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.

Predictors of complications occurring after open and robot-assisted prostate cancer surgery: a retrospective evaluation of 1062 consecutive patients treated in a tertiary referral high volume center.

To investigate factors associated with the risk of major complications after radical prostatectomy (RP) by the open (ORP) or robot-assisted (RARP) approach for prostate cancer (PCa) in a tertiary referral center. 1062 consecutive patients submitted to RP were prospectively collected. The following outcomes were addressed: (1) overall postoperative complications: subjects with Clavien-Dindo System (CD) one through five versus cases without any complication; (2) moderate to major postoperative complications: cases with CD < 2 vs. ≥ 2, and 3) major post-operative complications: subjects with CDS CD ≥ 3 vs. < 3. The association of pre-operative and intra-operative factors with the risk of postoperative complications was assessed by the logistic regression model. Overall, complications occurred in 310 out of 1062 subjects (29.2%). Major complications occurred in 58 cases (5.5%). On multivariate analysis, major complications were predicted by PCa surgery and intraoperative estimated blood loss (EBL). ORP compared to RARP increased the risk of major CD complications from 2.8 to 19.3% (OR = 8283; p < 0.0001). Performing ePLND increased the risk of major complications from 2.4 to 7.4% (OR = 3090; p < 0.0001). Assessing intraoperative blood loss, the risk of major postoperative complications was increased by BL above the third quartile when compared to subjects with intraoperative blood loss up to the third quartile (10.2% vs. 4.6%; OR = 2239; 95%CI: 1233-4064). In the present cohort, radical prostatectomy showed major postoperative complications that were independently predicted by the open approach, extended lymph-node dissection, and excessive intraoperative blood loss.

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.

Endogenous testosterone density as ratio of endogenous testosterone levels on prostate volume predicts tumor upgrading in low-risk prostate cancer.

OBJECTIVES: To evaluate preoperative endogenous testosterone (ET) density (ETD), defined as the ratio of ET on prostate volume, and tumor upgrading risk in low-risk prostate cancer (PCa). MATERIALS AND METHODS: From November 2014 to December 2019, 172 low-risk patients had ET (nmol/L) measured. ETD, prostate-specific antigen density (PSAD) and the ratio of percentage of biopsy positive cores (BPC) to prostate volume (PV), defined as BPC density (BPCD), were evaluated. Associations with tumor upgrading in the surgical specimen were assessed by statistical methods. RESULTS: Overall, 121 patients (70.3%) had tumor upgrading, which was predicted by BPCD (odds ratio, OR = 4.640; 95% CI 1.903-11.316; p = 0.001; overall accuracy: 70.3%). On multivariate analysis, tumor upgrading and clinical density factors related to each other for BPCD being predicted by ETD (regression coefficient, b = 0.032; 95% CI 0.021-0.043; p < 0.0001), PSAD (b = 1.962; 95% CI 1.067-2.586; p < 0.0001) and tumor upgrading (b = 0.259; 95% CI 0.112-0.406; p = 0.001). According to the model, as BPCD increased, ETD and PSAD increased, but the increase was higher for upgraded cases who showed either higher tumor load but significantly lower mean levels of either ET or PSA. CONCLUSIONS: As ETD increased, higher tumor loads were assessed; however, in upgraded patients, lower ET was also detected. ETD might stratify low-risk disease for tumor upgrading features.

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.

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.

Current clinical management of renal and perinephric abscesses: a literature review.

Renal and perinephric abscesses are rare but very severe conditions resulting from infections in or surrounding the kidneys. Symptoms and imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI) and renal ultrasound (US) of higher quality have led to an early diagnosis that is very important for patients' prognosis. The best clinical approach to manage this disease is still debated. Antibiotic therapy represents the usual treatment of small renal abscesses. This management can be insufficient in case of larger renal abscesses requiring percutaneous or surgical drainage. Perinephric abscesses most commonly need invasive maneuvers. We conducted a literature review to clearly define the most recommended clinical managements for all cases of renal and perinephric abscesses.

Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer and subsequent cluster selection of the patient population undergoing standard radical prostatectomy.

AIM: A preceding exploratory analysis has shown that follicle-stimulating hormone (FSH) was significantly correlated to and predicted by prostate-specific antigen (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of initial diagnosis of prostate cancer in an operated population clustered according to the FSH/PSA ratio. PATIENTS AND METHODS: The study included 93 patients who underwent standard radical prostatectomy. Age, percentages of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH, prolactin hormone (PRL), total testosterone (TT), free testosterone (FT), estradiol (ESR) and PSA were the continuous variables. Category variables were pT and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was clustered according to the FSH/PSA ratio which was computed from empirical data and then ranked for clustering the population as groups A (range 0.13 ≤ FSH/PSA ≤ 0.20), B (range 0.20 < FSH/PSA ≤ 0.50), C (range 0.50 < FSH/PSA ≤ 0.75), D (range 0.75 < FSH/PSA ≤ 1.00), E (range 1.00 < FSH/PSA ≤ 1.25), F (range 1.25 < FSH/PSA ≤ 2.00), G (range 2.00 < FSH/PSA ≤ 2.25), H (range 2.25 < FSH/PSA ≤ 6.40) and I (range 6.40 < FSH/ PSA ≤ 19.40). The model was assessed by simple linear regression analysis and differences between the groups were investigated by analysis of variance (ANOVA) for continuous variables and by contingency tables for category variables. RESULTS: FSH was significantly correlated to and predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p < 0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p = 0.001). Also, clusters (A-I) differed significantly for mean values of FSH (p < 0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed significant different frequency distributions of pGPI (p = 0.02), pGPII (p = 0.0002) and bGPI (p = 0.04). CONCLUSION: The ranking FSH/PSA ratio significantly clustered, along the PTP axis, an operated population diagnosed with prostate cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters expressing different levels of hormonal disorder along the PTP axis and prognostic potential with different risks of progression. As a theory, in the current advancing world, the ranking FSH/PSA model might be considered as an interesting and effective tool for prostate cancer study as well as individualized, risk-adapted approaches of the disease. However, confirmatory studies are needed.

Accuracy of preoperative endo-rectal coil magnetic resonance imaging in detecting clinical under-staging of localized prostate cancer.

OBJECTIVES: To assess the accuracy of intra-rectal coil magnetic resonance imaging (ER-MRI) for staging early prostate cancer (EPC). MATERIALS AND METHODS: ER-MRI was performed with the Magnetom Symphony 1.5 Tesla system. ER-MRI and pathology findings were statistically correlated. RESULTS: One hundred and fifty-four consecutive patients underwent radical prostatectomy (RRP) for EPC (cT1c-2 Nx M0). An average age was 66, mean PSA 11.04 µg/L (median 7.33 µg/L) and mean pathologic Gleason score 6. Pathology detected 97 out of 154 patients (63 %) as EPC and 57 cases (37 %) as extra-prostate extension (EPED) (pT3) with extra-capsular extension (ECE) (pT3a) in 41 (27 %) and seminal vesicle invasion (SVI) (pT3b) in 16 (10 %). ER-MRI staged 100 patients (65 %) as cT2 and 54 (35 %) as EPED with ECE in 37 cases (24 %) and SVI in 17 (11 %). ER-MRI sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy resulted respectively 0.78, 0.96, 0.86, 0.92, 0.91 for ECE as well as 0.88, 0.98, 0.82, 0.99 and 0.97 for SVI. CONCLUSION: ER-MRI was effective in detecting preoperative EPC under-staging. In the next future, multi-parametric 3-Tesla ER-MRI will be the procedure for diagnosing, staging and following-up prostate cancer patients.

Investigative clinical study on prostate cancer part IX and X: estradiol and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

AIM: To evaluate estradiol (E(2)) physiopathology along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer (PC) and subsequent cluster selection of the patient population. PATIENTS AND METHODS: Records of the diagnosed (n=105) and operated (n=91) patients were retrospectively reviewed. Age, percentage of positive cores at-biopsy (P+), biopsy Gleason score (bGS), E(2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free-testosterone (FT), prostate-specific antigen (PSA), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi), clinical stage (cT), biopsy Gleason pattern (bGP) and pathology stage (pT), were the investigated variables. None of the patients had previously undergone hormonal manipulations. E(2) correlation and prediction by multiple linear regression analysis (MLRA) was performed. At diagnosis, the log E(2)/log bGS ratio clustered the population into groups A (log E(2)/log bGS ≤ 2.25), B (2.25

Investigative clinical study on prostate cancer part VIII: prolactin hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

AIM: To evaluate the prolactin hormone (PRL) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer and the subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables. PATIENTS AND METHODS: Ninety-two operated prostate cancer patients were retrospectively reviewed. No patient had previously received hormonal treatment. The investigated variables included PRL, follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), total prostate specific antigen (PSA), percentage of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi) and age. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population and clustered according to pT (2a/b, 3a, 3b/4) status. The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5< log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+ >2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model and analysis of variance was performed for assessing significant differences between the groups. RESULTS: PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b). Interestingly, PRL was independently predicted by LH (p=0.03) and FSH, TT, FT, PSA, bGS, pGS, V+, Wi and age (all at p=0.01) in advanced stage-disease (pT3b/4). V+ was also significantly correlated (r=0.47) and predicted by P+ (p<0.0001) in the prostate cancer population. PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10)PRL/V+ ratio in group A (p=0.008), B (p<0.0001) and C (p<0.0001). Moreover, the three groups had significantly different mean values of PRL (p<0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p<0.0001), Wi (p=0.03), bGS (p=0.008), pGS (p=0.003); also, groups A, B and C had significant different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions. CONCLUSION: At diagnosis, in an operated prostate cancer population, PRL was significantly correlated and independently predicted along the pituitary testis prostate axis in high-stage disease; V+ was also significantly correlated and predicted by P+. Because of the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10)PRL/V+ ratio into groups A, B and C that, in theory, might be models with prognostic potential and clinical applications in the prostate cancer population. However, confirmatory studies are needed.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57

Investigative clinical study on prostate cancer part VII: prolactin and the pituitary-testis-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate prolactin (PRL) physiopathology along the pituitary-testis-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: The study involved 100 individuals diagnosed with prostate cancer. Age, percentage of positive cores at transrectal ultrasound scan biopsy (P+), biopsy Gleason score (BGS), PRL, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received hormonal manipulations. Correlation and multiple linear regression analysis of the the variables along the pituitary-testis-prostate cancer axis was performed. The prostate cancer population was clustered according to the PRL/P+ ratio into group A (4.20≤PRL/P+ ≤20), B (20

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.

Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy.

OBJECTIVES: To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. PATIENTS AND METHODS: 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. RESULTS: The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) µg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). CONCLUSIONS: Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: 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). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS.

Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients.

OBJECTIVES: To show that prostate cancer biology is related to serum levels of both free testosterone (FT) and prostate-specific antigen (PSA), that PSA level is linearly related to FT and that the PSA to FT ratio may be considered as the growth rate parameter expressing cancer phenotype biology. MATERIALS AND METHODS: The study includes 135 consecutive patients diagnosed with prostate cancer. Pretreatment simultaneous serum samples for analyzing total testosterone (TT), FT and total PSA levels were obtained. The study was assessed according to a multidimensional approach of the five continuous variables including TT, FT, PSA, AGE and percentage of positive biopsies (=P+). The all sets of data were considered as one--sample with no groupings among the observations. Multivariate analysis included factor analysis (FA) and principal component analysis (PCA). Multivariate inferential statistics for comparing different groups of patients according to the PSA to free testosterone ratio (PSA/FT) included Hotteling's multivariate two-sample T²-Test for comparing two mean vectors as well as Box's M-Test with the chi-square approximation for comparing multiple covariance matrices when patients were sampled in more than two groups. RESULTS: Factor analysis showed the two natural grouping of variables, FT-TT and PSA-P+. PCA assessed FT and PSA as the two variables with large variances having a notable influence on the first two principal components. Multiple linear regression analysis showed that all the income variables, except age, significantly predicted the PSA/FT ratio. Patients were first sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20) and group 2 (PSA/FT > 0.20), and Hotteling's multivariate two sample T²-Test was significant (P < 0.01). Patients were then sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20), group 2 (PSA/FT > 0.20 and ≤ 0.40), and group 3 (PSA/FT > 0.40), and Box's M-Test comparing the covariance matrices of the 3 groups differed significantly (P < 0.001). Finally, patients were sampled according to the PSA/FT ratio in 6 groups, and Box's M-Test was again significant (P < 0.001). CONCLUSIONS: The PSA to FT ratio is the growing rate parameter expressing different biology patterns and assessing different groups of prostate cancer patients. In our opinion, the results of the present study might have wide applications in understanding, assessing and planning prostate cancer studies including basic science, screening, assessing risk of the disease, predicting disease stage as well natural history after a planned treatment involving biochemical recurrence, progression, hormone refractory prostate cancer and disease-specific survival.