Preoperative endogenous total testosterone predicts prostate cancer progression: results in 580 consecutive patients treated with robot assisted radical prostatectomy for clinically localized disease.

PURPOSE: To test the role of endogenous total testosterone (ETT) as a predictor of prostate cancer (PCa) progression in patients treated with robot assisted radical prostatectomy for clinically localized disease. METHODS: Between November 2014 and December 2019, 580 consecutive patients were evaluated. Preoperative ETT levels were classified as ≤ 350 ng/dL vs. > 350 ng/dL. The associations between ETT levels and the risk of PCa progression, defined as any event of biochemical recurrence and/or local recurrence and/or distant metastases, or other clinical and pathological factors were evaluated by regression analyses. RESULTS: Preoperative ETT levels resulted ≤ 350 ng/dL in 173 (29.8%) patients. Disease progression occurred in 101 (17.1%) cases. Progressing patients were more likely to present with PSA levels > 10 ng/mL, as well as with unfavorable tumor grade (ISUP 4-5) and stage (pT3b) at final pathology, but less likely to have ETT levels ≤ 350 ng/mL. On clinical multivariable Cox regression models, ETT ≤ 350 ng/mL exhibited a statistically significant protective effect on tumor progression (hazard ratio: 0.57, p = 0.013). Subjects presenting with ETT levels ≤ 350 ng/mL were less likely to harbor ISUP 4-5 tumor grade either at biopsy (odds ratio [OR]: 0.46, p = 0.028) or final pathology (OR: 0.45, p = 0.032). CONCLUSIONS: At PCa diagnosis, ETT, which associates with ISUP tumor grade, is an independent predictor of disease progression. Accordingly, as ETT decreases to levels ≤ 350 ng/dL, the risk of unfavorable tumor grade decreases, and a more favorable prognosis is expected. Preoperative ETT levels may allow further patient stratification along prognostic risk groups.

American Society of Anesthesiologists (ASA) physical status system predicts the risk of postoperative Clavien-Dindo complications greater than one at 90 days after robot-assisted radical prostatectomy: final results of a tertiary referral center.

To test the hypothesis of an association between the American Society of Anesthesiologists (ASA) physical status classification system and the risk of 90-days postoperative complications after robot-assisted radical prostatectomy (RARP), graded using the Clavien-Dindo classification system (CDS). In a period ranging from January 2013 to October 2020, 1143 patients were evaluated. ASA classification was computed by trained anesthesiologists. Postoperative complications at 90 days after RARP were grouped as greater than one (CDS between 2 and 4a) versus up to one (CDS between 0 and 1). The risk association was computed using logistic regression models. According to ASA physical status classification system, patients were distributed as follows: 102 (8.9%) ASA 1, 934 (81.7%) ASA 2, and 107 (9.4%) ASA 3. Overall, 90-days postoperative complications occurred in 277 (24.2%) cases, of which 137 (12%) were graded as CDS 1 vs. 105 (9.2%) CDS 2 vs. 17 (1.5%) CDS 3a vs. 15 (1.3%) CDS 3b vs. 3 (0.3%) CDS 4a. ASA 2 and 3 patient categories were more likely to have 90-days postoperative complications CDS > 1 (12.5% and 16.8%, respectively) compared to ASA 1 patients (4.9%). The risk association was stronger for ASA 3 (odds ratio, [OR]: 4.085; 95%CI: 1.457-11.455; p = 0.007) than for ASA 2 (OR: 2.907; 95%CI: 1.106-7.285; p = 0.023) patient categories. After adjustment for clinical, pathological, and perioperative covariates, including pelvic lymph node dissection (performed vs. not performed), either ASA 2 or 3 categories remained independent predictors of 90-days postoperative complications CDS > 1. The risk of 90-days postoperative complications CDS > 1 after RARP increased as the ASA physical status deteriorated independently by performing or not an extended pelvic lymph node dissection. In the ASA 3 patients category, RARP should be performed at tertiary referral centers to safely manage the risk of postoperative complications.

Severe systemic disease of the American Society of Anesthesiologists' (ASA) physical status system classification associated with delayed length of hospital stay in 1329 consecutive patients treated with radical prostatectomy for clinical prostate cancer.

BACKGROUND: The investigate the associations of the ASA physical status system with clinical, pathological, and perioperative features of prostate cancer (PCa) patients treated with radical prostatectomy (RP) that eventually associated with pelvic lymph node dissection (PLND). METHODS: We performed a retrospective analysis of prospective collected data from January 2013 to October 2020, including1329 patients. The ASA system was preoperatively assessed for each patient. Evaluated clinical factors were grouped as preoperative, perioperative, and pathological and were statistically associated with the ASA system. Continuous variables were represented as medians with relative interquartile ranges (IQR) and categorical factors were assessed as frequencies (percentages). Associations and risk of each ASA Class with population features were assessed by the multinomial logistic regression model (univariate and multivariate analysis). All tests were two-sided with P<0.05 considered to indicate statistical significance. RESULTS: Postoperative complications at discharge occurred in 27.2%. The distribution of the ASA physical status system was as follows: ASA I 108 patients (8.1%), ASA II 1081 subjects (81.3%) and ASA III 140 cases (10.5%). Median length of hospital state (LOHS) was the same for ASA groups I and II (4 days), but longer (5 days) for the ASA group III. On MVA, the risk of delayed hospital stay was associated only with ASA III patients and was independent from age and BMI. Clavien-Dindo complications greater than 2 did not show any independent association with the ASA system. CONCLUSIONS: The ASA preoperative physical status system predicted the likelihood of longer LOHS.

Endogenous testosterone density is an independent predictor of pelvic lymph node invasion in high-risk prostate cancer: results in 201 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection.

OBJECTIVE: To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with radical prostatectomy (RP) and staged with extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: ETD was evaluated as the ratio of endogenous testosterone (ET) on prostate volume (PV). HR-PCa was assessed according to the European Association of Urology (EAU) system. The association of ETD and other routinely clinical factors (BPC: percentage of biopsy positive cores; PSA: prostate specific antigen; ISUP: tumor grade system according to the International Society of Urologic Pathology; cT: tumor clinical stage) with the risk of PLNI was assessed by the logistic regression model. RESULTS: Overall, 201 out of 805 patients (24.9%) were classified HR and PLNI occurred in 42 subjects (20.9%). On multivariate analysis, PLNI was independently predicted by BPC (OR 1.020; 95% CI 1.006-1.035; p = 0.019), ISUP > 3 (OR 2.621; 95% CI 1.170-5.869; p = 0.019) and ETD (OR 0.932; 95% CI 0.870-0.999; p = 0.045). After categorizing continuous clinical predictors, the risk of PLNI was independently increased by ETD up to the median (OR 2.379; 95% CI 1.134-4.991; p = 0.022), BPC > 50% (OR 3.125; 95% CI 1.520-6.425; p = 0.002) as well as by ISUP > 3 (OR 2.219; 95% CI 1.031-4.776; p = 0.042). CONCLUSIONS: As ETD measurements decreased, patients were more likely to have PLNI. In HR disease with PLNI, the influence of PCa on ETD should be addressed by higher level studies.

Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection.

OBJECTIVE: To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N = 0) or with one (N = 1) or more than one metastatic node (N > 1). The risk of multiple pelvic lymph node metastasis (N > 1, mPLNM) was assessed by comparing it to the other two groups (N > 1 vs. N = 0 and N > 1 vs. N = 1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT > 1) and tumor grade group greater than two (ISUP > 2). RESULTS: Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N = 1 and 31 (5%) with N > 1. On multivariate analysis, ET was inversely associated with the risk of N > 1 when compared to both N = 0 (odds ratio, OR 0.997; CI 0.994-1; p = 0.027) as well as with N = 1 cases (OR 0.994; 95% CI 0.989-1.000; p = 0.015). CONCLUSIONS: In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

Clinical Factors Predicting and Stratifying the Risk of Lymph Node Invasion in Localized Prostate Cancer.

PURPOSE: The study aimed to investigate clinical factors associating with occult lymph node micrometastases (pN1 disease) in a contemporary cohort of organ-confined prostate cancer (PCA) patients staged as cN0. MATERIALS AND METHODS: The study evaluated 184 consecutive patients. Associations of clinical factors with pN1 disease were assessed by multivariate logistic regression analysis. RESULTS: Lymph node invasion was detected in 33 cases (17.9%). Independent factors associating with pN1 status were prostate specific antigen (PSA; OR 1.054; p = 0.004), percentage of positive biopsy cores (PPC; OR 1.030; p = 0.013), and biopsy Gleason pattern (bGP) >4 + 3 (OR 3.666; p = 0.004). A clinical model predicting the risk of pN1 disease identified 4 prognostic groups of pN1 disease. CONCLUSIONS: In a contemporary cohort of PCA patients, lymph node invasion was detected in 17.9% of cases. An independent clinical disease showed that the risk of lymph node invasion was directly proportional to PPC and more stratification of the risk of pN1 disease was operated by PSA and BGP. The model allowed the stratification of the patient population in 4 groups and showed that the risk of lymph node invasion progressively increased as the risk group ranked from 1 to 4.

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.

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 < 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.

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer.

BACKGROUND: Chronic inflammatory infiltrate (CII) might be involved in prostate cancer (PCA) and benign hyperplasia (BPH); however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. OBJECTIVE: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. DESIGN, SETTING, AND PARTICIPANTS: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years) and PSA (ug/l); moreover, CII+, glandular atrophy (GA+), glandular hyperplasia (GH+), prostate Intraepithelial neoplasm (PIN+), atypical small acinar cell proliferation (ASAP+) and PCA positive cores (P+) were evaluated as categorical and continuous (proportion of positive cores). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of CII+ and PCA risk were assessed by statistical methods. RESULTS AND LIMITATIONS: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8) resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26) and HGPCA (P = 0.0005; OR = 0.05). Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. CONCLUSIONS: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in PCA carcinogenesis remains controversial and needs further research.

Investigative clinical study on prostate cancer part IV: exploring functional relationships of total testosterone predicting free testosterone and total prostate-specific antigen in operated prostate cancer patients.

OBJECTIVES: To explore, in operated prostate cancer patients, functional relationships of total testosterone (tt) predicting free testosterone (ft) and total PSA. PATIENTS AND METHODS: 128 operated prostate cancer patients were simultaneously investigated for tt, ft and PSA before surgery. Patients were not receiving 5α-reductase inhibitors, LH-releasing hormone analogues and testosterone replacement treatment. Scatter plots including ft and PSA versus tt were computed in order to assess the functional relationship of the variables. Linear regression analysis of tt predicting ft and PSA was computed. RESULTS: tt was a significant predictor of the response variable (ft) and different subsets of the patient population were assessed according to the ft to tt ratio. PSA was related to tt according to a nonlinear law. tt was a significant predictor of PSA according to an inversely nonlinear law and different significant clusters of the patient population were assessed according to the different constant of proportionality computed from experimental data. CONCLUSIONS: In our prostate cancer population, ft was significantly predicted by tt according to a linear law, and the ft/tt ratio was a significant parameter for assessing the different clusters. Also, tt was a significant variable predicting PSA by a nonlinear law and different clusters of the patient population were assessed by the different constants of proportionality. As a theory, we explain the nonlinear relation of tt in predicting PSA as follows: (a) the number of androgen-independent prostate cancer cells increases as tumor volume and PSA serum levels rise, (b) the prevalence of androgen-independent cells producing a substance which inhibits serum LH, and (c) as a result lower levels of serum tt are detected.

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

OBJECTIVES: Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. PATIENTS AND METHODS: The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. RESULTS: Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. CONCLUSIONS: According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed.

Vesicouterine fistulas following cesarean section: report on a case, review and update of the literature.

Herein we report on 1 more case of vesicouterine fistula following cesarean section with review and update of the literature concerning this unusual topic. The disease presented with vaginal urinary leakage, cyclic hematuria and amenorrhea. The fistula was successfully repaired by delayed surgery. Actually, all over the world the prevalence of the disease is increasing for the frequent use of the cesarean section. Fistulas may develop immediately after a cesarean section, manifest in the late puerperium or occur after repeated procedures. Spontaneous healing is reported in 5% of cases. Vesicouterine fistulas present with vaginal urinary leakage, cyclic hematuira (menouria), amenorrhea, infertility, and first trimester abortions. The diagnosis is ruled out by showing the fistulous track between bladder and uterus as well as by excluding other more frequent urogenital fistulas. The disease treatment options include conservative treatment as well as surgical repair. Rarely, patients refuse any kind of treatment because of the benignity of symptoms and prognosis of the disease. Conservative management by bladder catheterization for at least 4-8 weeks is indicated when the fistula is discoveredjust after delivery since there is good chance for spontaneous closure of the fistulous track. Hormonal management should be tried in women presenting with Youssef's syndrome. Surgery is the maninstay and definitive treatment of vesicouterine fistulas after cesarean section. Patients scheduled for surgery should undergo pretreatment of urinary tract infections. Surgical repair of vesico-uterine fistulas are performed by different approaches which include the vaginal, transvesical-retroperitoneal and transperitoneal access which is considered the most effective with the lowest relapse rate. Recently, laparoscopy has been proposed as a valid option for repairing vesicouterine fistulas. The endoscopic treatment may be effective in treating small vesicouterine fistulas. The pregnancy rate after repair is 31.25% with a rate of term deliveries of 25%. The disease may be prevented by emptying the bladder as well as by carefully dissecting the lower uterine segment. It is advisable that after vesicouterine fistula repair delivery should be performed by repeating a cesarean section since the risk of fistula recurrence. Usually, vesicouterine fistulas are diagnosed postoperatively. As a result, at least 95% of patients will undergo another operation for repairing the fistula. In the meantime they are bothered by related symptoms which impair their quality of life. As far as we are concerned intraoperative diagnosis is the gold standard in detecting vesicouterine fistulas for allowing immediate repair. We propose intraoperative sonography by the transvaginal (or transrectal) route for the Foley transurethral catheter producing bloody urine, for suspecting bladder injury while dissecting the uterine lower segment and for monitoring patients who already had had vesicouterine fistula repair. As a result patients will avoid the familial and social problems related to the disease as well another operation. Moreover, ultrasound Doppler examination may help in better investigating and understanding the pathophysiology of vesicouterine fistulas.