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Background:The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score.Methods:Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort.Results:In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10−13) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10−6). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ2=89.0, P<10−20) and captured virtually all available prognostic information.Conclusions:The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment. [ABSTRACT FROM AUTHOR]

The prostate gland has among the highest level of polyamines in the body and prostate carcinomas have even greater elevated polyamine levels. These ubiquitous molecules synthesized by prostate epithelium are involved in many biochemical processes including cellular proliferation, cell cycle regulation, and protein synthesis. These properties have made polyamines a potential target for therapeutic intervention in diseases of excessive cell proliferation such as cancer. However, attempts to limit tumor growth by inhibition of polyamine synthesis have not been very successful since cells have the capacity to take up polyamines from the bloodstream. We report here studies utilizing polyamine depletion by means of a combination of blockade of polyamine synthesis with DFMO (α-difluoromethylornithine), an inhibitor of ornithine decarboxylase, the rate limiting enzyme in the polyamine synthetic pathway, and ORI 1202, a novel inhibitor of polyamine transport into the cell. This cytostatic combination, even in the presence of excess extracellular polyamines, significantly slowed the growth of the human tumor cell line PC-3 grown in tissue culture with an EC50 in the μM range. Other prostate cell lines were similarly growth inhibited including LNCaP.FGC and DU145. Growth of the PC-3 tumor cell line as a xenograft in nude mice was also slowed significantly by this combination of compounds. Polyamine levels in the tumor were lowered from control tumor levels. This combination therapy could provide an effective and potentially non-toxic therapy for prostate tumors.Prostate Cancer and Prostatic Diseases (2000) 3, 275–279 [ABSTRACT FROM AUTHOR]

PSA complexed with alpha-1-anti-chymotrypsin (cPSA™) is the moiety in greatest proportion in the serum of men with prostate cancer (CAP). The performance of this analyte has been established primarily in retrospective archival serum. Studies indicate cPSA™ provides the specificity enhancement of the free-to-total PSA ratio, yet obviates the need to measure two markers. In the present investigation we sought to establish the stability of cPSA™ with long-term storage. Serum from men undergoing ultrasound-guided biopsy was utilized. Serum was assayed soon after collection and 18 months later. All serum was initially aliquotted and stored at -80°C. There was no freeze–thaw. cPSA™ was measured utilizing the Bayer Immuno 1 method according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8) and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist between the two determinants (r2=1.0, slope=1.01, t-test P=0.9194). These data establish for the first time the long-term stability of cPSA™. Retrospective studies performed on archival material should give meaningful results. Prostate Cancer and Prostatic Diseases (2000) 3, 191–194 [ABSTRACT FROM AUTHOR]

Deals with presentations which covered different aspects of the epidemiology of and for screening prostate cancer. Discussion on the changing incidence and presentation of prostatic carcinoma; Incidence of prostate cancer among African-Americans; Update on the American Cancer Society Screening Project.

This session included five presentations in the areas of pathology of precursor lesions and carcinoma of the prostate, the value of determining neovascularity in the diagnosis and staging of prostate cancer, new ‘molecular’ markers, correlation between pre- and postoperative Gleason scores and a study dealing with transition zone PSA density. The abstracts and talks are summarized in the next few pages. [ABSTRACT FROM AUTHOR]

Prostate-specific antigen (PSA) is the most important of all tumor markers in that it has significant applications in all aspects of the management of men with prostatic disease. Certainly, the most important utilization of PSA is for the early detection of this most ubiquitous of all human neoplasms. This article reviews the salient features of PSA, with particular emphasis on strategies to improve its utility in the diagnosis of prostate cancer. So-called PSA derivatives--including age-specific PSA, PSA velocity, and PSA density--are discussed. With the recognition of molecular forms of PSA, however, the ratio of free-to-total PSA, and now the complex form of PSA, have been shown to be more specific indicators of the presence of malignancy. Significant public interest and research efforts in prostate cancer have resulted in numerous advances over the past decade. The discovery of PSA and the development of assays to measure it will undoubtedly be recorded as one of the most important advances in the management of men with prostate cancer. [ABSTRACT FROM AUTHOR]

Because prostate cancer has a long latency and high incidence, it is a good target for chemoprevention by agents such as retinoids, antiandrogens, antiestrogens, and vitamin D analogs. Phase II chemoprevention trials are frequently conducted on cohorts of patients with previous cancers or premalignant lesions who are scheduled for prostate cancer surgery; such trials are currently in progress with several agents. Prostatic intraepithelial neoplasia (PIN) can be used as a surrogate endpoint biomarker for prostate cancer incidence. Studies of men with high-grade PIN (HGPIN) are particularly useful in that they require a much smaller cohort of 200–400 patients instead of the 18 000 patients required for typical Phase III trials. Even with a smaller sample size, statistically significant evidence of cancer prevention is achieved due to the high probability of HGPIN progressing to cancer (35–55%). A Bayesian sequential monitoring system allows interim analysis of biomarker modulation as early as the completion of 30 patients. Putting all these strategies together will help inhibit, delay, or modulate the natural history of prostate carcinogenesis. [ABSTRACT FROM AUTHOR]

Prostate-specific antigen (PSA) has emerged as the most predictive test of whether or not a man has prostatic carcinoma. The free to total PSA ratio provides important enhancement in specificity, thus obviating unnecessary negative biopsies. In the absence of an international standard for total PSA, much less free PSA, variation between manufacturers may cause confusing results. We sought to compare three different manufacturer’s free and total PSA assays in a population consisting of consecutive patients who had PSA testing in a reference laboratory in Germany. Between April 1994 and July 1996, serum specimens from 240 men were evaluated with three different free and total PSA assays. Indications for PSA determination were based on the referring physician, who also provided the clinical diagnosis. Total and free PSA were measured on the same freeze–thaw cycle with Chiron Diagnostics, Enzymun Boehringer Mannheim, and Hybritech Tandem-R assays. Seventy-nine men had carcinoma of the prostate, 120 had clinical evidence of benign prostatic hyperplasia and 27 were without evidence of prostatic disease. The Chiron ACS: 180 free to total ratio compared very well with the Tandem-R assay at the 95% sensitivity level, affording 17 and 22% specificity respectively. Using the range of total PSA of 4–10 ng/ml, the increase in specificity of the free to total PSA is quite significant, and the specificity of the Enzymun assays is greatly improved. (Specificity of 49%, 29% and 25% at 95% sensitivity for ACS, Enzymun and Tandem respectively.) This data, based on ‘real world’ clinical experience, shows significant variation between different manufacturers’ assays. There was significant equivalence between the Chiron and Hybritech assays. The Enzymun assay performed well only when data from the total PSA range of 4–10 ng/ml was included. Clinicians must be aware of which manufacturers’ assays for both the free and total PSA... [ABSTRACT FROM AUTHOR]

Aims of the study: Retrospective studies investigating the use of percent free-PSA for early detection of prostate cancer were limited for various reasons: by their use of long-term stored sera, poor mix of non-cancer to cancer cases and the use of only men with PSA values between 4.0 and 10.0 ng/mL. This prospective study investigates the clinical utility of percent free-PSA and complexed-PSA for early detection of prostate cancer in 219 consecutive men presenting for prostate biopsy. Methods: Of 246 consecutive men who underwent ultrasound guided sextant biopsy of the prostate for PSA elevation and/or suspicious digital rectal exam, 219 men had serum total PSA levels between 2.0 and 20.0 ng/mL and were included in this study. Serum total, free and complexed (PSA–ACT) were measured (Hybritech Inc.). Results: Pathologic examinations demonstrated that 72% and 28% of the biopsies were non-cancer and cancer respectively. The mean percent free-PSA was statistically different between the groups (cancer 14%±6.4 and non-cancer 18±9%, P<0.001) and improved cancer detection. PSA–ACT provided only modest improvement in cancer detection over that of total PSA. Among this cohort of men, the optimal total PSA reflex range for percent free-PSA was 3.0–7.0 ng/mL (38% specificity) with a percent free-PSA cut-off of 20% (95% sensitivity) yet only affected 56% of the cases. Conclusions: PSA–ACT added very little additional value to the clinical utility of total PSA for early detection. Percent free-PSA performed well for all reflex ranges. A sensitivity and specificity of 95% and 20% respectively were obtained using a single cut-off of 25% for percent free-PSA for the group of men with total PSA values between 4.0 and 10.0 and correlated well with recently reported prospective analyses. [ABSTRACT FROM AUTHOR]

Due to the historically large number of patients with localized prostate cancer (CAP) treated by radiation therapy, an increasing number of patients are presenting local failure. The currently available concepts regarding its definition as well as management options are reviewed. The literature regarding radiation failure for localized prostate cancer was reviewed. Emphasis was made on articles concerning definition of radiation failure, patient evaluation and restaging and definitive as well as palliative management options. There is definitely a subset of patients with locally recurrent prostate cancer without evidence of metastasis that could potentially benefit from aggressive local therapy. A treatment algorithm is proposed but it should be emphasized that treatment options should be individualized to suit the need of a particular patient. [ABSTRACT FROM AUTHOR]

Context: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use.Objective: To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied.Design: Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif).Setting: Seven nationwide university medical centers.Participants: A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis.Main Outcome Measures: A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients.Results: The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL.Conclusions: Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice. [ABSTRACT FROM AUTHOR]

In this study we evaluated the physiological variation of free and total prostate-specific antigen (PSA) levels to determine how the percent free/total PSA was affected. Twenty four patients had blood drawn for ten consecutive weekdays. The percent coefficient of variation (%CV) of biological variation was calculated. The results were log-normally distributed with geometric means of 12.0% CV, 7.3% CV, and 8.8% CV for free, total, and percent free/total PSA, respectively. When applied, the percent free/total, PSA would need to fluctuate by 31% to indicate that a significant change (critical difference, P<0.05) between two measurements had occurred. Biological variation of PSA measurements is substantial. [ABSTRACT FROM AUTHOR]

All neoplasms require angiogenesis and resulting neovascularity for growth beyond 1 mm2. Quantitative microvessel density (MVD) has been shown to provide staging and prognostic significance in human prostate cancer (CaP). recently, it has been demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. There is also an increased expression of vascular endothelial growth factor which promotes neovascularization. p53 gene mutation and MVD were investigated in men with prostate cancer. Sections from 103 radical prostatectomy cases were evaluated with immunohistochemistry to detect mutant p53 proteins. Quantitative MVD was performed on the cases exhibiting p53 positive staining and compared with negative fields of similar Gleason grade on the same histologic sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 20 cases, the MVD in p53 positive areas was greater than corresponding control regions (overall P<0.0001). Extent of p53 abnormality, as well as MVD, correlated with pathologic stage. These data suggest that mutations of the p53 tumour suppressor gene may be associated with increased angiogenesis in CaP. In addition to providing staging and prognostic information, this relationship potentially has therapeutic implications. [ABSTRACT FROM AUTHOR]

Relates a personal viewpoint on the treatment of clinically localized prostatic carcinoma. Reasons for the problem in prostate cancer; Limitations of primary care practice; Account of a clinical experience.

Purpose: A 2-gene, urine based molecular test that combines mRNA biomarkers with clinical factors can risk stratify patients for clinically significant prostate cancer. To ensure the generalizability of assay results we optimized and validated the clinical model for men with serum prostate specific antigen less than 10 ng/ml who were undergoing initial prostate biopsy., Materials and Methods: Urine samples were collected from 1,955 men from The Netherlands, France and Germany prior to an initial prostate biopsy and study subjects were divided into training and validation cohorts. Urinary HOXC6 and DLX1 mRNA levels were quantified and RNA results were then combined with other risk factors in a clinical model optimized to detect ISUP (International Society of Urological Pathology) Grade Group 2 or greater prostate cancer in men with prostate specific antigen less than 10 ng/ml. Results in the validation cohort were compared with the PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), version 2.0., Results: The optimal clinical model included urinary HOXC6 and DLX1 mRNA levels, patient age, digital rectal examination and prostate specific antigen density (serum prostate specific antigen/prostate volume). In the 715 validation cohort subjects with prostate specific antigen less than 10 ng/ml the AUC was 0.82 with 89% sensitivity, 53% specificity and 95% negative predictive value. The PCPTRC AUC was 0.70. The full validation cohort of 916 men including all prostate specific antigen levels yielded an AUC of 0.85 with 93% sensitivity, 47% specificity and 95% negative predictive value. The PCPTRC AUC was 0.76., Conclusions: The 2-gene based urine assay, which is optimized for biopsy naïve patients with serum prostate specific antigen less than 10 ng/ml, demonstrated high sensitivity and negative predictive value to detect clinically significant prostate cancer. These data support using the test to help guide initial prostate biopsy decisions.

Introduction: There is an unmet need for noninvasive methods to better identify patients at increased risk for clinically significant prostate cancer. SelectMDx® is a molecular urine test validated for the detection of Gleason score 7 and higher cancers (ISUP [International Society of Urological Pathology] Grade Group 2-5). In this multicenter trial we evaluated the test's impact on prostate biopsy decision making in clinical practice., Methods: The study involved 5 U.S. community urology practices which sequentially enrolled 418 patients who received a SelectMDx test between May 2016 and April 2017 while undergoing evaluation for initial prostate biopsy. All tests were ordered by the urologist for patient management. We determined biopsy and prostate cancer detection rates in patients with SelectMDx positive versus SelectMDx negative results., Results: Of the 418 subjects evaluated with SelectMDx 253 (61%) had negative results and 165 (39%) had positive results. Subsequent biopsy rates for SelectMDx positive and negative cases were 60% (99) and 12% (32), respectively (p <0.001). Time from SelectMDx result to biopsy was shorter for those with positive vs negative results (median 2 vs 5 months, p=0.001). Of patients who underwent biopsy within 3 months of testing 71 (43%) with positive results underwent biopsy and 27 had cancers identified, including 10 greater than Grade Group 2. Of 9 patients with SelectMDx negative results (3.6%) who underwent biopsy 4 were diagnosed with cancer, all Grade Group 2 or less., Conclusions: SelectMDx had a significant impact on initial prostate biopsy decision making. Biopsy rates in SelectMDx positive cases were fivefold higher than in SelectMDx negative cases. These results describe the clinical utility of SelectMDx in real-world community urology practice.

Background: Better prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain., Objective: To evaluate the utility of both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population., Design, Setting, and Participants: Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. CCP scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components., Intervention: Active treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting., Outcome Measurements and Statistical Analysis: The primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests., Results and Limitations: The final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p<0.001), and there was no interaction with ancestry (p=0.20) or treatment (p=0.09). The CCR score was highly prognostic (HR 3.86; p<0.001), and as with the CCP score, there was no interaction with ancestry (p=0.24) or treatment (p=0.32). Limitations include the retrospective study design and the use of self-reported ancestry information., Conclusions: A CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables., Patient Summary: In this study we evaluated the ability of a combined molecular and clinical score to predict the progression of localized prostate cancer. We found that the combined molecular and clinical score predicted progression to metastasis regardless of patient ancestry or treatment. This suggests that the combined molecular and clinical score may be a valuable tool for determining the risk of metastasis in men with newly diagnosed prostate cancer in order to make appropriate treatment decisions., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS., Methods: The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort., Results: In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively)., Conclusions: The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery., Objective: To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC., Design, Setting, and Participants: The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients., Outcome Measurements and Statistical Analysis: The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed., Results and Limitations: A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07-2.09) and DSM (HR 2.49, 95% CI 1.53-4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n=338) and high-risk (n=202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p<0.001)., Conclusions: The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management., Patient Summary: In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine the prognostic utility of the cell cycle progression (CCP) score in men with National Comprehensive Cancer Network (NCCN)-defined low-risk prostate cancer (PCa) undergoing radical prostatectomy (RP)., Patients and Methods: Men who underwent RP for Gleason score ≤6 PCa at three institutions (Martini Clinic [MC], Durham Veterans Affairs Medical Center [DVA] and Intermountain Healthcare [IH]) were identified. The CCP score was obtained from diagnostic (DVA, IH) or simulated biopsies (MC). The primary outcome was biochemical recurrence (BCR; prostate-specific antigen ≥0.2 ng/mL) after RP. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards models in the subset of men meeting NCCN low-risk criteria and in the overall cohort., Results: Among the 236 men identified, 80% (188/236) met the NCCN low-risk criteria. Five-year BCR-free survival for the low (<0), intermediate (0-1) and high (>1) CCP score groups was 89.2%, 80.4%, 64.7%, respectively, in the low-risk cohort (P = 0.03), and 85.9%, 79.1%, 63.1%, respectively, in the overall cohort (P = 0.041). In multivariable models adjusting for clinical and pathological variables with the Cancer of the Prostate Risk Assessment (CAPRA) score, the CCP score was an independent predictor of BCR in the low-risk (hazard ratio [HR] 1.77 per unit score, 95% confidence interval [CI] 1.21, 2.58; P = 0.003) and overall cohorts (HR 1.41 per unit score, 95% CI 1.02, 1.96; P = 0.039)., Conclusion: In a cohort of men with NCCN-defined low-risk PCa, the CCP score improved clinical risk stratification of men who were at increased risk of BCR, which suggests the CCP score could improve the assessment of candidacy for active surveillance and guide optimum treatment selection in these patients with otherwise similar clinical characteristics., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Background: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging., Objective: We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP., Methods: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group., Results: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031)., Conclusions: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy.

Genomic testing may be a vital component in the medical management of patients with complex clinical phenotypes and cancer.