The predictive power of free (vs. total) testosterone in aggressive prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16570-e16570
Author(s):  
Maxwell M Towe ◽  
Linda My Huynh ◽  
Farouk El Khatib ◽  
Mohamad M Osman ◽  
Faysal A Yafi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Free Testosterone ◽  
Protective Role ◽  
Current Data ◽  
Total Testosterone ◽  
Gleason Grade ◽  
Grade Group ◽  
Stage Disease ◽  
Prostate Cancers

e16570 Background: The role of testosterone in prostate growth and the development of prostate cancer is a controversial topic. Most current data suggest that lower testosterone leads to higher grade conversion, whereas higher testosterone may serve a protective role in preventing both development and recurrence. We seek to analyze whether free testosterone (FT) values can predict aggressiveness in prostate cancers. Methods: We retrospectively reviewed 830 patients who presented to a single surgeon for evaluation and management of prostate cancer. Total Testosterone (TT) and FT values were obtained on each patient at initial visit. All patients underwent radical prostatectomy and samples from surgery were sent for grading and staging. Patients were stratified by FT quartile (25th [≤ 4.42 ng/dL], 50th [4.43 – 5.60 ng/dL], 75th [5.61 – 6.95 ng/dL], and 100th [≥ 6.96 ng/dL]). Results: Of 830 patients, 168 (22.2%), 330 (39.8%), 188 (22.7%), 46 (5.5%), and 98 (11.8%) had GS 3+3, 3+4, 4+3, 4+4, and ≥4+5, respectively. Mean FT values for each Gleason grade group (GGG) were significantly different (p = 0.008). Mean FT was also lower in patients with higher stage disease (p = 0.01). In contrast, TT did not differ significantly among GGG (p = 0.489) or stage (p = 0.670). Patients who had a FT level in the lowest quartile (≤ 4.42 ng/dL) had a higher proportion of GGG 5 (15.6%) than patients in the highest quartile (≥ 6.96 ng/dL) (6.2%) (p = 0.002). After adjusting for age, prostate specific antigen (PSA), and body mass index (BMI) in multivariate analysis, lower FT was a significant predictor of high-risk score 9-10 (OR: 0.912, 95% CI: 0.836-0.994, p = 0.036). These trends showed strong correlation in pathologic stage (p = 0.057), but larger numbers are needed to gauge effect size. Conclusions: Based on our data, biochemically low FT may be a risk factor for high grade and high stage cancer. These results have implications for the current recommendations for testosterone therapy, which is contraindicated in men with prostate cancer. [Table: see text]

scholarly journals CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade

2020 ◽  
pp. 382-392 ◽  
Author(s):  
Michael T. Schweizer ◽  
Gavin Ha ◽  
Roman Gulati ◽  
Landon C. Brown ◽  
Rana R. McKay ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
High Rate ◽  
Gleason Grade ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Grade Group ◽  
Distinct Subgroup

PURPOSE Translational studies have shown that CDK12 mutations may delineate an immunoresponsive subgroup of prostate cancer, characterized by high neo-antigen burden. Given that these mutations may define a clinically distinct subgroup, we sought to describe outcomes to standard drugs and checkpoint inhibitors (CPI). PATIENTS AND METHODS Clinical data from consecutive patients with CDK12 mutations were retrospectively collected from 7 centers. Several clinical-grade sequencing assays were used to assess CDK12 status. Descriptive statistics included PSA50 response rate (≥ 50% decline in prostate-specific antigen from baseline) and clinical/radiographic progression-free survival (PFS). RESULTS Of 52 patients with CDK12-mutated prostate cancer, 27 (52%) had detected biallelic CDK12 alterations. At diagnosis, 44 (88%) had Gleason grade group 4-5, 52% had T3-T4, and 14 (27%) had M1 disease. Median follow-up was 8.2 years (95% CI, 5.6 to 11.1 years), and 49 (94%) developed metastatic disease. Median overall survival from metastasis was 3.9 years (95% CI, 3.2 to 8.1 years). Unconfirmed PSA50 response rates to abiraterone and enzalutamide in the first-line castration-resistant prostate cancer setting were 11 of 17 (65%) and 9 of 12 (75%), respectively. Median PFS on first-line abiraterone and enzalutamide was short, at 8.2 months (95% CI, 6.6 to 12.6 months) and 10.6 months (95% CI, 10.2 months to not reached), respectively. Nineteen patients received CPI therapy. PSA50 responses to CPI were noted in 11%, and PFS was short; however, the estimated 9-month PFS was 23%. PFS was higher in chemotherapy-naïve versus chemotherapy-pretreated patients (median PFS: not reached v 2.1 months, P = .004). CONCLUSION CDK12 mutations define an aggressive prostate cancer subgroup, with a high rate of metastases and short overall survival. CPI may be effective in a minority of these patients, and exploratory analysis supports using anti–programmed cell death protein 1 drugs early. Prospective studies testing CPI in this subset of patients with prostate cancer are warranted.

scholarly journals Basal total testosterone serum levels predict biopsy and pathological ISUP grade group in a large cohort of Caucasian prostate cancer patients who underwent radical prostatectomy

2020 ◽  
Vol 12 ◽  
pp. 175628722092948
Author(s):  
Alessandro Tafuri ◽  
Marco Sebben ◽  
Riccardo Rizzetto ◽  
Nelia Amigoni ◽  
Aliasger Shakir ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Stage ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Positive Association ◽  
Multivariate Model ◽  
Total Testosterone ◽  
Grade Group ◽  
Surgical Specimen ◽  
Grade Groups

Aims: The study aimed to evaluate associations of preoperative total testosterone (TT) with the risk of aggressive prostate cancer (PCA). Materials & methods: From 2014 to 2018, basal TT levels were measured in 726 consecutive PCA patients. Patients were classified according to the International Society of Urologic Pathology (ISUP) system. Aggressive PCA was defined by the detection of ISUP > 2 in the surgical specimen. The logistic regression model evaluated the association of TT and other clinical factors with aggressive PCA. Results: On univariate analysis, there was a significant association of basal TT with the risk of aggressive PCA as well as age, prostate-specific antigen (PSA), percentage of biopsy positive cores (BPC), tumor clinical stage (cT), and biopsy ISUP grade groups. On multivariate analysis, two models were considered. The first (model I) excluded biopsy ISUP grading groups and the second (model II) included biopsy ISUP grade groups. Multivariate model I, revealed TT as well as all other variables, was an independent predictor of the risk of aggressive disease [odds ratio (OR) = 1.585; 95% confidence interval (CI): 1.113–2.256; p = 0.011]. Elevated basal PSA greater than 20 µg/dl was associated with the risk of aggressive PCA. Multivariate model II revealed that basal TT levels maintain a positive association between aggressive PCA, whereas age, BPC, and clinical stage cT3 lost significance. In the final adjusted model, the level of risk of TT did not change from univariate analysis (OR = 1.525; 95% CI: 1.035–2.245; p = 0.011). Conclusion: Elevated preoperative TT levels are associated with the risk of aggressive PCA in the surgical specimen. TT may identify patients who are at risk of aggressive PCA in the low and intermediate European Association of Urology (EAU) risk classes.

scholarly journals Race and prostate imaging: implications for targeted biopsy and image-based prostate cancer interventions

2019 ◽  
Vol 1 (1) ◽  
pp. e000010
Author(s):  
Michael D Gross ◽  
Bashir Al Hussein Al Awamlh ◽  
Jonathan E Shoag ◽  
Elizabeth Mauer ◽  
Samprit Banerjee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Asian Americans ◽  
Asian American ◽  
Specific Antigen ◽  
Gleason Grade ◽  
Targeted Biopsy ◽  
Grade Group ◽  
Prostate Mri ◽  
Prostate Imaging ◽  
Asian American Men

PurposeFor men with an elevated prostate-specific antigen (PSA), there is a strong evidence for prostate MRI to assess the risk of clinically significant prostate cancer (CSPC) and guide targeted-biopsy interventions. Prostate MRI is assessed using the Prostate Imaging-Reporting and Data System (PI-RADS), which is scored from 1 to 5. Equivocal or suspicious findings (PI-RADS 3–5) are recommended for subsequent targeted biopsy, for which the risk of infection and sepsis is increasing. However, PI-RADS was developed primarily in men of European descent. We sought to elucidate PI-RADS and MRI-targeted biopsy outcomes in Asian men, a rapidly growing population in the USA, Europe, Australia and internationally.Materials and methodsA prospective cohort of 544 men with elevated PSA without a diagnosis of prostate cancer who underwent MRI-targeted biopsy at our institution from January 2012 to December 2018 was analyzed. We categorized the cohort by self-designated race then used a validated algorithm which uses surname lists to identify a total of 78 (14%) Asian-Americans. The primary outcome was the likelihood of diagnosing CSPC (Gleason grade group >1) in Asian-Americans versus non-Asian-Americans. Multivariable logistic regression was used to determine the association of demographic and other characteristics with CSPC.ResultsOverall, MRI-targeted biopsy identified CSPC in 17% of Asian-American men versus 39% of non-Asian-American men (p<0.001). Notably for PI-RADS 3, only 6% of Asian-Americans versus 15% of others were diagnosed with CSPC. In adjusted analyses, Asian-American men were less likely to be diagnosed on MRI-targeted biopsy with CSPC (OR 0.30, 95% CI 0.14 to 0.65, p=0.002) and indolent prostate cancer (OR 0.37, 95% CI 0.15 to 0.91, p=0.030) than other races. Regardless of race those who were biopsy naïve were more likely (OR 2.25, 95% CI 1.45 to 3.49, p<0.001) to be diagnosed with CSPC.ConclusionWe found that PI-RADS underperforms in Asian-American men. For instance, only 2 of 35 (6%) Asian-American men with PI-RADS 3 were diagnosed with CSPC on MRI targeted biopsy. This has significant implications for overuse of diagnostic and image-guided interventional approaches in Asian-Americans, given the increasing risk of infectious complications from biopsy. Additional validation studies are needed to confirm our findings.

scholarly journals Clinical relevance of semaphorin-3F in patients with prostate cancer

2019 ◽  
Vol 42 (3) ◽  
pp. E64-E69
Author(s):  
Guanlin Wu
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Enrichment Analysis ◽  
Tnm Staging ◽  
Gene Set Enrichment Analysis ◽  
Gleason Grade ◽  
Grade Group ◽  
Normal Prostate ◽  
Semaphorin 3F ◽  
Microarray Datasets

Purpose: To identify prognosis predictors for patients with prostate cancer (PCa). Methods: Four independent PCa microarray datasets (GSE32448, GSE16560, GSE79957 and GSE17951) were reanalyzed to characterize the expression of semaphorin-3F (SEMA3F) gene between PCa patients and normal prostate tissues and the correlation between SEMA3F expression and the age, tumor/nodes/metastasis (TNM) staging, Gleason Grade Group, prostate-specific antigen level and overall survival of PCa patients. Gene set enrichment analysis was applied to investigate the potential relevant mechanisms regarding the expression of SEMA3F and the proliferation of PCa cells. Results: The level of SEMA3F was significantly higher in normal prostate tissues compared with that in PCa cells (P

scholarly journals International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2627
Author(s):  
Andreas G. Wibmer ◽  
Michael W. Kattan ◽  
Francesco Alessandrino ◽  
Alexander D. J. Baur ◽  
Lars Boesen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Gleason Grade ◽  
Mri Findings ◽  
Grade Group ◽  
Mri Features ◽  
The Usa ◽  
Specific Prediction ◽  
Extraprostatic Extension

Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data. Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models (p < 0.001 for all). Conclusions: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.

Optimization of Risk Stratification in Localized Prostate Cancer

2018 ◽  
Vol 36 (6) ◽  
pp. 528-532 ◽  
Author(s):  
Alicia Katherine Morgans
Keyword(s):  
Prostate Cancer ◽  
Relevant Literature ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Localized Prostate Cancer ◽  
Gleason Grade ◽  
Management Options ◽  
Grade Group ◽  
The Right

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 67-year-old retired engineering professor was found to have a prostate-specific antigen (PSA) level of 11 ng/mL on a screening test at his annual physical examination. A digital rectal examination revealed a nodule on the right side. He underwent a transrectal ultrasound-guided prostate biopsy that was notable for prostate adenocarcinoma, Gleason 3 + 4 = 7 (Gleason grade group 2; 30% Gleason 4 component) involving two cores (60% and 20% core involvement). A bone scan and pelvic computed tomography scan were negative for evidence of metastatic disease. (Should he undergo prostate magnetic resonance imaging? That seems rather common these days.) He was diagnosed with cT2b intermediate-risk localized prostate cancer (PCa) by National Comprehensive Cancer Network (NCCN) risk group and was seen in the multidisciplinary clinic to discuss management options (Table 1).

scholarly journals Active surveillance in intermediate-risk prostate cancer with PSA 10–20 ng/mL: pathological outcome analysis of a population-level database

2021 ◽  
Author(s):  
Peter E. Lonergan ◽  
Chang Wook Jeong ◽  
Samuel L. Washington ◽  
Annika Herlemann ◽  
Scarlett L. Gomez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Outcome Analysis ◽  
Risk Category ◽  
Gleason Grade ◽  
Intermediate Risk ◽  
Grade Group ◽  
Risk Prostate Cancer

Abstract Background Active surveillance (AS) is generally recognized as the preferred option for men with low-risk prostate cancer. Current guidelines use prostate-specific antigen (PSA) of 10–20 ng/mL or low-volume biopsy Gleason grade group (GG) 2 as features that, in part, define the favorable intermediate-risk disease and suggest that AS may be considered for some men in this risk category. Methods We identified 26,548 men initially managed with AS aged <80 years, with clinically localized prostate cancer (cT1-2cN0M0), PSA ≤ 20 ng/mL, biopsy GG ≤ 2 with percent positive cores ≤33% and who converted to treatment with radical prostatectomy from the surveillance, epidemiology, and end results prostate with the watchful waiting database. Multivariable logistic regression was performed to determine predictors of adverse pathology at RP according to PSA level (<10 vs 10–20 ng/mL) and GG (1 vs 2). Results Of 1731 men with GG 1 disease and PSA 10–20 ng/mL, 382 (22.1%) harbored adverse pathology compared to 2340 (28%) of 8,367 men with GG 2 and a PSA < 10 ng/mL who had adverse pathology at RP. On multivariable analysis, the odds of harboring adverse pathology with a PSA 10–20 ng/mL (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.71–2.05, p < 0.001) was less than that of GG 2 (OR 2.56, 95%CI 2.40–2.73, p < 0.001) after adjustment. Conclusions Our results support extending AS criteria more permissively to carefully selected men with PSA 10–20 ng/mL and GG 1 disease.

scholarly journals The preoperative serum ratio of total prostate specific antigen (PSA) to free testosterone (FT), PSA/FT index ratio, and prostate cancer. Results in 220 patients undergoing radical prostatectomy

2016 ◽  
Vol 88 (1) ◽  
pp. 17 ◽  
Author(s):  
Antonio B. Porcaro ◽  
Beatrice Caruso ◽  
Alessandro Terrin ◽  
Nicolò De Luyk ◽  
Giovanni Cacciamani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Prostate Specific Antigen ◽  
Statistical Significance ◽  
Specific Antigen ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Preoperative Serum ◽  
Total Prostate Specific Antigen ◽  
Index Ratio

Objectives: To evaluate associations of preoperative total prostate specific antigen (PSA) to free testosterone (FT), the PSA/FT index ratio, with features of pathology prostate cancer (PCA) and to investigate its prognostic potential in clustering the PCA population. Patients and methods: After excluding criteria, the records of 220 patients who underwent radical prostatectomy (RP) were retrospectively reviewed. Serum samples of PSA, total testosterone (TT) and FT were collected at 8.00 A.M., one month after biopsies and before RP. The PSA/FT ratio was computed in the population of patients who were clustered in groups according to ranking intervals of the PSA/FT ratio which identified at least 4 clusters which were coded as A, B, C, and D. The independent associations of the PSA/FT index ratio were assessed by statistical methods and a two-sided P &lt; 0.05 was considered to indicate statistical significance. Results: TT correlated to FT which was a significant predictor of PSA in the population of patients who were subsequently clustered, according to increasing interval values of the PSA/FT index ratio, in groups that showed a stronger linear association of FT with PSA. The PSA/FT index ratio significantly associated with pathology features of prostate cancer such as pathology Gleason score (pGS), invasion of the seminal vesicles (pT3b), proportion of positive cores (P+) and proportion of cancer involving the volume of the prostate. In the population of patients, TT, PSA/FT index ratio and P+ independently associated with pGS ≥ 7 and pT3b; moreover, the odds ratio (OR) of the PSA/FT index ratio resulted 9.11 which was stronger than TT (OR = 1.11) and P+ (OR = 8.84). In the PCA population, TT, PSA/FT index ratio and P+ also independently associated with pT3b PCA; interestingly, the OR of PSA/FT index resulted 54.91 which was stronger than TT (OR = 1.31) and P+ (26.43). Conclusions: Preoperative PSA/FT index ratio is an independent strong factor which directly associates with aggressive features of pathology PCA; moreover, it might express prognostic potential for clustering the patient population in risk classes. Confirmatory studies are required.

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