Roland van Velthoven

Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)

BACKGROUND Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. METHODS After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. FINDINGS The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). INTERPRETATION Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.

The Learning Curve for Laparoscopic Radical Prostatectomy: An International Multicenter Study

PURPOSE It is not yet possible to estimate the number of cases required for a beginner to become expert in laparoscopic radical prostatectomy. We estimated the learning curve of laparoscopic radical prostatectomy for positive surgical margins compared to a published learning curve for open radical prostatectomy. MATERIALS AND METHODS We reviewed records from 8,544 consecutive patients with prostate cancer treated laparoscopically by 51 surgeons at 14 academic institutions in Europe and the United States. The probability of a positive surgical margin was calculated as a function of surgeon experience with adjustment for pathological stage, Gleason score and prostate specific antigen. A second model incorporated prior experience with open radical prostatectomy and surgeon generation. RESULTS Positive surgical margins occurred in 1,862 patients (22%). There was an apparent improvement in surgical margin rates up to a plateau at 200 to 250 surgeries. Changes in margin rates once this plateau was reached were relatively minimal relative to the CIs. The absolute risk difference for 10 vs 250 prior surgeries was 4.8% (95% CI 1.5, 8.5). Neither surgeon generation nor prior open radical prostatectomy experience was statistically significant when added to the model. The rate of decrease in positive surgical margins was more rapid in the open vs laparoscopic learning curve. CONCLUSIONS The learning curve for surgical margins after laparoscopic radical prostatectomy plateaus at approximately 200 to 250 cases. Prior open experience and surgeon generation do not improve the margin rate, suggesting that the rate is primarily a function of specifically laparoscopic training and experience.

Cadaveric versus Porcine Models in Urological Laparoscopic Training

Introduction: Laparoscopy performed on anesthetized pigs is an established training model. In this pilot study, we performed laparoscopy on cadavers as a training modality for urologists participating in a laparoscopic seminar. Materials and Methods: We compared data from two consecutive laparoscopy seminars performed at our institution. The first included a laparoscopy session performed on pigs. The second was in the same setup, yet laparoscopy was performed on fresh cadavers. We analyzed and compared the trainees’ perspectives regarding the 2 modalities using a 5-scale satisfaction questionnaire. Results: Seven trainees attended the cadaveric and 9 the porcine laparoscopy session. The two groups were similar in terms of age and previous laparoscopic and urological experience. The general satisfaction of the two training modalities was high in the two groups, as well as their will for another session of the same kind. Yet the trainees ranked their understanding of the surgical anatomy, laparoscopic technique and use of instruments significantly higher in the cadaveric laparoscopy group (p values were 0.007, 0.006 and 0.032, respectively). Conclusions: Cadaveric laparoscopy may offer an ideal surgical environment allowing dissection and performance of complete procedures. In this pilot study, we conducted the first reported cadaveric laparoscopy training seminar in urology. The trainees preferred the cadaveric laparoscopy and found it superior to porcine laparoscopy. We believe that cadaveric laparoscopy is an important training tool, which may be added to the armamentarium of urological laparoscopy training courses.

Clinical and Cost Effectiveness of Hexaminolevulinate-guided Blue-light Cystoscopy: Evidence Review and Updated Expert Recommendations

CONTEXT Non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates. OBJECTIVE To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input. EVIDENCE ACQUISITION PubMed and conference searches, supplemented by personal experience. EVIDENCE SYNTHESIS Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time. CONCLUSIONS HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system. PATIENT SUMMARY Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours.

Clinical impact of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach

To assess the impact of a novel molecular imaging technique, 68Ga‐(HBED‐CC)‐prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate‐specific antigen (PSA) after treatment with curative intent.

Long-term analysis of oncological outcomes after laparoscopic radical cystectomy in Europe: results from a multicentre study by the European Association of Urology (EAU) section of Uro-technology.

To report long‐term outcomes of laparoscopic radical cystectomy (LRC) in a multicentre European cohort, and explore feasibility and safety of LRC.

MRI-Targeted Biopsies versus Systematic Transrectal Ultrasound Guided Biopsies for the Diagnosis of Localized Prostate Cancer in Biopsy Naïve Men

Introduction. To compare, in the same cohort of men, the detection of clinically significant disease in standard (STD) cores versus multiparametric magnetic resonance imaging (mpMRI) targeted (TAR) cores. Material and Methods. A prospective study was conducted on 129 biopsy naïve men with clinical suspicion of prostate cancer. These patients underwent prebiopsy mpMRI with STD systematic biopsies and TAR biopsies when lesions were found. The agreement between the TAR and the STD protocols was measured using Cohens kappa coefficient. Results. Cancer detection rate of MRI-targeted biopsy was 62.7%. TAR protocol demonstrated higher detection rate of clinically significant disease compared to STD protocol. The proportion of cores positive for clinically significant cancer in TAR cores was 28.9% versus 9.8% for STD cores (P < 0.001). The proportion of men with clinically significant cancer and the proportion of men with Gleason score 7 were higher with the TAR protocol than with the STD protocol (P = 0.003; P = 0.0008, resp.). Conclusion. mpMRI improved clinically significant prostate cancer detection rate compared to STD protocol alone with less tissue sampling and higher Gleason score. Further development in imaging as well as multicentre studies using the START recommendation is needed to elucidate the role of mpMRI targeted biopsy in the management of prostate cancer.

Current management of erectile dysfunction after cancer treatment

Purpose of review Erectile dysfunction has a major impact on quality of life. Treating sexual dysfunction after cancer treatment requires special concern because of specific medical, psychological and social factors. This article presents the relevant experimental and clinical recent literature on rehabilitation of erectile function after surgery, external beam radiotherapy, brachytherapy or hormonal deprivation therapy for prostate cancer as it is the most studied model for erectile dysfunction management. Recent findings Counseling and reeducation with a multidisciplinary approach seems to be both mandatory and effective in achieving erectile function recovery. Administration of proerectile drugs nightly or on-demand early after cancer treatment is probably the key factor of erectile rehabilitation. Several studies have highlighted the presumption of a potential role for phosphodiesterase type 5 inhibitors (PDE5-Is) in the prevention of endothelial damage related to ischemia-reperfusion and denervation following surgery or pelvic radiation. Larger multicancer, randomized, controlled trials are needed to assess the role of PDE5-Is in erectile dysfunction pharmacological prophylaxis and rehabilitation strategy. Summary Erectile dysfunction postcancer treatment requires multimodal management with early administration of PDE5-Is, combined therapy to maintain erectile tissue oxygenation if necessary with PDE5-Is, intracavernosal injection and transurethral alprostadil or even vacuum erect device, psychological counseling considering erectile dysfunction as a couples issue. The best modality to optimize postcancer erectile dysfunction management has not yet been standardized and is still challenging.

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: Relationship with prostatic specific antigen immunostain and nuclear DNA content

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Primary Zonal High Intensity Focused Ultrasound for Prostate Cancer: Results of a Prospective Phase IIa Feasibility Study

Aims. In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. Methods. Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5%) was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. Results. A total of 557 men have decided to freeze their semen before cancer treatment. Seminoma was diagnosed in 283 men (54.1%) and nonseminomatous germ cell tumors in 240 men (45.9%). 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. Conclusion. The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.