The Influence of Endogenous Testosterone on Incidental Prostate Cancer after Transurethral Prostate Resection.

OBJECTIVE: The aim of the study was to test the hypothesis that endogenous total testosterone (TT) may relate to incidental prostate cancer (iPCA) in patients with lower urinary tract symptoms (LUTS) associated with prostate enlargement undergoing transurethral resection of the prostate (TURP). METHODS: The hypothesis was tested in contemporary cohort of patients who underwent TURP because of LUTS due to prostate enlargement after excluding the suspect of PCA. In period running from January 2017 to November 2019, 389 subjects were evaluated. Endogenous testosterone was measured preoperatively between 8:00 and 10:00 o'clock in the morning. Relationships between TT and iPCA were evaluated by statistical methods. RESULTS: Overall, iPCA was detected in 18 cases (4.6%) with clinical stage cT1a or International Society of Urologic Pathology (ISUP) < 2 in 11 patients (61.1%). Endogenous testosterone was inversely associated with age and BMI in the study population but not in the subgroup with iPCA in wholly endogenous TT strongly correlated to both number of chips involved by cancer (Pearson's correlation coefficient, r = 0.553; p = 0.017) and ISUP > 2 (r = 0.504; p = 0.033). The positive association of endogenous TT with both tumor load and tumor grade was confirmed by the linear regression model with high-regression coefficients for the former (regression coefficient, b = 0.307; 95% confidence interval, 95% CI: 0.062-0.551; and p = 0.017) as for the latter (b = 5.898; 95% CI: 0.546-11.249; and p = 0.033). CONCLUSIONS: Preoperative endogenous TT is associated with features of iPCA. The influence of iPCA on endogenous testosterone needs to be addressed by a large multicenter prospective trial.

The impact of extended pelvic lymph node dissection on the risk of hospital readmission within 180 days after robot assisted radical prostatectomy.

OBJECTIVE: To evaluate the factors associated with the risk of hospital readmission after robot assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND) for prostate cancer (PCA) over a long term. MATERIALS AND METHODS: The risk of readmission was evaluated by clinical, pathological, and perioperative factors. Skilled and experienced surgeons performed the procedures. Patients were followed for complications and hospital readmission for a period of six months. The logistic regression model and Cox's proportional hazards assessed the association of factors with the risk of readmission. RESULTS: From January 2013 to December 2018, 890 patients underwent RARP; ePLND was performed in 495 of these patients. Hospital readmission was detected in 25 cases (2.8%); moreover, it was more frequent when RARP was performed with ePLND (4.4% of cases) than without (0.8% of patients). On the final multivariate model, ePLND was the only independent factor that was positively associated with the risk of hospital readmission (hazard ratio, HR = 5935; 95%CI 1777-19,831; p = 0.004). CONCLUSIONS: Over the long term after RARP for PCA, the risk of hospital readmission is associated with ePLND. In patients who underwent RARP and ePLND, 4.4% of them had a readmission, compared to RARP alone, in which only 0.8% of cases had a readmission. When ePLND is planned for staging pelvic lymph nodes, patients should be informed of the increased risk of hospital readmission.

Predictive Factors of the Risk of Long-Term Hospital Readmission after Primary Prostate Surgery at a Single Tertiary Referral Center: Preliminary Report.

OBJECTIVE: To evaluate the predictors of the risk of long-term hospital readmission after radical prostatectomy (RP) in a single tertiary referral center where both open RP (ORP) and robot assisted RP (RARP) are performed. MATERIALS AND METHODS: The risk of readmission was evaluated by clinical, pathological, and perioperative factors. Skilled and experienced surgeons performed the 2 surgical approaches. Patients were followed for complications and hospital readmission for a period of 6 months. The association of factors with the risk of readmission was assessed by Cox's multivariate proportional hazards. RESULTS: From December 2013 to 2017, 885 patients underwent RP. RARP was performed in 733 cases and ORP in 152 subjects. Extended pelvic lymph node dissection (ePLND) was performed in 479 patients. Hospital readmission was detected in 46 cases (5.2%). Using a multivariate model, independent factors associated with the risk of hospital readmission were seminal vesicle invasion (hazard ratio [HR] 2.065; 95% CI 1.116-3.283; p = 0.021), ORP (HR 3.506; 95% CI 1.919-6.405; p < 0.0001), and ePLND (HR 5.172; 95% CI 1.778-15.053; p < 0.0001). CONCLUSIONS: In a large single tertiary referral center, independent predictors of the risk of long-term hospital readmission after RP included ORP, ePLND, and seminal vesicle invasion. When surgery is chosen as a primary treatment of PCA, patients should be informed of the risk of long-term hospital readmission and its related risk factors.

Positive Association between Basal Total Testosterone Circulating Levels and Tumor Grade Groups at the Time of Diagnosis of Prostate Cancer.

INTRODUCTION: To test the hypothesis that basal total testosterone (TT) levels are associated with International Society of Urologic Pathology (ISUP) tumor grade groups at the time of diagnosis of prostate cancer (PCA). METHODS: From November 2014 to March 2018, preoperative TT and PSA were measured in 601 consecutive patients who were not under androgen deprivation and undergoing surgery for PCA. Patients were classified into low (ISUP 1; reference group), intermediate (ISUP 2/3), and high (ISUP 4/5) tumor grade groups. The association of TT and other clinical factors with tumor groups was evaluated by multinomial multivariate regression analysis. RESULTS: 218 patients (36.3%) were biopsy low grade (ISUP 1), 297 (49.4%) intermediate grade (ISUP 2/3), and 86 (14.3) high grade (ISUP 4/5). Median basal circulating TT levels progressively increased as tumor grade groups increased. On multivariate models, TT, among other clinical factors, was positively associated with the risk of intermediate (OR 1.001; p = 0.023) and high tumor grades (OR 1.002, p = 0.022) compared to low-grade cancers. CONCLUSIONS: Increased endogenous circulating basal TT levels were positively associated with ISUP tumor grade groups at the time of diagnosis indicating a close association with tumor biology. Basal TT levels may reflect the heterogeneity of the cancer population.

Association between ABO blood group and unfavorable prostate cancer features after radical prostatectomy: Retrospective study of 1149 patients.

Objectives: To test hypothesized associations between the ABO blood group (ABO-bg) system and the pathological features of prostate cancer (PCa). Material and methods: Between January 2013 and September 2019, 1173 patients underwent radical prostatectomy. Associations between ABO-bg levels and pathological features were evaluated using statistical methods. Results: Overall, 1149 consecutive patients were evaluated using the ABO-bg system, which was represented by O-bg (42.8%) and A-bg (41.3%), followed by B-bg (11.1%) and AB-bg (4.8%). Only positive surgical margins (PSMs) was correlated with ABO-bg (Pearson correlation coefficient, r = 0.071; p = 0.017), and the risk was increased in group-O (odds ratio [OR], 1.497; 95% confidence interval, 1.149-1.950; p = 0.003) versus non-O-bg. In clinical and pathological models, O-bg was at increased risk of PSM after the adjustment for prostate-specific antigen, percentage of biopsy-positive cores, and high surgical volume (adjusted OR, 1.546; 95% confidence interval, 1.180-2.026; p = 0.002); however, the adjusted OR did not change after the adjustment for tumor load and stage as well as high surgical volume. Conclusions: In clinical PCa, the risk of PSM was higher in O-bg versus non-O-bg patients after the adjustment for standard predictors. Confirmatory studies are needed to confirm the association between ABO-bg and unfavorable PCa features.

Severe intraoperative bleeding predicts the risk of perioperative blood transfusion after robot-assisted radical prostatectomy.

To evaluate potential factors associated with the risk of perioperative blood transfusion (PBT) with implications on length of hospital stay (LOHS) and major post-operative complications in patients who underwent robot-assisted radical prostatectomy (RARP) as a primary treatment for prostate cancer (PCa). In a period ranging from January 2013 to August 2019, 980 consecutive patients who underwent RARP were retrospectively evaluated. Clinical factors such as intraoperative blood loss were evaluated. The association of factors with the risk of PBT was investigated by statistical methods. Overall, PBT was necessary in 39 patients (4%) in whom four were intraoperatively. Positive surgical margins, operating time and intraoperative blood loss were associated with perioperative blood transfusion on univariate analysis. On multivariate analysis, the risk of PBT was predicted by intraoperative blood loss (odds ratio, OR 1.002; 95% CI 1.001-1.002; p < 0.0001), which was associated with prolonged operating time and elevated body mass index (BMI). PBT was associated with delayed LOHS and Clavien-Dindo complications > 2. In patients undergoing RARP as a primary treatment for PCa, the risk of PBT represented a rare event that was predicted by severe intraoperative bleeding, which was associated with increased BMI as well as with prolonged operating time. In patients who received a PBT, prolonged LOHS as well as an elevated risk of major Clavien-Dindo complications were seen.

ABO blood group system and risk of positive surgical margins in patients treated with robot-assisted radical prostatectomy: results in 1114 consecutive patients.

To test the hypothesis of associations between the ABO blood group system (ABO-bg) and prostate cancer (PCa) features in the surgical specimen of patients treated with robot-assisted radical prostatectomy (RARP). Between January 2013 and October 2020, 1114 patients were treated with RARP. Associations of ABO-bg with specimen pathological features were evaluated by statistical methods. Overall, 305 patients were low risk (27.4%), 590 intermediate risk (50%) and 219 high risk (19.6%). Pelvic lymph node dissection was performed in 678 subjects (60.9%) of whom 79 (11.7%) had cancer invasion. In the surgical specimen, tumor extended beyond the capsule in 9.8% and invaded seminal vesicles in 11.8% of cases. Positive surgical margins (PSM) were detected in 271 cases (24.3%). The most frequently detected blood groups were A and O, which were equally distributed for both including 467 patients (41.9%), followed by groups B (127 cases; 11.4%) and AB (53 subjects; 4.8%). Among specimen factors, the ABO-bgs associated only with the risk of PSM, which was higher for blood group O (30.4%) compared with group A (19.5%) after adjusting for other standard clinical predictors (odds ratio, OR = 1.842; 95% CI 1.352-2.509; p < 0.0001). Along the ABO-bgs, the risk of PSM was increased by group O independently by other standard preoperative factors. The ABO-bgs may represent a further physical factor for clinical assessment of PCa patients, but confirmatory studies are required.

The Role of Emotional Condition in Patients With Lower Urinary Tract Symptoms Performing Uroflowmetry.

OBJECTIVE: To evaluate the prevalence of the general and uroflowmetry (UF)-related anxiety in patients performing UF, and to assess whether anxiety may affect patient's micturition at UF. MATERIALS AND METHODS: This prospective study recruited candidates to UF. Recorded data were: demographics, lower urinary tract symptoms (LUTS) and anxiety questionnaires (IPSS, ICIQ-FLUTS, GAD-7, APAIS-M), UF parameters, linker-type scale for UF satisfaction/reproducibility and discomfort. RESULTS: We enrolled 167 patients (non-naïve 59.3%). One hundred twenty-five were men. General anxiety was found in 55.3% of patients (63.2% naïve), and UF-related anxiety in 41.3% (46.5% non-naïve). No significantly different rate of anxiety was found between naïve and non-naïve patients. A significant difference was found between IPSS total score in patients without anxiety (10.9 ± 6.4) and subjects with anxiety (16.9 ± 7.3; P < 0001). According to the ICIQ-FLUTS questionnaire, only the subscore F was significantly greater in women with a high level of general and UF-related anxiety (7.8 ± 6.1 vs 12 ± 4.9; P < .001). A low UF satisfaction/reproducibility was reported by 27.5% of patients, in 21.7% of subjects with general anxiety, and 36.6% of patients with UF-related anxiety. High discomfort was recorded in 58.1% of patients. Anxiety affected women twice more than men, and patients with high anxiety had worse urinary symptoms. Non-naïve anxious patients had lower reproducibility of micturition and higher discomfort than naïve anxious candidates to UF. CONCLUSION: Several patients showed high general and UF-related anxiety at UF, had worse subjective feelings about the reproducibility of their habitual micturition patterns. In anxious patients, knowledge of UF did not avoid a lower reproducibility of micturition, nor a more considerable discomfort.

Incidental prostate cancer after transurethral resection of the prostate: analysis of incidence and risk factors in 458 patients.

BACKGROUND: The aim of this study is to evaluate the incidence and risk factors of incidental prostate cancer (IPCA) in a contemporary cohort of lower urinary tract symptoms (LUTS) patients who underwent trans-urethral resection of the prostate (TURP). METHODS: A series of 458 consecutive patients who underwent TURP were evaluated between January 2016 to June 2018. Evaluated factors included age (years), Body Mass Index (BMI; kg/square meters), treatment with inhibitors of 5-alpha reductase, previous prostate biopsies, basal prostate specific antigen (PSA) levels (ng/mL), serum leukocyte count (×109/L), weight of resected prostate tissue (grams), grade and stage of IPCA. The multivariate logistic regression model evaluated associations of significant clinical factors with the risk of IPCA. RESULTS: Overall, IPCA was detected in 30 of 454 patients (6.6%). A mean of 21.8 g of tissue was resected. The mean number of positive chips was 5.6 (mean percentage 3.9%) with tumor grade group 1 in 22 cases (73.4%) and tumor stage cT1a in 23 patients (76.7%). On multivariate analysis, independent factors that were positively associated with the risk of IPCA were BMI (odds ratio, OR=1.121; P=0.017) and leukocyte count (OR=1.144; P=0.027). CONCLUSIONS: In a contemporary cohort of patients undergoing TURP for the treatment of LUTS, the risk of IPCA was not negligible with a rate of being 6.6%. BMI and serum leukocyte count were found to be independent factors that were positively associated with the risk of IPCA.

Endogenous testosterone as a predictor of prostate growing disorders in the aging male.

OBJECTIVE: To investigate the associations of endogenous testosterone with prostate growing disorders (PGD) including benign prostatic hyperplasia (BPH) and prostate cancer (PCA). METHODS: The study population was composed by 1176 cases including 371 BPH subjects (31.5%) without cancer who underwent prostate transurethral resection from January 2017 to November 2019 and 805 patients (68.5%) with PCA who underwent surgery from November 2014 to December 2019. The association of endogenous testosterone, which was measured before surgery, with the risk of PGD was evaluated by statistical methods. RESULTS: In the study population, endogenous testosterone levels were significantly lower in PCA cases compared to BPH patients who were older with larger prostates but lower prostate-specific antigen (PSA) levels. On multivariate analysis, the risk of PCA decreased by endogenous testosterone (odds ratio, OR = 0.957; 95% CI 0.930-0.984; p = 0.002) as by age (OR = 0.955; 95% CI  0.933-0.984; p < 0,0001) and prostate volume (OR = 0.930; 95% CI 0.919-0.940; p < 0.0001) but increased by PSA (OR = 1.652; 95% CI 1.542-1.769; p < 0.0001). On multivariate linear regression analysis, endogenous testosterone inversely associated with body mass index (BMI) (regression coefficient, b = - 0.279; p = 0.002) and PCA (b = - 2.935; p < 0.0001). CONCLUSIONS: In the aging male, endogenous testosterone independently predicted malignant prostate disorders, which associated with decreased hormone levels along BMI categories. Endogenous testosterone is a further marker for evaluating prostate growing disorders in clinical practice; however, controlled studies are required.

Visualization of peri-prostatic neurovascular fibers before and after radical prostatectomy by means of diffusion tensor imaging (DTI) with clinical correlations: preliminary report.

To evaluate if diffusion tensor imaging (DTI) is able to detect morphological changes of peri-prostatic neurovascular fibers (PNF) before and after robot-assisted radical prostatectomy (RARP) and if these changes are related to urinary incontinence (UI) and erectile dysfunction (ED). From October 2014 and August 2017, 26 patients with biopsy-proven prostate cancer underwent prostatic multiparametric magnetic resonance imaging (mp-MRI) including DTI sequencing before, and 6 months after, RARP. Images were analyzed by placing six regions of interest (ROI), respectively, at base, mid gland, and apex, one for each side, to obtain tractographic reconstruction of the PNF. Patients were asked to complete International Consultation Incontinence Questionnaire-Short Form (ICIQ-SF) and International Index of Erectile Function (IIEF-5) questionnaires before RARP and 6 months post-operatively. Fractional anisotropy (FA), number (N), and length (L) of PNF before and after RARP were compared by means of Student's t test; Spearman's test was used to evaluate correlation between DTI parameters and questionnaires' scores. We observed a significant difference in N values before and after RARP (p < 0.001) and a negative correlation between IIEF-5 score and post-operative FA values at both the right (rho = - 0.42; p = 0.0456) and left (rho = - 0.66; p = 0.0006) base of the prostate. DTI with tractography of PNF is able to detect quantitative changes in N, L, and FA values in PNF after RARP. In particular, we observed an inverse correlation between FA of PNF and ED at 6 months after RARP. Further investigations are needed to confirm this trend.

Open approach, extended pelvic lymph node dissection, and seminal vesicle invasion are independent predictors of hospital readmission after prostate cancer surgery: a large retrospective study.

BACKGROUND: The aim of this study is to evaluate factors (clinical, pathological and perioperative) associated with the risk of hospital readmission after radical prostatectomy (RP) over the long term in a single tertiary referral center where both open RP (ORP) and robot assisted RP (RARP) are performed. METHODS: From January 2013 to December 2018 patients older than 18 years, who provided signed consent and underwent open or robot assisted radical prostatectomy were enrolled and retrospectively evaluated. Patients who underwent any previous prostate cancer (PCA) treatments were excluded. Specifically, skilled and experienced surgeons performed the two surgical approaches. Patients were followed for complications and hospital readmission (RAD) for a period of six months. The association of factors with the risk of readmission was assessed by Cox's multivariate proportional hazards. RESULTS: A total of 1062 patients underwent RP. RARP was performed in 891 cases and ORP in 171 subjects. Extended pelvic lymph node dissection (ePLND) was performed in 651 patients. Hospital readmission occurred in 53 cases (5%). Based on the final multivariate model, independent factors associated with the risk of hospital readmission were seminal vesicle invasion (HR=2.093; 95% CI: 1.177-3.722), ORP (HR=4.393; 95% CI: 2.516-7.672) and ePLND (HR=4.418; 95% CI: 1.544-12.639). CONCLUSIONS: ORP, ePLND and seminal vesicle invasion are independent predictors of the risk of hospital readmission over the long term at a large single tertiary referral center. When surgery is chosen as a primary treatment of PCA, patients should be informed of the risk of hospital readmission and related risk factors. Assessing seminal vesicle invasion by preoperative clinical staging identifies locally advanced disease, which is associated with an increased risk of hospital readmission.

Linear extent of positive surgical margin impacts biochemical recurrence after robot-assisted radical prostatectomy in a high-volume center.

The objective of this study is to evaluate if surgeon volume and stratifying positive surgical margins (PSM) into focal and non-focal may differentially impact the risk of biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). Between January 2013 and December 2017, 732 consecutive patients were evaluated. The population included negative cases (control group) and PSM subjects (study group). PSMs were stratified as focal (≤ 1 mm) or non-focal (> 1 mm). A logistic regression model assessed the independent association of factors with the risk of PSM. The risk of BCR of PSM and other factors was assessed by Cox's multivariate proportional hazards. Overall, 192 (26.3%) patients had PSM focal in 133 patients; non-focal in 59 cases. Focal PSM was associated with the percentage of biopsy positive cores (BPC; OR 1.011; p = 0.015), extra-capsular extension (pT3a stage; OR 2.064; p = 0.016), seminal vesicle invasion (pT3b; OR 2.150; p = 0.010), body mass index (odds ratio, OR 0.914; p = 0.006), and high surgeon volume (OR 0.574; p = 0.006). BPC (OR 1.013; p = 0.044), pT3a (OR 4.832; p < 0.0001) and pT3b stage (OR 5.153; p = 0.001) were independent predictors of the risk of non-focal PSM. Surgeon volume was not a predictor of non-focal PSM (p = 0.224). Independent factors associated with the risk of BCR were baseline PSA (hazard ratio, HR 1.064; p = 0.004), BPC (HR 1.015; p = 0.027), ISUP biopsy grade group (BGG) 2/3 (HR 2.966; p 0.003) and BGG 4/5 (HR 3.122; p = 0.022) pathologic grade group 4/5 (HR 3.257; p = 0.001), pT3b (HR 2.900; p = 0.003), and non-focal PSM (HR 2.287; p = 0.012). Surgeon volume was not a predictor of BCR (p = 0.253). High surgeon volume is an independent factor that lowers the risk of focal PSM. Surgeon volume does not affect non-focal PSM and BCR. Negative as well as focal PSM are not associated with BCR.

Prostate volume index and prostatic chronic inflammation have an effect on tumor load at baseline random biopsies in patients with normal DRE and PSA values less than 10 ng/ml: results of 564 consecutive cases.

BACKGROUND: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume (CTZV) to the peripheral zone volume (PZV), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) load in patients presenting with normal digital rectal exam (DRE) and prostate-specific antigen (PSA) ⩽ 10 ng/ml at baseline random biopsies. METHODS: Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core transperineal randomized biopsies. We considered small and high PCA load patients with no more than three (limited tumor load) and greater than three (extensive tumor load) positive biopsy cores, respectively. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing different multivariate models. RESULTS: 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases, respectively. On multivariate analysis, PVI and PCI were independent predictors of the risk of detecting limited or extensive tumor load. The risk of detecting extensive tumor load at baseline biopsies was increased by PSAD above the median and third quartile as well as PVI ⩽ 1 [odds ratio (OR)=1.971] but decreased by PCI (OR=0.185; 95% CI: 0.088-0.388). CONCLUSIONS: Higher PVI and the presence of PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ⩽ 10 ng/ml at baseline random biopsy. In this subset of patients, a PVI ⩽ or >1 is able to differentiate patients with PCA or PCI.

High surgeon volume and positive surgical margins can predict the risk of biochemical recurrence after robot-assisted radical prostatectomy.

BACKGROUND: The aim of this study was to determine whether any clinical factors are independent predictors of positive surgical margins (PSM), and to assess the association of PSM and biochemical recurrence (BR) after robot-assisted radical prostatectomy (RARP). METHODS: The population included cases with negative surgical margins (control group) and patients with PSM (study group). Tumor grade was evaluated according to the International Society of Urologic Pathology (ISUP) system. A logistic regression model assessed the independent association of factors with the risk of PSM. The risk of BR was assessed by Cox's multivariate proportional hazards. RESULTS: A total of 732 consecutive patients were evaluated. Extend pelvic lymph node dissection (ePLND) was performed in 342 cases (46.7%). Overall, 192 cases (26.3%) had PSM. The risk of PSM was positively associated with the percentage of biopsy positive cores (BPC; odds ratio, OR = 1.012; p = 0.004), extracapsular extension (pT3a; OR=2.702; p < 0.0001), invasion of seminal vesicle (pT3b; OR = 2.889; p < 0.0001), but inversely with body mass index (OR = 0.936; p = 0.021), and high surgeon volume (OR = 0.607; p = 0.006). Independent clinical factors associated with the risk of BR were baseline prostate-specific antigen (PSA; hazard ratio, HR = 1.064; p = 0.004), BPC (HR = 1.015; p = 0.027), ISUP biopsy grade group (BGG) 2/3 (HR = 2.966; p = 0.003), and BGG 4/5 (HR = 3.122; p = 0.022). Pathologic factors associated with the risk of BR were ISUP group 4/5 (HR = 3.257; p = 0.001), pT3b (HR = 2.900; p = 0.003), and PSM (HR = 2.096; p = 0.045). CONCLUSIONS: In our cohort, features related to host, tumor, and surgeon volume are associated with the risk of PSM, which is also an independent parameter predicting BR after RARP. The surgical volume of the operating surgeon is an independent factor that decreases the risk of PSM, and, as such, the risk of BR.