Silvan Boxler

Matrix Metalloproteinases and Angiogenic Factors: Predictors of Survival after Radical Prostatectomy for Clinically Organ-Confined Prostate Cancer?

The aim of the present study was to investigate whether biomarkers improve the prediction of recurrence-free, disease-specific, and overall survival in patients with clinically localized prostate cancer. A tissue microarray was constructed from prostate specimens of 278 patients who underwent open radical retropubic prostatectomy for clinically localized prostate cancer. For immunohistochemical studies, antibodies were used against matrix metalloproteinase (MMP)-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19, as well as against vascular endothelial growth factor, hypoxia-induced factor 1α, basic fibroblast growth factor, and cluster of differentiation 31. Univariate and multivariable analyses were performed to evaluate the potential predictors of overall, disease-specific, and recurrence-free survival. In univariate analysis of patients with clinically organ-confined prostate cancer, only higher expression levels of MMP-9 (hazard ratio [0.6], 95% CI 0.45-0.8) had a protective effect in terms of overall survival. This positive effect of high MMP-9 expression was also observed for recurrence-free (HR 0.88, 95% CI 0.78-0.99) and disease-specific survival (HR 0.5, 95% CI 0.36-0.73). In multivariable analysis, none of these potential markers was found to be an independent prognostic factor of survival. Of all MMPs and angiogenic factors tested, MMP-9 expression has the potential as a prognostic marker in patients undergoing radical prostatectomy for clinically organ-confined cases of prostate cancer.

Patients with an Orthotopic Low Pressure Bladder Substitute Enjoy Long-Term Good Function

PURPOSE Orthotopic bladder substitution has been performed on a regular basis for more than 30 years and yet data on long-term functional outcomes are still lacking. MATERIALS AND METHODS We evaluated 181 men and 19 women who underwent radical cystectomy and urinary diversion with ileal orthotopic bladder substitution from 1985 to 2004 and who had 10 years or more of followup. RESULTS Median age at radical cystectomy was 63 years (IQR 57-69). Median followup was 167 months (IQR 137-206). Daytime and nighttime continence rates peaked 24 months postoperatively and decreased slightly thereafter during almost 2 decades. At 10, 15 and 20 years daytime continence rates were 92%, 90% and 79%, and nighttime continence rates were 70%, 65% and 55%, respectively. During the day and at night fewer than 3% and 10% of patients, respectively, had urine loss 100 ml or greater at any time 10 years or longer after surgery. At 10 and 20 years 11 of 200 patients (6%) and 1 of 29 (3%), respectively, had to perform clean intermittent self-catheterization. After an initial postoperative decrease in the estimated glomerular filtration rate the subsequent decrease was less than 1 ml/minute/1.73 m(2) per year. A total of 81 complications were observed in 42 of the 200 patients (21%) 10 years or longer after radical cystectomy with pyelonephritis as the most frequent cause. CONCLUSIONS Patients who survive up to 20 years after radical cystectomy and diversion with an ileal orthotopic bladder substitution may enjoy satisfactory urinary continence and retain the ability to void spontaneously while experiencing no more than a physiological decrease in renal function.

What is the Need for Prostatic Biomarkers in Prostate Cancer Management

Discriminating patients with a low risk of progression from those with lethal prostate cancer is one of the main challenges in prostate cancer management. Indeed, such discrimination is essential if we aim to avoid overtreatment in men with indolent disease and to improve survival in those men with lethal disease. We are reporting on the current literature on such prognostic tools that are now available, their clinical role and their limitations in individualizing care. There is an urgent need to incorporate such genomic tools into new platform-based clinical trial structures to further develop and validate prognostic and predictive biomarkers and provide prostate cancer patients with an effective and cost-efficient access to new drugs in the setting of personalized treatment.

Outcome predictors of radical cystectomy in patients with cT4 prostate cancer: A multi-institutional study of 62 patients

To identify which patients with macroscopic bladder‐infiltrating T4 prostate cancer (PCa) might have favourable outcomes when treated with radical cystectomy (RC).

Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid- to long-term continence

A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long‐term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy.

MP30-10 HIFU DOSE ESCALATION LEADS TO FEWER RECURRENCES IN FOLLOWING FOCAL HIFU IN PROSTATE CANCER

CONCLUSION HIFU dose escalation leads to fewer recurrences in following focal HIFU in prostate cancer P. M. Huber 1,4,6, N. Afzal 8, M. Arya 4,6,7, S. Boxler 1, S. Charman 3, A. Cornaby 3, T. Dudderidge 9, M. Emberton 3,4, S. Guillaumier 3,4, R. J. Hindley 10, L. Leemann 2, H. Lewi 11, N. McCartan 3,4, C. M. Moore 3,4, R. Nigam 12, C. Ogden 13, R. Persad 14, K. Shah 3, G. N. Thalmann 1, J. Virdi 7, M. Winkler 6, H. U. Ahmed 3,5,6 1. Department of Urology, University Hospital Inselspital Berne, CH; 2. Department of Political Science, University of Zurich, CH; 3. Division of Surgery and Interventional Sciences, University College London, London, UK; 4. Department of Urology, UCLH NHS Foundation Trust, London, UK; 5. Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; 6. Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK; 7. Department of Urology, The Princess Alexandra Hospital NHS Trust, Harlow, UK; 8. Department of Urology, Dorset County Hospital NHS Trust, Dorset, UK; 9. Department of Urology, University Hospital Southampton NHS Trust, Southampton, UK; 10. Department of Urology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, UK; 11. Springfield Hospital, Chelmsford, Essex, UK; 12. Department of Urology, Royal County Surrey Hospital NHS Trust, Surrey, UK; 13. Department of Academic Urology, The Royal Marsden Hospital NHS Foundation Trust, London, UK; 14. Department of Urology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK

PD15-12 THE IMPACT OF NERVE SPARING RADICAL PROSTATECTOMY ON ONCOLOGICAL AND FUNCTIONAL OUTCOMES IN PATIENTS WITH HIGH RISK PROSTATE CANCER: A RETROSPECTIVE LONG-TERM SINGLE CENTER STUDY

INTRODUCTION AND OBJECTIVES: Salvage radiation therapy (SRT) is a therapeutic option for men with PSA rising after radical prostatectomy (RP). While several studies have addressed potential predictors of outcome after SRT, none have investigated the role of the extent of pelvic lymph node dissection (PLND) on SRT outcomes. We hypothesised that cancer control of SRT are improved in men who underwent more extensive PLND at the time of RP. METHODS: The study included 728 patients who received SRT for either PSA rising after RP or PSA persistence after surgery that was defined as PSA level 0.1 ng/ml 1 month after RP. All patients received local radiation to the prostate and seminal vesicle bed at one of six tertiary referral centres; irradiation of the pelvic lymph node region (whole pelvic RT) was left to the discretion of the treating physician. The study outcome consisted of clinical recurrence after SRT as identified by radiologic imaging. Clinical recurrence included pelvic nodal, retroperitoneal nodal, skeletal, and visceral metastasis. Multivariable analysis tested the association between clinical recurrence and the number of lymph nodes removed, which was considered as a continuous variable. Covariates consisted of: pT stage ( pT3a vs. pT3b), pathologic Gleason score ( 7 vs. 8), surgical margin (negative vs. positive), PSA level at SRT, and radiation field (prostatic bed vs. whole pelvis). RESULTS: Median patient age was 66 years, while the median number of nodes removed at RP was 7 (IQR 0, 13). Overall, 500 (69%) patients received SRT for PSA rising after RP and 228 (31%) were irradiated for PSA persistence. Median PSA at SRT was 0.30 ng/ml. Whole pelvic SRT was delivered to 187 (27%) patients. Median follow-up was 94 months (IQR 48, 128), during which time. 27 (3.7%), 13 (2.1%), 61 (7.7%), and 11 (1.3%) patients developed pelvic, retroperitoneal, skeletal, and visceral metastasis, respectively. On multivariable analysis, the number of lymph nodes removed at RP was significantly inversely associated with the risk of clinical recurrence following SRT (hazard ratio: 0.97; 95% CI 0.95, 0.99; p1⁄40.039). CONCLUSIONS: This is the first study demonstrating a significant inverse correlation between the number of lymph nodes removed and the risk of clinical recurrence after SRT. These data suggest the need for consideration of alternative approaches to management for patients with PSA elevation after RP in whom a lower number of nodes were removed at surgery, including multimodal salvage therapy.

Urinary diversion in elderly patients

BACKGROUND Bladder cancer represents one of the ten most prevalent cancers worldwide. More than 400,000 people worldwide are newly diagnosed every year. Within 2 years after diagnosis, 80% of patients with muscle invasive bladder cancer without treatment die. METHODS The aggressive local surgical approach with a cystectomy is the therapy of choice. The median age of patients with de novo bladder cancer is 70 years. Thus bladder cancer is a cancer of the elderly. For demographical reasons, the number of eldery patients undergoing radical cystectomy will rise in the next few years. The type of urinary diversion is a major factor influencing perioperative morbidity and quality of life in these patients. Incontinent urinary diversions are preferentially used in daily practice. CONCLUSIONS There are only a few contraindications for orthotopic neobladder; however, age alone is not a contraindication. Patient selection and a nerve sparing approach are crucial in men and women to achieve excellent functional results with orthotopic neobladder in elderly patients.