The diagnostic yield of the Meares & Stamey test can be significantly improved by symptom-based patient selection and the experience of the test performer.

BACKGROUND: Even if Meares-Stamey 4-glass (M&S) test is regarded a decisive tool for diagnosing prostatitis its use is only rarely performed in everyday clinical practice. Here, we analyze if the diagnostic yield of the M&S test could be improved by a pre-test categorization of patients due to undergo a M&S test. METHODS: All clinical and microbiological data of patients who underwent M&S test in two urological centers from January 2004 to December 2021 were analyzed in this retrospective cohort study. One center has a dedicated staff member for the study of prostatitis (Cohort I), while the other center is a general urological unit (Cohort II). All patients were divided into 3 groups on the basis of the assembled data: patients with symptoms related to prostatitis only (Group I), patients with symptoms related to both prostatitis and BPH (Group II), patients with symptoms related to BPH only (Group III). The rates of positive microbiological results in each group were compared. RESULTS: In the whole period, 9347 patients were analyzed and categorized as follows: Group I, 1884; Group II, 5151; Group III, 2312. Three-thousand and eight-hundred twenty-three patients showed positive culture results (40.9%). The most common isolated species was Escherichia coli (49.7%), followed by Enteroccus spp. (31.8%). The rates of positive M&S tests in the different symptom groups were: Group I, 1532 (81.4%); Group II, 1494 (29.0%); Group III, 797 (34.4%). The overall rate of positive M&S tests in each urology center showed that the center with a staff member who is dedicated to prostatitis studies (Cohort I) had a significantly higher rate of positive M&S tests than the general urological department (Cohort II) (64.3% vs 31.4%; p < 0.001). CONCLUSIONS: Symptom-based patient selection and dedicated staff members will increase the diagnostic yield of the M&S test and reduce the number of unnecessary tests.

Phytotherapy Might Have a Role in Reducing Unnecessary Prostate Biopsies: Results from an Exploratory, Randomized Controlled Trial of Two Different Phytotherapeutic Agents.

BACKGROUND: We aimed to evaluate the impact of two different phytotherapeutic agents on decision making regarding prostate biopsy for patients with higher-than-normal prostate-specific antigen (PSA) levels. METHODS: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B) for 3 months. At the follow-up visit after 3 months, all patients underwent PSA tests and multiparametric magnetic resonance imaging (mpMRI). RESULTS: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction in total PSA compared to forty-nine in Group B (64.4%) (p < 0.001). Twenty-eight patients had PI-RADS III or higher in mpMRI: twelve in Group A and fourteen in Group B. Twenty-three patients (34.8%) in Group A and fifty-nine (77.6%) in Group B (p < 0.001) underwent prostate biopsy based on the mpMRI findings and PSA values. Three patients in Group A showed a significant reduction in total PSA values while having positive mpMRI findings (6%) compared with nine in Group B (19.5%) (p < 0.001). On the contrary, 7 patients in Group A did not show significant reduction in total PSA values and had negative mpMRI findings (43%) compared to 22 in Group B (81.4%) (p < 0.001). CONCLUSIONS: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica seems to be an interesting tool to avoid unnecessary prostate biopsies among men with higher-than-normal PSA levels.

Management of Recurrent Cystitis in Women: When Prompt Identification of Risk Factors Might Make a Difference.

BACKGROUND: Management of recurrent urinary tract infection (rUTI) is still challenging. A better understanding of the natural history of rUTI could help us reduce antibiotic use and improve antibiotic stewardship. OBJECTIVE: To describe the effect of risk identification, stratification, and counseling on the natural course of the disease in women with rUTI. DESIGN, SETTING, AND PARTICIPANTS: A total of 373 women affected by recurrent cystitis were enrolled in this longitudinal cohort study between December 2014 and December 2019. A systematic and standardized identification of risk factors was performed. INTERVENTION: As intervention, risk factors were treated or removed where possible. Patients with nonremovable risk factors were included in the control group. All patients were scheduled for follow-up visits every 6 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome measures were the rate of symptomatic recurrences and improvement in questionnaire results from baseline to the end of the follow-up period. Reduction of antibiotic usage was regarded as a secondary outcome measure. RESULTS AND LIMITATIONS: Finally, 353 women were analyzed: 196 in the study group and 157 in the control group. At the end of the follow-up period, a statistically significant reduction in the symptomatic recurrence rate was found between the two groups (0.9 ± 0.2 and 2.6 ± 0.5; p < 0.001), as well as in quality of life and anxiety according to mean questionnaire results: quality of life (0.88 ± 0.06 and 0.63 ± 0.09; p < 0.001) and Spielberger State-Trait Anxiety Inventory-Form Y (32.7 ± 9.3 and 47.5 ± 14.3; p < 0.001). The use of antibiotics was significantly lower in the study group: 4410 versus 9821 (p < 0.001). A limitation to consider is the lack of a randomized design for the active approach in the high-risk group. CONCLUSIONS: Identification, counseling, and removal of risk factors, where possible, are able to change the natural history of rUTI, by reducing the number of symptomatic episodes and antibiotic use and improving quality of life. PATIENT SUMMARY: In this report, we analyzed a large cohort of women affected by recurrent urinary tract infections and followed for a long time period. We found that risk factor identification and counseling may change the natural history of recurrent urinary tract infections, concluding that this approach is able to reduce the number of symptomatic episodes, reduce antibiotic usage, and improve patients' quality of life.

Xyloglucan, Hibiscus and Propolis in the Management of Uncomplicated Lower Urinary Tract Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: In the era of antibiotic resistance, an antibiotic-sparing approach presents an interesting alternative treatment of uncomplicated cystitis in women. Our aim is to perform a systematic review and meta-analysis to compare the effectiveness and safety profile of a medical device containing xyloglucan, hibiscus and propolis (XHP) in women with uncomplicated cystitis. METHODS: Relevant databases were searched using methods recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was clinical or microbiological success, defined as the complete (cure) and/or non-complete (improvement) resolution of symptoms at the end of treatment, or microbiological resolutions. RESULTS: After screening 21 articles, three studies were included, recruiting a total of 178 patients. All three studies used placebo as comparator. A statistically significant difference was found in terms of clinical or microbiological resolution between the medical device and the comparator (3 RCTs, 178 patients, OR: 0.13; 95% CI: 0.05-0.33; p < 0.0001). No clinically significant adverse effects have been reported. CONCLUSION: A medical device containing xyloglucan, hibiscus and propolis is superior to comparator regimens in terms of clinical effectiveness in adult women with microbiologically confirmed or clinical suspicion of uncomplicated cystitis and is associated with a high patient compliance.

Fosfomycin trometamol and N-acetyl-L-cysteine as combined oral therapy of difficult-to-treat chronic bacterial prostatitis: Results of a pilot study.

This paper presents the results of a pilot study of difficult-to-treat patients (exhibiting several previous treatment failures or detection of extended-spectrum beta-lactamase [ESBL] strains) with chronic bacterial prostatitis (CBP) who underwent treatment with fosfomycin trometamol (FT) and N-acetyl-L-cysteine (NAC). Twenty-eight patients with clinically- and microbiologically-confirmed CBP who attended a single urological institution between January 2018 and March 2019 were treated with oral administration of 3 g FT once a day for 2 days, followed by a dose of 3 g every 48 h for 2 weeks, in combination with oral administration of NAC 600 mg once a day for 2 weeks. Clinical and microbiological analyses were carried out at the time of admission (T0) and during follow-up at 1 month (T1) and 6 months (T2) after the end of treatment. Symptoms were assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Prostatic Symptom Score (IPSS), and quality of life was assessed by Quality of Well-Being (QoL) questionnaires. Isolated strains were Escherichia coli (23 patients), Enterococcus spp. (3 patients), and Klebsiella oxytoca (2 patients). ESBL strain was found in 19 (67.8%) patients. Microbiological eradication was documented in 21 (75%) patients at the second follow-up visit and clinical cure was achieved in 20 (71.4%) patients. Significant changes on questionnaires were recorded between baseline and follow-up visits. Fifteen of 19 patients (78.9%) with ESBL strains were cured. No significant side effects were reported. FT in combination with NAC is a promising alternative therapy in difficult-to-treat CBP patients.

Fosfomycin Trometamol versus Comparator Antibiotics for the Treatment of Acute Uncomplicated Urinary Tract Infections in Women: A Systematic Review and Meta-Analysis.

PURPOSE: We performed a systematic review and meta-analysis to compare the effectiveness and safety profile of fosfomycin vs comparator antibiotics in women with acute uncomplicated cystitis. MATERIALS AND METHODS: Relevant databases were searched using methods recommended by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We assessed the risk of bias and confounders. The study primary end point was clinical or microbiological success, defined as complete (cure) and/or incomplete resolution of symptoms at the end of treatment (improvement) and/or microbiological eradication. RESULTS: After screening 539 articles 15 were included which recruited a total of 2,295 adult female patients. Of the studies 14 were used for microbiological eradication analysis. We used 11 of the 15 articles in a total of 1,976 patients for clinical resolution and 11 in a total of 1,816 patients for safety outcome analysis. No difference was found for clinical resolution in all comparators combined in 11 randomized controlled trials in a total of 1,976 patients (OR 1.16, 95% CI 0.91-1.49, p=0.13). No difference was found for microbiological eradication in 14 randomized controlled trials in a total of 2,052 patients (OR 1.03, 95% CI 0.83-1.30, p=0.09) or for safety outcome in 11 randomized controlled trials in a total of 1,816 patients (OR 1.17, 95% CI 0.86-1.58, p=0.33). Most adverse effects reported for fosfomycin were transient and single dose therapy seems to have resulted in better patient compliance. CONCLUSIONS: Single dose oral fosfomycin trometamol is equal to comparator regimens in terms of clinical and microbiological effectiveness and safety in women with microbiologically confirmed and/or clinically suspected, acute uncomplicated cystitis. It is associated with high patient compliance.

Current Knowledge of the Potential Links between Inflammation and Prostate Cancer.

Inflammation is inherent in prostatic diseases and it is now accepted that it may facilitate cellular proliferation in both benign and malignant conditions. The strong relationship between prostatic inflammation and pathogenesis of benign prostatic hyperplasia (BPH) is supported by epidemiologic, histopathologic and molecular evidence. Contrariwise, the role of inflammation in prostate carcinogenesis is still controversial, although current data indicate that the inflammatory microenvironment can regulate prostate cancer (PCa) growth and progression. Knowledge of the complex molecular landscape associated with chronic inflammation in the context of PCa may lead to the introduction and optimization of novel targeted therapies. In this perspective, evaluation of the inflammatory component in prostate specimens could be included in routine pathology reports.

Xyloglucan, hibiscus and propolis to reduce symptoms and antibiotics use in recurrent UTIs: a prospective study.

Aim: To evaluate the efficacy of a medical device containing xyloglucan, hibiscus and propolis in the management of recurrent urinary tract infections (rUTIs). Patients & methods: Sixty-one women affected by rUTIs received this medical device, one capsule a day for 15 days (one cycle every month, for 6 months), in an observational, prospective study. Clinical and microbiological evaluations were performed at baseline and 1, 3 and 6 months from enrolment. Results: At first follow-up, 41 reported a clinical improvement and a return to their clinical status before UTI, while 47 and 51 did so at the second and third follow-up evaluations. A statistically significant clinical improvement was reported at each follow-up visit (quality of life [QoL] 94.2 vs 98.6; QoL 94.1 vs 98.7; QoL 94.2 vs 99.1; p < 0.001). A statistically significant reduction in antibiotic use was reported. Conclusion: This medical device is able to improve quality of life in women with rUTIs, reduce recurrences and antibiotic use.

Low-Risk Prostate Cancer and Tumor Upgrading in the Surgical Specimen: Analysis of Clinical Factors Predicting Tumor Upgrading in a Contemporary Series of Patients Who were Evaluated According to the Modified Gleason Score Grading System.

OBJECTIVE: To identify significant clinical factors associated with prostate cancer (PCa) upgrading the low-risk PCa patients graded according to the modified Gleason score system. MATERIALS AND METHODS: The logistic regression model was used to evaluate the records of 438 patients. RESULTS: There were 170 cases (38.8%) of low-risk PCa and tumors were upgraded in 111 patients (65.3%). Only prostate specific antigen (PSA) and the proportion of positive cores (P+) were independent predictors of tumor upgrading. Further exploration was investigated by categorizing and regressing PSA (≤ 5.0 vs. > 5.0 ng/ml) and P+ (≤ 0.20 vs. > 0.20). The odds ratio of PSA > 5 ng/ml was 1.32 and of P+ > 0.20 was 2.71. The population was stratified into very low-risk with PSA ≤ 5 ng/ml and P+ ≤ 0.20 (class A), low-risk with PSA > 5 ng/ml and P+ ≤ 0.20 (class B), intermediate risk with PSA ≤ 5 ng/ml and P+ > 0.20 (class C), and high risk with PSA > 5 ng/ml and P+ 0.20 (class D). Upgrading rates were extremely low in class A (9%), extremely high in D (50.5%), and moderate (20%) in B and C. CONCLUSION: Patients diagnosed with low-risk PCa at biopsy are a heterogeneous population because they include subsets with undetected high-grade disease. Significant clinical predictors of upgrading include the PSA value and P+. In low-risk PCa, we identified a high-risk upgrading subgroup that needed repeat biopsies in order to reclassify the tumor grade and to reassess the clinical risk category.

Preoperative Plasma Levels of Total Testosterone Associated with High Grade Pathology-Detected Prostate Cancer: Preliminary Results of a Prospective Study in a Contemporary Cohort of Patients.

OBJECTIVES: To investigate the associations, if any, between preoperative plasma levels of total testosterone (TT) and pathology Gleason score (pGS) in a contemporary cohort of prostate cancer (PCa) patients. MATERIALS AND METHODS: Between November 2014 and June 2015, plasma levels of TT were measured in 142 patients who underwent radical prostatectomy. Exclusion criteria were as follows: 5α-reductase inhibitors, LH-releasing hormone analogues, or testosterone replacement treatment. The entire cohort, assessed by continuous and categorical variables, was classified into two groups according to the pGS that included low-intermediate (pGS 6-7) and high grade (pGS > 7) cases. TT was evaluated as a continuous variable. RESULTS: The cohort included 128 cases. High grade PCa was detected in 28 (21.8%) patients. Median plasma levels of both TT and prostate specific antigen (PSA) were significantly higher in these cases. In the clinical multivariate model, independent and positive predictors of pGS > 7 were TT (p = 0.041; OR = 1.004), PSA (p = 0.006; OR = 1.191), and bGS > 6 (p = 0.004; OR = 5.0); that is, a single unit increase in TT plasma levels increases the odds of having high grade PCa by 4%. CONCLUSION: In a contemporary cohort of patients, preoperative plasma levels of TT directly and independently associated with high grade PCa. High baseline plasma levels of TT might have clinical applications for managing PCa. New and well designed prospective studies dealing with this subject are required.

The role of nutraceuticals and phytotherapy in the management of urinary tract infections: What we need to know?

Urinary Tract Infections (UTIs) are amongst the most common infectious diseases and carry a significant impact on patient quality of life and health care costs. Despite that, there is no well-established recommendation for a "standard" prophylactic antibiotic management to prevent UTI recurrences. The majority of patients undergoes long-term antibiotic treatment that severely impairs the normal microbiota and increases the risk of development of multidrugresistant microorganisms. In this scenario, the use of phytotherapy to both alleviate symptoms related to UTI and decrease the rate of symptomatic recurrences is an attractive alternative. Several recently published papers report conflicting findings and cannot give confident recommendations for the everyday clinical practice. A new approach to the management of patients with recurrent UTI might be to use nutraceuticals or phytotherapy after an accurate assessment of the patient`s risk factors. No single compound or mixture has been identified so far as the best preventive approach in patients with recurrent UTI. We reviewed our non-antibiotic approach to the management of recurrent UTI patients in order to clarify the evidence-base for the commonly used substances, understand their pharmacokinetics and pharmacodynamics in order to tailor the best way to improve patient's quality of life and reduce the rate of antibiotic resistance. Lack of a gold-standard recommendation and the risk of increasing antibiotic resistance is the reason why we need alternatives to antibiotics in the management of urinary tract infections (UTIs). A tailored approach according to bacterial characteristics and the patient risk factors profile is a promising option.

Daidzein plus isolase associated with zinc improves clinical symptoms and quality of life in patients with LUTS due to benign prostatic hyperplasia: Results from a phase I-II study.

OBJECTIVE: In the last years there is a growing interest in nutraceutical substances that seems able to improve clinical symptoms in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). In this paper, we evaluated both efficacy and safety of a combination of daidzein with isolase and zinc in patients with LUTS due to BPH. MATERIALS AND METHODS: In a phase I-II study clinical trial we enrolled patients with clinical and instrumental diagnosis of LUTS associated to BPH that received a six-month treatment with a combination of daidzein with isolase and zinc (1 tablet/day). Clinical, laboratory and instrumental analyses were carried out at the time of admission (T0) and 6 months after the ending of the treatment (T1). The Italian version of International Prostatic Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and Quality of Well-Being (QoL) questionnaires were used. The development of adverse drug reactions (ADRs) and drug interactions (DDIs) were recorded using the Naranjo scale and drug interaction probability scale. Student's t test and Anova test were used for statistical analysis, and the threshold of statistical significance was set at P < 0.05. RESULTS: We enrolled 71 patients, 62 (87.3%) completed the follow-up and we documented a significant differences between T0 and T1 in terms of IPSS [21.5 ± 1.2 vs 16.2 ± 1.5; (-4.8); p < 0.001], Cmax [9.7 ± 3.7 vs 15.3 ± 2.5; (+5.6); p < 0.001] and QoL [0.56 ± 0.15 vs 0.84 ± 0.19; (+0.28); p < 0.001]. In contrast, no significant difference were recorded in terms of IIEF-5 [p = 0.50] and PSA [p = 0.67]. Finally, we did not record any significant ADRs or DDIs during the study. CONCLUSIONS: In this study, we documented that a combination of daidzein with isolase and zinc, reduces the clinical symptoms of LUTS and improves the quality of life in patients with BPH, without the development of ADRs or DDIs.

Prostate Volume Index Associates with a Decreased Risk of Prostate Cancer: Results of a Large Cohort of Patients Elected to a First Biopsy Set.

Background/Aims/Objectives: In patients elected to the first prostate biopsy set, the risk of prostate cancer (PCA) may be predicted by clinical factors. The aim of this study was to investigate on prostate volume index (PVI), defined as the ratio of volume of the transitional zone to the volume of the peripheral zone, and PCA risk. METHODS: The study retrospectively evaluated 1,327 patients and included only the first biopsy set with 14 cores. PCA risk was assessed by using the multivariate logistic regression model. RESULTS: The analysis evaluated 596 patients. The detection rate of PCA was 49%. Age, prostate specific antigen, PVI and digital rectal exam were independent factors of PCA risk, which was decreased by PVI (OR 0.224; 95% CI 0.157-0.380). The goodness of fit statistics assessed model efficacy. CONCLUSIONS: In a large cohort undergoing the first biopsy set, PVI associated with a decreased risk of PCA. Confirmatory studies are required.

Clinical Factors of Disease Reclassification or Progression in a Contemporary Cohort of Prostate Cancer Patients Elected to Active Surveillance.

OBJECTIVES: To evaluate clinical predictors of disease reclassification or progression (DR/P) in prostate cancer patients elected to active surveillance (AS). MATERIAL AND METHODS: Patients were assessed on the basis of DR/P criteria. Predictors of DR/P were evaluated by multivariate logistic regression and Cox proportional hazards. RESULTS: The median DR/P free time was 16.5 months. DR/P was detected in 30 out of 84 cases (35.7%). In DR/P cases, the median prostate volume (PV) was significantly lower (34.7 vs. 42.7 ml) and the percentage of cases with 2 or 3 vs. 1 initial biopsy positive cores (BPC) was significantly higher (36.7 vs. 7.4%). The multivariate logistic regression model showed that PV (OR 0.9; p = 0.021) and initial n >1 BPC (OR 9.8; p = 0.001) were independent predictors of DR/P. By Cox multivariate proportional hazards, only n >1 BPC predicted early DR/P (hazard ratio 3.1; p = 0.003). CONCLUSIONS: In a contemporary cohort of patients elected to AS, independent factors stratifying the risk of DR/P were PV and initial BPC, which also predicted early DR/P. In patients elected to AS, the identification of risk factors of DR/P require early re-biopsy. Confirmatory studies are required.

Bilateral lymph node micrometastases and seminal vesicle invasion associated with same clinical predictors in localized prostate cancer.

AIM: To determine clinical factors associated with multiple bilateral lymph node micrometastases and seminal vesicle invasion (pT3b) in organ-confined prostate cancer (PCa). METHODS: The study excluded patients under androgen deprivation, with lymph node involvement (cN1 status), and having undergone unilateral pelvic lymph node dissection (PLND) during radical prostatectomy (RP). Lymph node micrometastases were classified as unilateral (pN1m) and bilateral (pN1b). Analysis considered multivariate multinomial logistic regression models. RESULTS: Between January 2013 and March 2015, 140 patients underwent PLND during RP. Lymph node micrometastases were detected in 28 cases (20%) including pN1m in 19 (13.6%) and pN1b in 9 (6.4%). Independent clinical predictors of pN1b included prostate-specific antigen (PSA, µg/L) >12.5 (odds ratio [OR] = 43.0), proportion of positive biopsy cores (PBC) >0.57 (OR = 6.7), and biopsy Gleason grade (bGG) >3 (OR = 7.5). Independent pT3b predictors included PSA>12.5 (OR = 3.8), PBC>0.57 (OR = 4.1), and bGG>3 (OR = 3.8). CONCLUSIONS: In cN0 patients with localized PCa undergoing PLND, a nonnegligible rate of multiple lymph node micrometastases was detected (32.2%). In the natural history of PCa, there is a close association between pT3b and pN1b disease. Prostate cancer patients who are at high risk of extraglandular extension need selective pelvic staging by multiparametric magnetic resonance imaging to assess seminal vesicle invasion. Operated patients with pT3b and pNx status need close PSA monitoring because of the high probability of occult multiple bilateral lymph node micrometastases.

Chronic Inflammation in Prostate Biopsy Cores is an Independent Factor that Lowers the Risk of Prostate Cancer Detection and is Inversely Associated with the Number of Positive Cores in Patients Elected to a First Biopsy.

OBJECTIVES: To investigate associations of chronic inflammatory infiltrate (CII) with prostate cancer (PCa) risk and the number of positive cores in patients elected to a first set of biopsies. MATERIALS AND METHODS: Excluding criteria were as follows: active surveillance, prostate specific antigen (PSA) ≥ 30 ng/l, re-biopsies, incidental PCa, less than 14 cores, metastases, or 5-alpha reductase inhibitors. The cohort study was classified as negative (control group) and positive cores between 1 and 2 or > 2. RESULTS: The cohort included 421 cases who did not meet the exclusion criteria. PCa was detected in 192 cases (45.6%) of which the number of positive cores was between 1 and 2 in 77 (40.1%) cases. The median PSA was 6.05 ng/ml (range 0.3-29 ng/ml). Linear regression models showed that CII was an independent predictor inversely associated with the risk of PCa. Multinomial logistic regression models showed that CII was an independent factor that was inversely associated with PCa risk in cases with positive cores between 1 and 2 (OR = 0.338; p = 0.004) or more than 2 (OR = 0.076; p < 0.0001) when compared to the control group. CONCLUSION: In a cohort of men undergoing the first biopsy set after prostate assessment, the presence of CII in the biopsy core was an independent factor inversely associated with PCa risk as well as with the number of positive biopsy cores (tumor extension). Clinically, the detection of CII in negative biopsy cores might reduce the risk of PCa in repeat biopsies as well as the probability of detecting multiple positive cores.

Low-Risk Prostate Cancer and Tumor Upgrading to Higher Patterns in the Surgical Specimen. Analysis of Clinical Factors Predicting Tumor Upgrading to Higher Gleason Patterns in a Contemporary Series of Patients Who Have Been Evaluated According to the Modified Gleason Score Grading System.

OBJECTIVE: To identify clinical factors associated with prostate cancer (PCA) upgrading to higher patterns of the surgical specimen in low-risk PCA. MATERIALS AND METHODS: We evaluated the records of 438 patients. The multinomial logistic regression model was used. RESULTS: Low-risk PCA included 170 cases (38.8%) and tumor upgrading was detected in 111 patients (65.3%) of whom 72 (42.4%) had pathological Gleason patterns (pGP) = 3 + 4 and 39 (22.9%) pGP >3 + 4. Prostate-specific antigen (PSA) and proportion of positive cores (P+) were independent predictors of tumor upgrading to higher patterns. The main difference between upgraded cancers related to PSA and to P+ >0.20. The population was stratified into risk classes by PSA ≤5 µg/l and P+ ≤0.20 (class A), PSA >5 µg/l and P+ ≤0.20 (class B), PSA ≤5 µg/l and P+ >0.20 (class C) and PSA >5 µg/l and P+ 0.20 (class D). Upgrading rates to pGP >3 + 4 were extremely low in class A (5.1%), extremely high in D (53.8%). CONCLUSIONS: Low-risk PCA is a heterogeneous population with significant rates of undetected high-grade disease. Significant clinical predictors of upgrading to higher patterns include PSA and P+, which identify a very high-risk class that needs repeat biopsies in order to reclassify tumor grade.

High Testosterone Preoperative Plasma Levels Independently Predict Biopsy Gleason Score Upgrading in Men with Prostate Cancer Undergoing Radical Prostatectomy.

PURPOSE: The study aims to investigate the potential associations between preoperative plasma levels of total testosterone (TT) and biopsy Gleason score (bGS) upgrading in prostate cancer (PCA) patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Exclusion criteria were treatment with 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement. Criteria of bGS upgrading were as follows: (i) bGS 6 to pathological Gleason score (pGS) >6, (ii) bGS 7 with pattern 3 + 4 to pGS 7 with pattern 4 + 3 or to pGS >7, (iii) bGS 7 with pattern 4 + 3 to pGS >7. Patients who showed bGS >7 were excluded from the cohort. RESULTS: The study included 209 patients. Tumor upgrading was assessed in 76 (36.4%) cases of the entire cohort, in 51 out of 130 cases (39.2%) of the bGS 6 group and 25 out of 79 patients (31.6%) in the bGS 7 cluster. Logistic regression models showed that independent clinical covariates predicting the risk of bGS upgrading included TT (OR 1.058; p = 0.027) and prostate-specific antigen (PSA) density (OR 23.3; p = 0.008) as well as TT (OR 1.057; p = 0.029) with PSA (OR 1.061; p = 0.023). The model suggests that 1 unit increase in TT plasma levels increases the odds of bGS upgrading by 5.8 or 5.7%. CONCLUSIONS: In summary, we have determined that high TT preoperative plasma levels independently predict bGS upgrading in men with PCA undergoing RP. Preoperative plasma levels of TT might be included as a potential marker for assessing the risk bGS upgrading.

Prostate cancer volume associates with preoperative plasma levels of testosterone that independently predicts high grade tumours which show low densities (quotient testosterone/tumour volume).

OBJECTIVE: To investigate potential associations of preoperative total testosterone (TT) with tumor volume (TV) and grade of prostate cancer (PCa). METHODS: Patients who were under medications impacting on the hypothalamic-pituitary-adrenal-testis-prostate axis were excluded. TT was measured preoperatively at least 1 month after biopsies and TV was calculated on the removed prostate specimen. Other continuous variables included total prostate specific antigen (PSA), percentage of positive cores (P+) and weight (W) of the removed prostate. Patients were categorized according to the pathologic Gleason score (pGS) in 3 groups (pGS 6, 7 and > 7). Invasion of the seminal vesicles was coded as seminal vesicle invasion (SVI). RESULTS: The median levels of TT were significantly and increasingly higher from pGS 6 (14.7 nmol/L) to pGS 7 (15.0 nmol/L) and pGS > 7 (18.8 nmol/L). The median values of TV were also detected significantly and increasingly higher from pGS 6 (5.6 mL) to pGS 7 (8.1 mL) and pGS > 7 (14.8 mL). The median preoperative levels of PSA were also increasing from pGS 6 (5.9 µg/L) to pGS 7 (6.2 µg/L) and pGS > 7 (7.7 µg/L). There was a significant and positive correlation of TV to PSA, TT and P+. Multiple linear regression analysis showed that TV was significantly and independently predicted by TT, PSA and P+. High grade PCa (pGS > 7) independently associated with TV, TT, P+ and SVI. The median density values of TT relative to TV (quotient TT/TV) significantly decreased from pGS 6 (2.6 nmol/L/mL) to pGS 7 (1.9 nmol/L/mL) and pGS > 7 (1.4 nmol/L/mL). The median density values of PSA relative to TV (quotient PSA/TV) also significantly decreased from pGS (1.1 µg/L/mL) to pGS 7 (0.7 µg/L/mL) and pGS > 7 (0.6 µg/L/mL). CONCLUSION: The investigation shows that TT relates to volume and grade of PCa; moreover, the density of TT relative to TV inversely associates with rate of increase of cancer that depends on the grade of the tumour.