Unravelling the Role of P300 and TMPRSS2 in Prostate Cancer: A Literature Review.

Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The TMPRSS2:ERG fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with TMPRSS2:ETS (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.

Proteomic Analysis of Prostate Cancer FFPE Samples Reveals Markers of Disease Progression and Aggressiveness.

Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy, which might not represent the exact degree of PCa risk. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Comparative analysis of 86 PCa samples among grade groups 1-5 identified 301 significantly altered proteins. Additional analysis based on biochemical recurrence (BCR; BCR+ n = 14, BCR- n = 51) revealed 197 significantly altered proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins (NPM1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness. Notably, all seven proteins were significantly associated with progression in Prostate Cancer Transcriptome Atles (PCTA) and NPM1NPM1, UQCRH, and VCAN were further validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. UQCRH levels were also associated with poorer 5-year survival. Our study provides valuable insights into the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.

Prediction of post radical nephrectomy complications based on patient comorbidity preoperatively.

OBJECTIVES: Comorbidity along with tumor and patient characteristics is taken into account when deciding for the surgical treatment of renal cell carcinoma (RCC). Comorbidity has also been used as an independent predictive factor for postoperative complications of several major urological procedures including radical nephrectomy for RCC. The aim of the present study was to objectively evaluate the association between comorbidity and postoperative complications after radical nephrectomy for RCC, using standardized systems to grade both comorbidity and severity of postoperative complications. MATERIALS AND METHODS: Clinicopathological data of 171 patients undergoing open radical nephrectomy for lesions suspected of RCC were prospectively recorded for a period of 3 years. Comorbidity was scored using the Charlson Comorbidity Index (CCI) while postoperative complications were graded according to the Clavien-Dindo system. RESULTS: Patients were predominantly males (59.1%); their age ranged from 35 to 88 years (mean ± SD: 63.6 ± 11.9 yrs) with 50.8% of them being ≤ 65 yrs. CCI ranged from 0 to 8 with the majority (85.3%) scoring ≤ 2. The procedure was uncomplicated in 57.3% cases; 10 patients suffered major (grade III/IV) complications and 4 patients died within the 40 days postoperative period. CCI correlated with the manifestation of any postoperative complication, Clavien ≥ 1, OR (95% CI): 1.47 (1.09-1.96), p = 0.011 and the occurrence of severe complications, Clavien > 2. OR (95% CI): 1.29 (1.01-1.63), p = 0.038. CONCLUSIONS: The present prospective study showed that considerable complications occur in patients with major comorbidities. CCI is easily calculated and should be incorporated in preoperative consultation especially in cases of elder patients with severe comorbidity and favorable tumor characteristics where less invasive interventions or even active surveillance could be applied.

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. PATIENTS AND METHODS: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. RESULTS: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. CONCLUSION: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

Detecting Novel Urine Biomarkers for the Early Diagnosis of Prostate Cancer: Platelet Derived Growth Factor-BB as a Possible New Target.

INTRODUCTION: Although the prostate specific antigen revolutionized the diagnosis of prostate cancer (PCa), it has its limitations. We prospectively examined the potential use of the platelet-derived growth factor-BB (PDGF-BB) as a urine biomarker for the early diagnosis of PCa. MATERIALS AND METHODS: The urine samples of 118 patients were collected after a prostatic massage and all the patients subsequently underwent ultrasound-guided transrectal biopsy. PDGF-BB was detected in the urine by enzyme-linked immunosorbent assay. RESULTS: Patients with PCa had greater levels of prostate specific antigen and PDGF-BB. Receiver operating characteristic curve analysis showed that the optimal cut-of of PDGF-BB for the prediction of PCa was 1,504.9 with a sensitivity of 60% and a specificity of 51.3%. For a 100 unit increase in PDGF-BB, the likelihood for PCa increased about 4%. CONCLUSION: PDGF-BB showed a significant predictive ability for PCa. Detection of PDGF-BB in urine with Elisa was easy and improved our diagnostic accuracy in the diagnosis of PCa.

Hyaluronic acid and hyaluronidase as possible novel urine biomarkers for the diagnosis of prostate cancer.

The goal of the study is to examine the possible use of HA (hyaluronic acid) and HAase (hyaluronidase) as novel urine biomarkers for the early diagnosis for prostate cancer (Pca). After a prostatic massage, the urine of 118 high-risk patients for Pca was collected, and the patients were submitted to ultrasound-guided transrectal biopsy. HA and HAase were detected and analyzed with Enzyme-Linked Immunosorbent Assay, and a statistical analysis of the urine levels of the two biomarkers according to the histology results was performed. HAase and HA were independently associated with Pca, and both HAase and HA showed significant predictive ability for prostate cancer. With an optimal cut-off point of 183.71 HAase had 70% sensitivity maintaining at the same time a 55.2% specificity, while the optimal cut-off point for HA was 50.13 with 65% sensitivity and 53.9% specificity. Patients with HAase more than 183.71 ng/ml had 3.67 times greater likelihood for prostate cancer and Patients with HA more than 50.13 ng/ml had 2.31 times greater likelihood for prostate cancer. The need of novel biomarkers that will improve the efficacy of PSA is urgent. HAase and HA showed significant predictive ability for prostate cancer and were independently associated with Pca, and greater levels were associated with greater odds for prostate cancer. To Our Knowledge, this is the first study referring to the detection of HAase and HA as potential urine biomarkers for the early diagnosis of Pca.

Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.

PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.

Downregulated KLK13 expression in bladder cancer highlights tumor aggressiveness and unfavorable patients' prognosis.

PURPOSE: Despite recent research advantages on the molecular and subcellular background, bladder cancer (BlCa) remains a clinically neglected malignancy. This is strongly reflected by the generic approach of disease diagnosis and management. Additionally, patients' prognosis became a rather demanding task due to the great disease heterogeneity. Here, we aimed to evaluate, for the first time, the clinical value of KLK13 in BlCa. METHODS: A total of 279 bladder specimens (137 tumors, 107 adjacent normal tissues and 35 healthy samples) were included. Total RNA was extracted, reverse transcribed, and KLK13 expression was assessed by quantitative real-time PCR. RESULTS: KLK13 expression is significantly increased in bladder tumors compared to normal adjacent epithelium. However, reduced KLK13 expression is correlated with disease aggressiveness, including higher tumor stage and grade, and high-risk TaT1 tumors according to the EORTC stratification. Moreover, Kaplan-Meier and Cox regression analysis highlighted the prognostic value of the reduced KLK13 expression for the prediction of TaT1 patients' recurrence and shorter disease-free survival following TURBT. Finally, the combination of KLK13 expression with EORTC-risk stratification results to an improved prediction of TaT1 patients' outcome. CONCLUSION: This first clinical study of KLK13 in BlCa reveals its deregulated expression in bladder tumors and highlights KLK13 as a promising marker for improving TaT1 patients' prognosis following treatment.

Role of coagulation factors in urological malignancy: A prospective, controlled study on prostate, renal and bladder cancer.

OBJECTIVES: To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. METHODS: This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal (n = 44), prostate (n = 56) and bladder cancer (n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. RESULTS: Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). CONCLUSIONS: The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events.

In the search of novel urine biomarkers for the early diagnosis of prostate cancer. Intracellular or secreted proteins as the target group? Where and how to search for possible biomarkers useful in the everyday clinical practice.

OBJECTIVE: To search which category of proteins can be detected in urine in order to examine subsequently its ability to improve our accuracy for the diagnosis of Prostate Cancer (PCa) as biomarkers in clinical useful fluids like urine and serum. Material and method(s): Urine samples of 127 patients were obtained after a vigorous transrectal prostatic massage to both lobes. The patients were considered to have a high risk for PCa according to their PSA (> 4 ng/ml), their digital rectal examination (DRE) (positive for suspicious prostatic lesions) or to their abnormal PSA kinetics (PSA velocity (PSAV > 0.75 ng/mL). All patients subsequently were subjected to an extended 10-core per prostatic lobe TRUS-b (total 20 prostatic samples). The proteins that were chosen to be detected in the urine samples with Western-blot, as possible biomarkers, were Glutathione peroxidase 3 precursor (GPx3), Cofilin-1 (CFL1), Heat shock protein-90ß (HSP 90ß), Zinc alpha 2-glycoprotein (ZAG) and secreted protein acidic and rich in cysteine (SPARC).These proteins have been detected previously in the prostatic tissue by proteomics proving their discriminative ability between patients with prostate cancer and benign prostatic hyperplasia. RESULT(S): From the five proteins, only the secreted Zinc alpha 2-glycoprotein was detected in urine showing a promising ability in the improvement of our diagnostic accuracy for the early diagnosis of prostate cancer. CONCLUSIONS: From various categories of proteins that have already been detected in the tissue of prostate by proteomics, only secreted protein Zinc alpha 2-glycoprotein showed a clear signal in the urine, proving its discriminative potential for the early diagnosis of PCa.

Metastasis to sartorius muscle from a muscle invasive bladder cancer.

Bladder cancer constitutes the ninth most common cancer worldwide and approximately only 30% of cases are muscle invasive at initial diagnosis. Regional lymph nodes, bones, lung, and liver are the most common metastases from bladder cancer and generally from genitourinary malignancies. Muscles constitute a rare site of metastases from distant primary lesions even though they represent 50% of total body mass and receive a large blood flow. Skeletal muscles from urothelial carcinoma are very rare and up to date only few cases have been reported in the literature. We present a rare case of 51-year-old patient with metastases to sartorius muscle 8 months after the radical cystectomy performed for a muscle invasive bladder cancer.

Castrati singers: surgery for religion and art.

The act of castration was practiced from ancient times. In countries of Middle and Far East, castration was often done to provide eunuchs as guardians of the harems. In Europe and especially in Italy, it was carried out to preserve the male voice unbroken into adult life. From 16th century till the end of 18th century, castrati singers dominated opera with their supernatural voices. Boys were castrated mainly before the age of 9 years and when they grew up they had feminine characteristics, such as smooth, hairless bodies, breasts, infantile penis. The training procedure to become a castrato singer was very intense and lasted up to ten years. The most common surgical technique was either to sever the spermatic cords or crush the testis with the fingers. The voice of a castrato was the outcome of a larynx the size of a child's combined with the lung volume of an adult male. The castrati singers became superstars who dominated opera, singing both male and female roles for more than 200 years. Castrated for art, the beauty, range and flexibility of their voices raised them to mythical status.

Zinc α2-glycoprotein as a potential novel urine biomarker for the early diagnosis of prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? The use of biomarkers to detect a cancer early, especially prostate cancer, is not a new idea and PSA has been proved to be the best biomarker for the early diagnosis of prostate cancer. Since the introduction and wide use of PSA various efforts have been made to find novel biomarkers in both serum and urine of individuals at high risk for prostate cancer. The best example of a biomarker detected in the urine after a vigorous digital rectal examination is PCA3, which is used mainly in the subgroup of patients with PSA 4-10 ng/mL whose prostate biopsy was repeatedly negative for prostate cancer in order to decide the performance or not of a new biopsy. Proteomics is a state of the art new biotechnology used to identify the proteome of a certain tissue meaning the whole group of proteins related to the anatomy and biochemistry of the tissue. Using proteomics can effectively and more specifically identify proteins that can be used as potential biomarkers for the early diagnosis of prostate cancer. Zinc α2-glycoprotein has been studied in the past as a protein related to cancer cachexia and it has been measured in both prostate tissue and serum in patients with prostate cancer. Zinc α2-glycoprotein has also been recently identified by proteomics in prostate tissue showing different values in patients with prostate cancer and benign prostate hyperplasia. It is the first time that zinc α2-glycoprotein has been systematically measured and studied in an easily obtained biological fluid such as urine showing a very optimistic potential both as a novel solo biomarker and as an adjunct to PSA for the early diagnosis of prostate cancer. PSA has revolutionized the way we approximate prostate cancer diagnosis. Even though PSA is still the best biomarker for the diagnosis of prostate cancer it constitutes an organ-specific and not a disease-specific biomarker and diagnostic dilemmas are often raised concerning the performance or not of a prostate biopsy. Thus novel biomarkers are required in order to improve the diagnostic ability of PSA. Increasingly in the literature it is stated that the future of prostate cancer diagnosis could be not a single biomarker but a band of different biomarkers that as a total could give the possibility of an individual having prostate cancer. By detecting and measuring zinc α2-glycoprotein in the urine we believe that interesting conclusions can be made: first that proteomics is the way to detect with accuracy proteins that could be proved to be valuable novel biomarkers; second that zinc α2-glycoprotein detected in the urine could be used both as a solo biomarker and as an adjunct to PSA for the early diagnosis of prostate cancer. OBJECTIVE: • To examine the potential utility as a novel biomarker in the urine of zinc α2-glygoprotein (ZAG) for the early diagnosis of prostate cancer. PATIENTS AND METHODS: • The urine of 127 consecutive candidates for a transrectal ultrasound prostatic biopsy with a mean age of 65.7 ± 8.7 years and mean PSA 9.1 ± 5.3 ng/mL was collected. • Western blot analysis and immunohistochemistry for ZAG were performed. • Receiver operating characteristic curves and logistic regression models were used to estimate the predictive ability of ZAG and to determine the optimal sensitivity and specificity by using various cut-off values for the prediction of prostate cancer. RESULTS: • In all, 42 patients had prostate cancer, 29 showed high grade prostatic intraepithelial neoplasia and 56 were negative. • Receiver operating characteristic curve analysis showed a significant predictive ability of ZAG for prostate cancer. The area under the curve (AUC) for the prediction of prostate cancer was 0.68 (95% CI 0.59-0.78). • The combination of ZAG with PSA showed a significant improvement in the predictive ability (P= 0.010), with AUC equal to 0.75 (95% CI 0.66-0.85). Separate analysis in patients with PSA levels of 4-10 ng/mL (70.1%) showed that ZAG had a discriminative power with AUC equal to 0.68. • The optimal cut-off was 1.13 for ZAG, which corresponded to 6.88 times greater odds for prostate cancer. CONCLUSIONS: • Urine detected ZAG showed promising results in the prediction of prostate cancer. • Further validation is required to establish ZAG as a novel biomarker.

Implementation and external validation of Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score for predicting complications in 74 consecutive partial nephrectomies.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Partial nephrectomy (PN) is the gold standard operation for small renal tumours. The decision for or against a PN has been based mostly on preoperative radiological evaluation of the tumour. Three nephrometry scoring systems have been recently proposed for prediction of postoperative complications of PN (RENAL, C-index and PADUA). We validate externally the accuracy of the PADUA system and suggest for the first time a novel scoring system, based on the original PADUA system, which implements three other significant factors for the postoperative course of a partial. OBJECTIVE: • To externally validate the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours managed by partial nephrectomy (PN). PATIENTS AND METHODS: • Seventy-four consecutive patients in a single academic tertiary institution underwent open PN. • Incidence of 90-day complications was stratified by several clinicopathological variables, such as gender, age of the patient, hospital stay, pathology report, tumour characteristics and positive surgical margins. PADUA scores were given to each case. • The severity of complications was also categorized with the Clavien system. RESULTS: • The optimal threshold of PADUA for the prediction of complications was 8 with a sensitivity equal to 90.9% and a specificity equal to 77.8% (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.73-1.00). • Multivariate analysis revealed that that PADUA is an independent predictor for the risk of complications. • Also, PADUA score ≥ 8 identified a group of patients with almost 20-fold higher risk of complications (hazard ratio [HR]= 19.82; 95% CI, 1.79-28.35; P= 0.015). • Patients with papillary histology had greater risk for complications than those with clear-cell tumours (HR = 4.88; 95% CI, 1.34-17.76; P= 0.016). CONCLUSIONS: • The PADUA score is a simple anatomical system that predicts the risk of postoperative complications. This is the first external validation of this system for open PN from a single centre. • The authors believe that PADUA is an efficient tool, since the only variable of the present study that predicted a higher incidence of complications was the histology type, which is determined after surgery. • However, it should be applied to laparoscopic and robot-assisted series and it could also include the ischaemia time and surgeon experience in the overall scoring to be complete.

Time to castration resistance is an independent predictor of castration-resistant prostate cancer survival.

BACKGROUND/AIM: Easily assessable clinical predictors of response to chemotherapy in advanced castration-resistant prostate cancer (CRPC) are few. The objective of this retrospective study was to search for and identify such candidate predictors of outcome. PATIENTS AND METHODS: A retrospective analysis of clinical data of CRPC patients entered in the Clinical Therapeutics' departmental prostate cancer database from 1996-2009 was performed. Univariate and multivariate analyses for progression-free survival and overall survival included patients receiving both docetaxel- and non-docetaxel-containing regimens. RESULTS: From 1996 until June 2009, 286 out of 313 patients in our database were treated with chemotherapy. Prostate-specific antigen (PSA) reduction >30% correlated with improved survival irrespective of treatment. Beyond previously reported predictors, i.e. baseline PSA >30 ng/dl, hemoglobin below 10 mg/dl, weight loss, poor performance status, elevated lactic dehydrogenase and alkaline phosphatase, and time to CRPC of less than or equal to two years was associated with a poor overall survival and shorter progression-free survival upon univariate analysis. Pain was associated with shorter survival. Multivariate analysis confirmed time to CRPC, lactate dehydrogenase and alkaline phosphatase as independent predictors of overall and progression-free survival. CONCLUSION: Time to castration resistance is an important predictor of outcome in CRPC. PSA reduction >30% predicts survival improvement following chemotherapy for CRPC regardless of chemotherapy applied.

Intermittent docetaxel chemotherapy in patients with castrate-resistant prostate cancer.

OBJECTIVES: To determine whether intermittent docetaxel might control disease while limiting the toxicity and improving the quality-of-life parameters in patients with advanced, castrate-resistant prostate cancer. Intermittent docetaxel represents an appealing therapeutic approach. METHODS: We reviewed the records of 35 patients with chemotherapy-naive castrate-resistant prostate cancer who had received docetaxel 45 mg/m(2) every 2 weeks, with oral prednisone 5 mg twice daily. Treatment was held when the patients had reached a >50% prostate-specific antigen reduction from baseline that was confirmed by a second measurement 4 weeks later, in the absence of disease progression. Docetaxel was resumed at a >25% prostate-specific antigen increase from the nadir level, also confirmed by a second measurement 4 weeks later, or in cases of documented disease progression. RESULTS: Of the 35 patients, 18 (51.42%) had entered the first chemotherapy-free interval (CFI) after a median of 6 infusions (range 2-12), 6 patients had entered a second CFI after a median of 4 months (range 2-12), and 1 patient, a third CFI at the last follow-up point. The median interval "off chemotherapy" was 4.5 months (range 1-16) for the first CFI. Two patients discontinued docetaxel because of Grade 4 nonhematologic toxicity. The median interval to treatment failure was 8.1 months (95% confidence interval 5.1-12.2) for the entire cohort and 12.2 months (95% confidence interval 8.3-25+) for the patients who had entered the first CFI. CONCLUSIONS: The results of our study have shown that intermittent docetaxel is a clinically active and likely more tolerable and less costly therapeutic strategy for patients with castrate-resistant prostate cancer than continuous administration. Additional validation of this approach is warranted.

Prognostic and predictive factors in patients with androgen-independent prostate cancer treated with docetaxel and estramustine: a single institution experience.

OBJECTIVES: To investigate potential prognostic and predictive factors in patients with androgen-independent prostate cancer (AIPC) treated with docetaxel chemotherapy. METHODS: This analysis included 94 consecutive AIPC patients who were treated between March 2001 and May 2006 with biweekly docetaxel 45 mg/m(2) (day 2) and estramustine 140 mg three dimes daily (days 1-3). RESULTS: Prostate-specific antigen (PSA) responses were observed in 45 of 84 evaluable patients (53%), whereas objective responses were observed in 16 of 40 patients with measurable disease (40%). Median survival (OS) was 16.2 mo (95% confidence interval [CI], 12.9-19.4) and median time to PSA progression (TTP) 5.0 mo (95%CI, 3.6-7.1). OS was independently associated with pain score baseline PSA and weight loss. Patients with only extraosseous disease had higher PSA response rate (87% vs. 49%, p=0.014) and superior TTP compared with patients with bone metastases with or without extraosseous disease (7.3 vs. 4.3 vs. 4 mo, p=0.002). Concurrent bone and extraosseous metastases were associated with worse prognosis compared with each site alone (median OS: 12.3 vs.19 vs.18.3 mo, p=0.007). CONCLUSIONS: Among patients with AIPC treated with biweekly docetaxel and estramustine, baseline PSA >100, existence of pain, weight loss, and simultaneous extraosseous and bone disease were associated with worse prognosis. Extraosseous metastases seem to be more sensitive than bone disease to this chemotherapy.

Local anesthesia during transrectal ultrasonography-guided prostate biopsy: does it have any effect on sexual function?

INTRODUCTION: TRUS (Trans Rectal Ultra Sonographic)-guided biopsy of the prostate is the procedure of choice for prostate cancer diagnosis in urological clinical practice. TRUS-guided biopsies are associated with pain and anxiety and may interfere with sexual function and potency. The aim of this study was to evaluate whether local anesthesia during TRUS-guided prostate biopsies has any effect on the sexual behavior of patients and to compare the periprostatic infiltration with lidocaine to simple sonographic gel application in a randomized prospective trial. PATIENTS AND METHODS: A total of 62 consecutive patients were included in the study randomized in two groups; Group A (n = 30, control group) and Group B (n = 32, lidocaine infiltration group). Interviews regarding their sexual status were conducted at the time they were informed of the need for biopsy, at the time of biopsy and at two scheduled interviews following the biopsy. RESULTS: Similar results of sexual dysfunction were observed between the two groups. About 6% of patients experienced some degree of dysfunction in anticipation of biopsy (P > 0.02 between the two groups) that was resolved by the end of the follow-up period. In total, only one Group B patient continued to show sexual dysfunction at the time of the last interview compared to two patients in Group A. CONCLUSIONS: Local infiltration with lidocaine does not seem to play a role in sexual dysfunction following prostate biopsies. Psychological factors influence patients and the urologist should be ready to inform and reassure both the patient and his family.

Efficacy of tolterodine in preventing urge incontinence immediately after prostatectomy.

PURPOSE: Urgency and urge incontinence are frequently observed after prostatectomy. Although symptoms ameliorate within a relatively short time, they usually cause significant stress and anxiety to the patient as far as their duration is concerned. Aim of our study was to determine the efficacy of tolterodine in preventing urgency and urge incontinence after catheter removal in patients that underwent prostatectomy for benign prostate hyperplasia. PATIENTS AND METHODS: Twenty-seven patients with moderate/severe lower urinary tract symptoms due to benign prostatic enlargement, scheduled for prostatectomy, were randomised into two groups, Group A (14 pts) received tolterodine 2 mg b.i.d starting the day of surgery, while group B patients received no such treatment. Tolterodine treatment was discontinued 15 days after catheter removal. All patients completed the International Prostatic Symptom Score (IPSS) and the International Continence Society (ICS-BPH) forms the day before surgery, and three times more, one, fifteen and thirty days after catheter removal. RESULTS: Pre-operative total 1PSS and frequency of urgency/urge incontinence as determined by questions 3 and 4 of the ICS-BPH questionnaire were equally distributed between groups. Tolterodine was well tolerated and no adverse effects were reported. Post-operative IPSS and QoL scores did not differ between groups. However, the frequency of urge incontinence both the first day and fifteen days after catheter removal was significantly lower in the tolterodine group (16.6% vs. 69.2%, p=0.004 and 8.3% vs. 38.4%, p=0.039, respectively). CONCLUSION: Tolterodine was well tolerated in all patients and had a beneficial effect regarding the postoperative urge incontinence. Trials of a larger scale could determine which patients would benefit more, especially according to the presence of storage lower urinary tract symptoms prior to surgery.