Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy

Background

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.

Objective

This study evaluated the clinical utility of the PROGENSA PCA3 assay.

Design, setting, and participants

This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.

Measurements

After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).

Results and limitations

In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score ≥7 versus <7, and “significant” versus “indolent” (clinical stage T1c, PSA density [PSAD] <0.15 ng/ml, Gleason score in biopsy ≤6, and percent positive cores ≤33%) pCA.

Conclusions

The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.     

A switch from GnRH agonist to GnRH antagonist in castration-resistant prostate cancer patients leads to a low response rate on PSA

Purpose

At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months.

Methods

Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (<0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders.

Results

Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients.

Conclusion

Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.     

Sexual Rehabilitation and Penile Pain Associated with Intracavernous Alprostadil after Radical Prostatectomy

IntroductionIntracavernous alprostadil injection (IAI) is widely used for sexual rehabilitation (SR) after radical prostatectomy (RP). However, the rate of spontaneous erection recovery with IAI remains unclear, and IAI causes pain that may hinder SR.AimsTo assess SR in IAI users after RP and to evaluate the course and impact on SR of postinjection penile pain.MethodsWe prospectively studied 87 patients who underwent nerve‐sparing laparoscopic RP, reported normal preoperative erectile function, and used IAI for 12 months. Patients started with 2.5 µg alprostadil and were advised to increase the dose gradually until erection hardness allowed vaginal penetration.Main Outcome MeasuresAt 6 and 12 months, the International Index of Erectile Function (IIEF‐15) and Erection Hardness Score (EHS) were determined with and without IAI, and injection‐related penile pain was assessed using a numeric rating scale. Correlations linking penile pain, IIEF‐15, and EHS scores were evaluated.ResultsThe mean alprostadil dose was 8.1 µg after 6 months and 9.9 µg after 12 months. With/without IAI, mean IIEF‐15 scores for erectile and orgasmic function and mean EHS score were 14.6/4.6, 4.1/2.1, and 2.5/0.4, respectively, after 6 months; and 17.2/5.4, 4.9/2.6, and 2.7/0.9 after 12 months. Pain scores were 3.2 ± 2.5/10 and 2.5 ± 2.5/10 after 6 and 12 months, respectively. Pain intensity correlated with erectile function (r = ?0.23), intercourse satisfaction (r = ?0.23), and overall satisfaction (r = ?0.24) after 6 months but not after 12 months. Follow‐up was short and only patients who used IAI for 12 months were included.ConclusionsIn patients who were willing and able to use IAI, erectile function improved after 1 year but remained below preoperative levels. The adverse impact of pain on SR was significant during the first 6 months and diminished over time. These data may help to counsel IAI users with painful erections. Yiou R, Cunin P, de la Taille A, Salomon L, Binhas M, Lingombet O, Paul M, and Abbou C. Sexual rehabilitation and penile pain associated with intracavernous alprostadil after radical prostatectomy.     

Adenovirus types associated with severe respiratory diseases: A retrospective 4‐year study in Kuwait

Human adenovirus (HAdV) infection can result in a severe respiratory disease. The aim of this study was to identify HAdV types detected in patients hospitalized for severe respiratory illness. The study population consisted of 743 patients with severe respiratory disease admitted to four major hospitals in Kuwait between January 2013 and December 2016. Respiratory specimens were retrospectively screened for 20 respiratory viruses by real‐time PCR. The HAdV hexon gene was amplified and directly sequenced, and HAdV types were identified by performing Bayesian phylogenetic analysis. HAdV DNA was detected in 27 (3.6%) patients, with peaks in November and March. Most patients were infants and young children suffering from pneumonia or acute bronchiolitis. The detected HAdV types were C1, C2, C5, B3, and B7. Clusters of HAdV C1, C2, and C5 were observed with high posterior probability. All patients infected with HAdV C5 and 50% of patients infected with HAdV C2 or B7 were admitted to the intensive care unit (ICU). Co‐infection with other viruses was detected in 44.4% of patients. The most common co‐infecting virus was rhinovirus (HRV). HAdV/HRV co‐infection was detected in two children who presumably developed disseminated HAdV infection and died. This is the first report describing the circulation of HAdV types associated with severe outcomes in Kuwait. These findings highlight the need for a national surveillance system to monitor changes in predominant HAdV types and increased numbers of severe respiratory infections.

     

The importance of IL-6 protein expression in primary human renal cell carcinoma: an immunohistochemical study

AIMS: Interleukin 6 (IL-6) is produced by some renal carcinoma cell lines in vitro. This might be biologically important because IL-6 is a cytokine of particular interest, owing to its involvement in the growth of renal cell carcinoma. In this study, the expression of IL-6 protein in tissue samples from primary renal cell carcinoma was analysed, and then its clinical importance was examined. METHODS: The distribution of IL-6 in renal cell carcinoma was examined by means of an immunohistochemical method in 47 untreated primary renal cell carcinoma samples. The search for a significant difference between histological patterns, Furhman's grading system, TNM classification, and IL-6 protein expression was carried out. RESULTS: Immunohistochemistry demonstrated that IL-6 is expressed in 70% of primary tumours. There was no significant difference in the tumour size and grade between renal cell carcinomas with or without IL-6 expression. However, a relatively large number of high grade tumours expressed IL-6. CONCLUSION: The importance of IL-6 expression with regard to tumour size/local growth is questionable because IL-6 has been correlated with the development of metastatic disease. These data suggest that the production of IL-6 could exert a growth inhibitory effect on primary renal cell carcinoma.     

Prognostic value of EGF receptor and tumor cell proliferation in bladder cancer: therapeutic implications

Changes in growth factor receptor expression may confer a growth advantage on tumour cells. Epidermal growth factor-receptor (EGF-R) has been associated with the genesis of bladder tumours. We sought a link between EGF-R expression and MIB-1 cell proliferation and examined their prognostic value in the progression of bladder cancer. Fresh frozen samples from 113 transitional cell carcinomas (TCC) of the bladder and 10 healthy bladders were studied by immunohistochemistry, using monoclonal antibodies for EGF-R expression and MIB-1 for cell proliferation. Qualitative and quantitative immunostaining were analyzed in relation to time to progression and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). EGF-R stained more intensively in invasive tumours. Median nuclear over-expression of MIB-1 was 28%. Progression free survival rate estimates (log rank test) were significantly lower in patients EGF-R positive and with MIB-1 score above 28% (P < 0.0001, P < 0.0001, respectively). Multivariate analysis indicated that MIB-1 immunostaining was the most significant independent variable and EGF-R expression had no additional prognostic value over clinical stage and grade and cell proliferation. The MIB-1 proliferation index is a stronger predictor of bladder tumour progression than is EGF-R over-expression. This marker yield significant prognostic information in addition to stage and grade and may be of value for the clinical management of superficial and invasive bladder carcinomas. The pattern of EGF-R immunostaining and its association with tumour progression makes it a candidate for antigrowth factor therapy.     

Does the extraperitoneal laparoscopic approach improve the outcome of radical prostatectomy?

Laparoscopic radical prostatectomy (LRPE) became the operative procedure of choice for patients with clinically localized prostate cancer in selected urologic centers around the world. Principal advantages are the minimal invasive nature of the procedure, a superior visualization of the operative field because of the magnification of the optical system, an exact and watertight anastomosis, the possibility of early catheter removal, and a potentially reduced amount of blood loss. Recent data show that oncologic outcome is not compromised by the minimal invasive nature of the procedure. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal organ of the prostate. Therefore, principal disadvantages of LRPE are potential intraperitoneal complications. Endoscopic extraperitoneal radical prostatectomy is a further advancement of minimal invasive surgery because it overcomes the limitations of LRPE by the strictly extraperitoneal route of access, combining the advantages of minimal invasive surgery with the advantages of an extraperitoneal procedure. This article reviews the literature on minimally invasive (laparoscopic and endoscopic-extraperitoneal) radical prostatectomy.