Alexandre E. Pelzer

Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality

To evaluate the effectiveness of a well‐controlled programme of early detection and treatment of prostate cancer in the population of Tyrol, Austria, where such a programme of early detection and treatment was initiated in 1988 and where prostate‐specific antigen (PSA) testing was offered for free to all men aged 45–75 years from 1993.

Robotic Anderson-Hynes pyeloplasty: 5-year experience of one centre.

To present our 5‐year experience with robotically assisted laparoscopic pyeloplasty (RALP), as LP has been shown to have similar success rates as open surgery, but standard LP requires high operative skills and a correspondingly long period of training, limiting its widespread availability, and RALP is easier and quicker to learn due to facilitated intracorporeal suturing.

Ultrasound of prostate cancer: recent advances

Prostate cancer is the most common cancer in men. In the future, a significant further increase in the incidence of prostate cancer is expected. Therefore, improvement of prostate cancer diagnosis is a main topic of diagnostic imaging. The systematic prostate biopsy (“ten-core biopsy”) is now the “gold standard” of prostate cancer diagnosis but may miss prostate cancer. Contrast-enhanced colour Doppler ultrasound (US) and elastography are evolving methods that may dramatically change the role of US for prostate cancer diagnosis. Contrast-enhanced colour Doppler US allows for investigations of the prostate blood flow and consequently for prostate cancer visualization and therefore for targeted biopsies. Comparisons between systematic and contrast-enhanced targeted biopsies have shown that the targeted approach detects more cancers and cancers with higher Gleason scores with a reduced number of biopsy cores. Furthermore, elastography, a new US technique for the assessment of tissue elasticity has been demonstrated to be useful for the detection of prostate cancer, and may further improve prostate cancer staging. Therefore, contrast-enhanced colour Doppler US and elastography may have the potential to improve prostate cancer detection, grading and staging. However, further clinical trials will be needed to determine the promise of these new US advances.

Annexin A3 in Urine: A Highly Specific Noninvasive Marker for Prostate Cancer Early Detection

PURPOSE In prostate cancer cases the early diagnosis of tumors carrying a high risk of progression is of the utmost importance. There is an urgent clinical need to avoid unnecessary biopsies and subsequent overtreatment. We validated annexin A3 as a diagnostic marker for prostatic disease in typical clinical populations and relevant segments, such as patients with a negative digital rectal examination and low prostate specific antigen. MATERIALS AND METHODS We performed a blinded clinical study (ClinicalTrials.gov Identifier NCT00400894) from September 2005 to January 2007 in 591 patients who were continuously recruited from 4 European urological clinics. Urine was obtained directly after digital rectal examination and the annexin A3 concentration in urine was quantified by Western blot. Statistical analysis included combinations of annexin A3 with total, percent free, complexed and percent complexed prostate specific antigen. RESULTS Combined readouts of prostate specific antigen and urinary annexin A3 were superior to all others with an area under the ROC curve of 0.82 for a total prostate specific antigen range of 2 to 6 ng/ml, 0.83 for a total prostate specific antigen range of 4 to 10 ng/ml and 0.81 in all patients. The best performing prostate specific antigen derivative was percent free prostate specific antigen with an area under the ROC curve of 0.68 for a total prostate specific antigen range of 2 to 6 ng/ml, 0.72 for a total prostate specific antigen range of 4 to 10 ng/ml and 0.73 in all patients. Annexin A3 has an inverse relationship to cancer and, therefore, its specificity was much better than that of prostate specific antigen. CONCLUSIONS Annexin A3 quantification in urine provides a novel noninvasive biomarker with high specificity. Annexin A3 is complementary to prostate specific antigen or to any other cancer marker. It has a huge potential to avoid unnecessary biopsies with a particular strength in the clinically relevant large group of patients who have a negative digital rectal examination and prostate specific antigen in the lower range of values (2 to 10 ng/ml).

Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction.

Associate Editor

Development of a Multiplexed Urine Assay for Prostate Cancer Diagnosis

BACKGROUND Several studies have demonstrated the value of DNA methylation in urine-based assays for prostate cancer diagnosis. However, a multicenter validation with a clinical prototype has not been published. METHODS We developed a multiplexed, quantitative methylation-specific polymerase chain reaction (MSP) assay consisting of 3 methylation markers, GSTP1, RARB, and APC, and an endogenous control, ACTB, in a closed-tube, homogeneous assay format. We tested this format with urine samples collected after digital rectal examination from 234 patients with prostate-specific antigen (PSA) concentrations > or =2.5 microg/L in 2 independent patient cohorts from 9 clinical sites. RESULTS In the first cohort of 121 patients, we demonstrated 55% sensitivity and 80% specificity, with area under the curve (AUC) 0.69. In the second independent cohort of 113 patients, we found a comparable sensitivity of 53% and specificity of 76% (AUC 0.65). In the first cohort, as well as in a combined cohort, the MSP assay in conjunction with total PSA, digital rectal examination status, and age improved the AUC without MSP, although the difference was not statistically significant. Importantly, the GSTP1 cycle threshold value demonstrated a good correlation (R = 0.84) with the number of cores found to contain prostate cancer or premalignant lesions on biopsy. Moreover, samples that exhibited methylation for either GSTP1 or RARB typically contained higher tumor volumes at prostatectomy than those samples that did not exhibit methylation. CONCLUSIONS These data confirm and extend previously reported studies and demonstrate the performance of a clinical prototype assay that should aid urologists in identifying men who should undergo biopsy.

Factors contributing to the racial differences in prostate cancer mortality.

To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African‐Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups.

Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease?

There is a wide variety of topics in this section of the Journal this month. The papers come from Austria, Israel, Scotland, Denmark, England and Australia. I am, as ever, pleased that the Journal continues to receive papers from so many countries, and that the high standard of these papers help us to maintain a quality product of great general interest to the reader.

The Expression of Transcription Factor Activating Transcription Factor 3 in the Human Prostate and its Regulation by Androgen in Prostate Cancer

PURPOSE ATF3 is a member of the basic leucine zipper/cyclic adenosine monophosphate responsive element binding protein family of transcription factors. There is overwhelming evidence that it is a stress inducible factor acting in a signal-type and cell-type dependent manner, and it is involved in cell proliferation and survival. We found that ATF3 was differently expressed in an in vitro prostate cancer tumor progression model and we investigated the possible role of ATF3 in prostate cancer. MATERIALS AND METHODS ATF3 up-regulation in vivo/in vitro and androgen regulation were assessed by immunohistochemistry and immunoblot analysis. Results after forced ATF3 transfection were evaluated by proliferation assay and cell cycle analysis. RESULTS Immunohistochemistry and immunoblot analysis revealed ATF3 up-regulation in prostate cancer in vitro and in vivo, and stimulation of expression by androgens. Antiandrogen treatment decreased ATF3 expression in androgen sensitive cells but acted as a stimulator in long-term androgen ablated cells representing a model for therapy refractory disease. Expression in tumors increased with higher Gleason scores and highest expression was observed in samples of therapy refractory tumor tissue. Forced ATF3 over expression in a prostate cancer cell line induced cell proliferation and accelerated cell cycle progression from G1 to S-phase. CONCLUSIONS These data provide new insight into the role of ATF3 in prostate cancer development and/or progression. They indicate that ATF3 is an androgen regulated gene that is highly expressed in prostate tumors and stimulating cell proliferation. It represents a possible target for prostate cancer therapy.

Tumor Recurrence in the Remnant Urothelium of Females Undergoing Radical Cystectomy for Transitional Cell Carcinoma of the Bladder: Long-Term Results From a Single Center

PURPOSE We analyzed the risk factors and incidence of secondary TCC of the remnant urothelium in women following radical cystectomy for TCC of the bladder. MATERIALS AND METHODS A total of 85 women with a mean age of 64.5 years with clinically localized TCC of the bladder underwent radical cystectomy between 1992 and 2004. Orthotopic bladder substitution was performed in 46 females, while 39 underwent nonorthotopic urinary diversion. Of the entire cohort 22 (26%) patients underwent cystectomy for multifocal or recurrent TCC. Followup examinations were performed at 6-month intervals. RESULTS Mean followup in the entire cohort was 49.8 months (median 42). Intraoperative frozen sections obtained from the urethra and distal ureters were negative for TCC and CIS in all patients. Four women (4.7%) had TCC in the remnant urothelium at a mean of 56 months postoperatively. These patients had undergone cystectomy for multifocal or recurrent TCC (4 of 22 or 18%). No secondary TCC was seen in the 63 patients with solitary invasive or nonrecurrent bladder cancer (p <0.05). Urethral recurrence was found in 2 patients (4.3%) 65 and 36 months after orthotopic neobladder surgery, respectively. In the orthotopic group 1 patient (2.1%) had an upper urinary tract tumor 76 months after surgery, while in the nonorthotopic group 1 (2.5%) was found to have an upper urinary tract tumor 48 months postoperatively. CONCLUSIONS Recurrent or multifocal TCC may represent a risk factor for secondary TCC of the remnant urothelium after cystectomy. In our series all recurrent tumors were late recurrences (more than 36 months postoperatively). Because the rate of urethral recurrence in the current series corresponds to that reported in men (2% to 6%), urethra sparing cystectomy with orthotopic bladder replacement does not appear to compromise the oncological outcome in women.