Nicolaas Lumen

Etiology of Urethral Stricture Disease in the 21st Century

PURPOSE We determined the current etiology of urethral stricture disease in the developed world and whether there are any differences in etiology by patient age and stricture site. MATERIAL AND METHODS Between January 2001 and August 2007 we prospectively collected a database on 268 male patients with urethral stricture disease who underwent urethroplasty at a referral center. The database was analyzed for possible cause of stricture and for previous interventions. Subanalysis was done for stricture etiology by patient age and stricture site. RESULTS The most important causes were idiopathy, transurethral resection, urethral catheterization, pelvic fracture and hypospadias surgery. Overall iatrogenic causes (transurethral resection, urethral catheterization, cystoscopy, prostatectomy, brachytherapy and hypospadias surgery) were the etiology in 45.5% of stricture cases. In patients younger than 45 years the main causes were idiopathy, hypospadias surgery and pelvic fracture. In patients older than 45 years the main causes were transurethral resection and idiopathy. In cases of penile urethra hypospadias surgery idiopathic stricture, urethral catheterization and lichen sclerosus were the main causes, while in the bulbar urethra idiopathic strictures were most prevalent, followed by strictures due to transurethral resection. The main cause of multifocal/panurethral anterior stricture disease was urethral catheterization, while pelvic fracture was the main cause of posterior urethral strictures. CONCLUSIONS Of strictures treated with urethroplasty today iatrogenic causes account for about half of the urethral stricture cases in the developed world. In about 1 of 3 cases no obvious cause could be identified. The etiology is significantly different in younger vs older patients and among stricture sites.

Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

PURPOSE To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. METHODS AND MATERIALS Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. RESULTS The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. CONCLUSION The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

Salvage Stereotactic Body Radiotherapy for Patients With Limited Prostate Cancer Metastases: Deferring Androgen Deprivation Therapy

BACKGROUND We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases. PATIENTS AND METHODS Patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. RESULTS We treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed. CONCLUSION Repeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.

Salvage intensity-modulated radiotherapy for rising PSA after radical prostatectomy

INTRODUCTION The aim was to prospectively evaluate both acute and late toxicity and biochemical non-evidence of disease (bNED) in patients treated with salvage intensity-modulated radiotherapy (IMRT) +/- androgen deprivation (AD) for biochemical relapse after radical prostatectomy (RP). MATERIALS AND METHODS IMRT was prescribed to a mean prescription dose to the planning target volume (PTV) of 75 Gy to be delivered in 37 fractions of 2 Gy. In total, 135 patients were treated with IMRT. Median age was 64 years. Median PSA level was 0.8 ng/ml. AD was initiated in 94 patients. Indications were perineural invasion, seminal vesicle invasion or Gleason score > or = 8 at RP. (1) Acute toxicity (n = 135). All patients were available for this analysis. Acute toxicity was scored using an in-house developed scoring system. (2) Late toxicity (n = 68). Only patients with a follow-up of at least 18 months were considered for late toxicity analysis. The RILIT score was used to register gastro-intestinal (GI) toxicity. An in-house developed scale was used to register genito-urinary (GU) toxicity. (3) bNED (n = 87). For bNED, all AD-naive patients (n = 38) together with the AD-positive patients with a follow-up > or = 18 months (n = 49) were considered. Factors influencing the results of salvage treatment were analyzed. RESULTS (1) Acute toxicity (n = 135). No patient developed grade 3 GI toxicity. We observed grade 2 toxicity in 20 patients. Four patients developed grade 3 GU toxicity. (2) Late toxicity (n = 68). One patient developed grade 3 rectal blood loss. One patient developed grade 3 anal pain (anal fissure). We observed grade 2 GI toxicity in 9 patients. Two patients developed grade 3GU toxicity. Twenty-one patients developed grade 2 GU toxicity. We observed an urethral stricture in 5 patients. (3) bNED (n = 87). The 3- and 5-year bNED was 67%. Gleason score at RP, perineural invasion and capsular perforation were significant predictors for bNED. PSA before IMRT (<1.0 vs. 1.0 ng/ml) showed a trend in predicting bNED (p = 0.08). CONCLUSION IMRT to 75Gy+/-AD can be delivered with low levels of acute and late toxicity. In patients without perineural invasion and capsular invasion and with a Gleason score > or = 7 (3 + 4), IMRT offers very good 5-years bNED.

Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer.

In non‐castrate prostate cancer (PCa), the prognostic value of the number of metastases on prostate cancer‐specific survival (PCSS) is not well studied.

Adjuvant High-Dose Intensity-Modulated Radiotherapy after Radical Prostatectomy for Prostate Cancer: Clinical Results in 104 Patients

BACKGROUND Approximately 25% of patients treated with adjuvant radiotherapy (RT) will develop a biochemical failure within 5 yr after RT when doses of 60-64 Gray (Gy) are used. OBJECTIVE To report on the safety and biochemical outcome of adjuvant intensity-modulated RT (IMRT) with doses >70 Gy. DESIGN, SETTING, AND PARTICIPANTS Between 1999 and 2008, 104 patients underwent radical prostatectomy (RP) followed by adjuvant IMRT with or without androgen deprivation (AD) with a median follow-up of 36 mo. Indications for adjuvant IMRT were capsule perforation, seminal vesicle invasion (SVI) and/or positive surgical margins at prostatectomy specimen. All patients were irradiated at a single tertiary academic centre. AD was initiated on the basis of SVI, a preprostatectomy prostate-specific antigen level >20 ng/ml, Gleason score > or = 4+3 (n=36), or personal preference of the referring urologist (n=32). INTERVENTION A median dose of 74 Gy was prescribed to the planning target volume using IMRT in all patients. AD consisted out of a luteinising hormone-releasing hormone analogue for 6 mo. MEASUREMENTS We report on acute and late toxicity, biochemical relapse-free survival (bRFS), and clinical progression. The Kaplan-Meier method was used to estimate bRFS. Univariate analysis was used to examine the influence of patient- and treatment-related factors on bRFS. RESULTS AND LIMITATIONS With respect to acute toxicity, no patients developed grade 3 gastrointestinal (GI) toxicity, and eight patients developed grade 3 genitourinary (GU) toxicity (8%). With respect to late toxicity, no patients developed grade 3 GI toxicity, and four patients (4%) developed grade 3 GU toxicity. A urethral stricture was observed in six patients (6%). The 3- and 5-yr actuarial bRFS was 93%. On univariate analysis, bRFS rates were worse when SVI (p<0.02), Gleason score > or = 4+3 (p<0.02), or negative surgical margins (p<0.02) were present. AD did not influence bRFS. Six patients had a clinical relapse. CONCLUSIONS Adjuvant high-dose IMRT after prostatectomy is safe and bRFS is excellent.

EAU Guidelines on Iatrogenic Trauma

CONTEXT The European Association of Urology (EAU) Trauma Guidelines Panel presents an updated iatrogenic trauma section of their guidelines. Iatrogenic injuries are known complications of surgery to the urinary tract. Timely and adequate intervention is key to their management. OBJECTIVE To assess the optimal evaluation and management of iatrogenic injuries and present an update of the iatrogenic section of the EAU Trauma Guidelines. EVIDENCE ACQUISITION A systematic search of the literature was conducted, consulting Medline and the Cochrane Register of Systematic reviews. No time limitations were applied, although the focus was on more recent publications. EVIDENCE SYNTHESIS The expert panel developed statements and recommendations. Statements were rated according to their level of evidence, and recommendations received a grade following a rating system modified from the Oxford Centre for Evidence-based Medicine. Currently, only limited high-powered studies are available addressing iatrogenic injuries. Because the reporting of complications or sequelae of interventions is now increasingly becoming a standard requirement, this situation will likely change in the future. CONCLUSIONS This section of the trauma guidelines presents an updated overview of the treatment of iatrogenic trauma that will be incorporated in the trauma guidelines available at the EAU Web site (http://www. uroweb.org/guidelines/online-guidelines/).

High-Dose Salvage Intensity-Modulated Radiotherapy With or Without Androgen Deprivation After Radical Prostatectomy for Rising or Persisting Prostate-Specific Antigen: 5-Year Results

BACKGROUND Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70 Gy might result in improved outcome. OBJECTIVE To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD). DESIGN, SETTING, AND PARTICIPANTS Between 1999 and 2008, 136 patients were referred for HD-SIMRT with or without AD. The median follow-up was 5 yr. Indications for HD-SIMRT were persisting prostate-specific antigen (PSA) or a rising PSA following RP. All patients were irradiated at a single, tertiary, academic centre. AD was initiated on the basis of seminal vesicle invasion, preprostatectomy PSA >20 ng/ml, Gleason score ≥ 4+3 (n=43), or personal preference of the referring urologist (n=54). INTERVENTION A median 76-Gy dose was prescribed to the RP bed using intensity-modulated radiotherapy (IMRT) in all patients. AD consisted of a luteinising hormone-releasing hormone analogue for 6 mo. MEASUREMENTS Univariate and multivariate analyses were used to examine the influence of patient- and treatment-related factors on late toxicity, biochemical relapse-free survival (bRFS), and clinical relapse-free survival (cRFS). RESULTS AND LIMITATIONS The 5-yr actuarial bRFS and cRFS were 56% and 86%, respectively. On multivariate analysis, the presence of perineural invasion at RP (hazard ratio [HR]: 6.19, p=0.001) and an increasing pre-SRT PSA (PSA 0.5 ng/ml: HR: 1; PSA 1-1.5 ng/ml: HR: 1.60, p=0.30; and PSA >1 ng/ml: HR: 2.70, p=0.02) were independent factors for a decreased bRFS. The addition of AD improved bRFS (HR: 0.33, p=0.005). On multivariate analysis, none of the variables was a predictor of cRFS. The 5-yr risk of grade 2-3 toxicity was 22% and 8% for genitourinary and gastrointestinal symptoms, respectively. CONCLUSIONS IMRT allows for safe dose escalation to 76Gy with good bRFS.

Erectile Implants in Female-to-Male Transsexuals: Our Experience in 129 Patients

BACKGROUND The combination of a neourethra and erection prosthesis in a single neophallus in the female-to-male transsexual remains a challenge. No good data are available on this subject. OBJECTIVE To report the outcome in 129 female-to-male transsexuals with a neophallus after the implantation of an erectile prosthesis. DESIGN, SETTING, AND PARTICIPANTS From March 1996 until October 2007, 129 female-to-male transsexuals with a neophallus underwent the implantation of an erectile prosthesis. The mean follow-up was 30.2 mo (range: 0-132 mo). INTERVENTION A Dynaflex prosthesis was implanted initially in 9 patients, a three-piece hydraulic device (AMS CX or AMS CXM) in 50 patients, and a CX Inhibizone, Ambicor, and Coloplast/Mentor prosthesis in 17, 47, and 6 patients, respectively. MEASUREMENTS Data on outcome in these patients were retrospectively evaluated. RESULTS AND LIMITATIONS Of 129 patients, 76 patients (58.9%) still have their original implant in place. Fifty-three patients (41.1%) needed to undergo either removal or revision of the prosthesis due to infection, erosion, dysfunction, or leak. Forty-one patients underwent a replacement of the prosthesis, nine needed a second revision, five needed a third revision, and one patient needed a fourth revision of prosthesis. Malposition of prosthesis was corrected by surgical repositioning so that removal or revision could be avoided. Of 185 prostheses used in 129 patients, 108 (58.4%) still remain in place, with a total infection rate of 11.9%, a total protrusion rate of 8.1%, a total prosthesis leak rate of 9.2%, a total dysfunction rate of 13%, and a total malposition rate of 14.6%. The period of follow-up in the more recent types of prostheses (Ambicor, Coloplast/Mentor) is much shorter; therefore, comparison with earlier types is difficult to make. CONCLUSIONS Despite high complication rates, implantation of a hydraulic erectile prosthesis remains the best option for achieving the possibility of sexual intercourse in female-to-male transsexuals.

Urinary toxicity after high dose intensity modulated radiotherapy as primary therapy for prostate cancer

BACKGROUND AND PURPOSE Urinary toxicity plays a major role in the quality of life (QOL) of patients treated with external beam radiotherapy as primary therapy for prostate cancer. In this study we report on: (1) Incidence of acute and late GU toxicity after intensity modulated radiotherapy (IMRT) for prostate cancer at Ghent University Hospital (GUH). (2) Time evolution of pre-IMRT and IMRT-induced acute and late GU toxicity. MATERIALS AND METHODS At GUH, 260 patients with a follow-up of > or = 12 months were treated with IMRT for prostate cancer. The incidence and evolution of GU toxicity were recorded. RESULTS Acute grades 3, 2 and 1 GU toxicity occurred in 8%, 42% and 42% of the patients, respectively. Late grades 3, 2 and 1 GU toxicity occurred in 3%, 19% and 40% of the patients, respectively. During therapy baseline grade 1 symptoms increased into grade 2 acute GU toxicity in 48%. After 1 and 2 years, 60% and 70% of the patients, respectively, had less GU symptoms when compared to the pre-treatment status. CONCLUSION IMRT induces mild GU toxicity. There is an improvement in pre-IMRT obstructive miction disorders.