariate analysis in men with low-to-intermediate CAPRA risk score. When combined with CAPRA score the hazard ratio was 2.02; 95% confidence interval, 1.40-2.92. For a methylation score sensitivity of 83% the specificity was 44%, while the maximum achieved sensitivity by CAPRA was 68% at a specificity of 44%. The derived methylation score is a strong predictor of aggressive prostate cancer that could have an important role in directing the management of patients with low-to-intermediate risk disease. The estimated areas under the curve (AUC) at 10 years of follow-up were 0.62 (95% CI: 0.51, 0.70) and 0.74 (95% CI: 0.65, 0.82) for CAPRA, and combined (CAPRA + methylation) risk score (CRS) respectively.