Patient Benefits of Radical Prostatectomy in Certified Prostate Cancer Centers: Comparative Results from the Multicenter IMPROVE Study.

INTRODUCTION: We investigated differences in treatment outcomes following radical prostatectomy (RP) between certified centers (CCs) and noncertified centers (nCCs) within the IMPROVE study group. METHODS: A validated survey assessing various factors, including stress urinary incontinence (SUI) and decision regret (DR), was administered to 950 patients who underwent RP across 19 hospitals (12 CCs and 7 nCCs) at a median follow-up of 15 months after RP (interquartile range: 11-20). The response rate was 74%, with 703 patients participating, including 480 (68%) from CCs. Multivariate binary regression models were used to analyze differences between CCs and nCCs regarding the following binary endpoints: nerve-sparing (NS), positive surgical margins (PSM), SUI (defined as >1 safety pad), complications based on the Clavien-Dindo classification (grade ≥1, grade ≥3) and DR (>15 points indicating critical DR). RESULTS: Considering the multivariate analysis, the rate of NS surgery was lower in CCs than in nCCs (OR = 0.52; p = 0.004). No significant differences were observed in the PSM rate (OR = 1.67; p = 0.051), SUI (OR = 1.03; p = 0.919), and DR (OR = 1.00; p = 0.990). SUI (OR 0.39; p < 0.001) and DR (OR 0.62; p = 0.026) were reported significantly less frequently by patients treated with robotic-assisted RP, which was significantly more often performed in CCs than in nCCs (68.3% vs. 18%; p < 0.001). The total complication rate was 45% lower in CCs (OR = 0.55; p = 0.004), although the number of complications requiring intervention (Clavien-Dindo classification ≥3) did not differ significantly between CCs and nCCs (OR = 2.52; p = 0.051). CONCLUSION: Within the IMPROVE study group, similarly favorable outcomes after RP were found in both CCs and nCCs, which, however, cannot be transferred to the general treatment landscape of PCA in Germany. Of note, robotic-assisted RP was more often performed in CCs and associated with less SUI and DR, while open prostatectomy was the treatment of choice in low-volume nCCs. Future prospective and region wide studies should also investigate the surgeon caseload and experience as well as a spillover effect of the certification process on nCCs.

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance.

PURPOSE: The antibody-drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients with metastatic urothelial carcinoma (mUC) without prior assessment of the tumor receptor status as ubiquitous NECTIN-4 expression is assumed. Our objective was to determine the prevalence of membranous NECTIN-4 protein expression in primary tumors (PRIM) and patient-matched distant metastases (MET). EXPERIMENTAL DESIGN: Membranous NECTIN-4 protein expression was measured (H-score) by IHC in PRIM and corresponding MET (N = 137) and in a multicenter EV-treated cohort (N = 47). Progression-free survival (PFS) after initiation of EV treatment was assessed for the NECTIN-4-negative/weak (H-score 0-99) versus moderate/strong (H-score 100-300) subgroup. The specificity of the NECTIN-4 IHC staining protocol was validated by establishing CRISPR-Cas9-induced polyclonal NECTIN-4 knockouts. RESULTS: In our cohort, membranous NECTIN-4 expression significantly decreased during metastatic spread (Wilcoxon matched pairs P < 0.001; median H-score = 40; interquartile range, 0-140), with 39.4% of MET lacking membranous NECTIN-4 expression. In our multicenter EV cohort, absence or weak membranous NECTIN-4 expression (34.0% of the cohort) was associated with a significantly shortened PFS on EV (log-rank P < 0.001). CONCLUSIONS: Membranous NECTIN-4 expression is frequently decreased or absent in mUC tissue. Of note, the clinical benefit of EV strongly depends on membranous NECTIN-4 expression. Thus, our results are of highest clinical relevance and argue for a critical reconsideration of the current practice and suggest that the NECTIN-4 receptor status should be determined (ideally in a metastatic/progressive lesion) before initiation of EV. See related commentary by Aggen et al., p. 1377.

Patients Regret Their Choice of Therapy Significantly Less Frequently after Robot-Assisted Radical Prostatectomy as Opposed to Open Radical Prostatectomy: Patient-Reported Results of the Multicenter Cross-Sectional IMPROVE Study.

Patient's regret (PatR) concerning the choice of therapy represents a crucial endpoint for treatment evaluation after radical prostatectomy (RP) for prostate cancer (PCA). This study aims to compare PatR following robot-assisted (RARP) and open surgical approach (ORP). A survey comprising perioperative-functional criteria was sent to 1000 patients in 20 German centers at a median of 15 months after RP. Surgery-related items were collected from participating centers. To calculate PatR differences between approaches, a multivariate regressive base model (MVBM) was established incorporating surgical approach and demographic, center-specific, and tumor-specific criteria not primarily affected by surgical approach. An extended model (MVEM) was further adjusted by variables potentially affected by surgical approach. PatR was based on five validated questions ranging 0−100 (cutoff >15 defined as critical PatR). The response rate was 75.0%. After exclusion of patients with laparoscopic RP or stage M1b/c, the study cohort comprised 277/365 ORP/RARP patients. ORP/RARP patients had a median PatR of 15/10 (p < 0.001) and 46.2%/28.1% had a PatR >15, respectively (p < 0.001). Based on the MVBM, RARP patients showed PatR >15 relative 46.8% less frequently (p < 0.001). Consensual decision making regarding surgical approach independently reduced PatR. With the MVEM, the independent impact of both surgical approach and of consensual decision making was confirmed. This study involving centers of different care levels showed significantly lower PatR following RARP.

Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment.

INTRODUCTION: Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. MATERIALS AND METHODS: To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. RESULTS: A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. CONCLUSION: While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

[Guidelines for consultations regarding incontinence care products]. / Leitlinie Hilfsmittelberatung bei Harninkontinenz.

An investigation of the German consumer organisation "Stiftung Warentest" in 2017 confirmed significant deficiencies in the information, advice and supply of incontinence care products received by urinary incontinence patients. The German Society of Urology (DGU) thereupon drafted and later published guidelines concerning the consultation of patients in the context of incontinence care. Important aspects of the consultation process include the determination of the type of incontinence as well as its severity, clinical examination, and advice regarding possible curative treatments. However, the advice appointment takes centre stage and should ideally be conducted by a qualified person in a separate room granting sufficient privacy and time. Furthermore, repeated supply of a selection of samples for differing degrees and types of incontinence, accommodating the patient's individual preferences and anatomical features, is crucial in order to ensure optimal incontinence care. In the case of commercial health care service providers, transparency relating to the financial implications of e.g. expensive products is key, which is what has been intended by German health insurance providers. The new guidelines concerning urinary incontinence care consultation constitute a step towards the improvement and structuring of processes in the consultation regarding, and the supply of, incontinence care products.

To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic.

INTRODUCTION: After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. RESULTS: 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits. CONCLUSION: The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

Switching from Endoscopic Extraperitoneal Radical Prostatectomy to Robot-Assisted Laparoscopic Prostatectomy: Comparing Outcomes and Complications.

OBJECTIVE: Endoscopic extraperitoneal radical prostatectomy (EERPE) and robot-assisted laparoscopic prostatectomy (RALP) are minimally invasive surgical techniques to treat localized prostate cancer. We report the outcome and complications of these two techniques conducted by one individual surgeon. PATIENTS AND METHODS: 86 patients underwent EERPE between January 2008 and June 2011, and 100 patients underwent RALP between August 2011 and October 2012. All surgeries were performed by one single surgeon. RESULTS: The patients of the EERPE and RALP groups had similar clinical characteristics in PSA, prostate volume and D'Amico classification, and were significantly different in their age and BMI as well as in the number of prior surgeries. RALP surgeries were significantly slower (183 vs. 157 min) but also involved lower blood loss (147 vs. 245 ml). Pathological stages and positive surgical margins were similar in both groups. Complications were assessed by the Clavien-Dindo classification. 6 patients in the EERPE group and 3 patients of the RALP group suffered major complications (IIIb-IV). CONCLUSION: Altogether our results indicate that the learning curve for RALP was short after experience with EERPE. We hypothesize that this is more a result of the surgical experience of the surgeon with the EERPE than on the robotic technique.

Penile cancer--prevention and premalignant conditions.

OBJECTIVES: Relatively little evidence is available in the published studies on the prevention of penile cancer and premalignant conditions of the penis. The present review examined the current evidence available in preventing penile cancer and pathologic subtypes of premalignant conditions and their treatment. The recommendations made in the present review formulate the basis of the recent 2009 International Consultation on Urologic Disease Consensus Publishing Group. METHODS: The association of human papillomavirus subtypes and penile cancer is well-established, although the etiology, natural history, and treatment of premalignant lesions have mainly been reported in retrospective case series with short-term follow-up. The exact pathologic role of chronic inflammatory conditions, such as balanitis xerotica obliterans in the etiology of penile cancer remains largely unknown. RESULTS: Some of the potential strategies for the prevention of penile cancer could include circumcision, reducing the risk of transmission of penile human papillomavirus infection with male vaccination, early treatment of phimosis, smoking cessation, and hygienic measures. Implementing some of these measures would require extensive cost/benefit analysis, with significant changes in the global health policy. CONCLUSIONS: Owing to the current levels of evidence from published studies, firm guidelines cannot be formulated for the treatment of premalignant conditions, although preventative measures, such as reducing human papillomavirus transmission, could become strategic health targets.

Nephron-sparing surgery for renal cell carcinoma in the solitary kidney.

OBJECTIVE: Partial nephrectomy in solitary kidneys carries the risk of tumour progression as well as loss of renal function. We evaluated complications and outcome in patients with renal cell cancer in solitary kidneys who were treated by means of nephron-sparing surgery. MATERIAL AND METHODS: Between 1993 and 2003, 38 patients with renal cell carcinoma in a solitary kidney underwent nephron-sparing surgery (partial nephrectomy, n = 37; work-bench resection, n = 1). Of these patients, 21 had asynchronous and eight had synchronous bilateral tumours and underwent contralateral radical nephrectomy. The variables examined were tumour size, disease progression, pre- and postoperative renal function and early (within 30 days of nephron-sparing surgery) and late complications. RESULTS: After a mean follow-up period of 41.7 months (range 8-93 months) the mean serum creatinine level had increased from 1.25 mg/dl preoperatively to 1.62 mg/dl postoperatively. Seventeen patients retained normal renal function and 21 developed some degree of renal insufficiency. New-onset chronic renal insufficiency after nephron-sparing surgery with creatinine levels >2 mg/dl was the only late complication observed, occurring in 10 cases. None of the patients required dialysis. Transient urinary leakage was the most frequent early complication, occurring in four cases. Recurrence and/or progression were seen in six patients: four with local recurrence (three of whom also had distant metastases) and two with pure metastatic progression. Nephron-sparing surgery was repeated for the patient with isolated local tumour recurrence. The mean tumour size was 3.8 cm (range 0.7-9.9 cm). Tumour size was markedly greater in patients who developed disease progression (6.2 vs 3.5 cm) and in those who developed renal insufficiency (5.2 vs 3.3 cm). CONCLUSIONS: Nephron-sparing surgery for renal cell carcinoma involving a solitary kidney provides effective curative treatment for small tumours, with preservation of renal function. However, patients who undergo partial nephrectomy for locally extensive tumours are at high risk of disease progression.

Comparison of transperitoneal versus retroperitoneal approach in laparoscopic radical nephrectomy for renal cell carcinoma: a single-center experience of 63 cases.

BACKGROUND: We report our experience with the retroperitoneal (RP) and transperitoneal (TP) approaches for laparoscopic nephrectomy for clinically localized renal cell carcinoma. METHODS: Sixty-three patients with renal cell carcinoma were treated with laparoscopic nephrectomy, 34 by TP and 29 by RP approach between June 1999 and June 2003. Average age, ASA score, tumor stage and tumor size were similar in both groups. Early complications within 30 days and surgical time were retrospectively reviewed. RESULTS: Surgical time was with a mean of 183 and 190 minutes equal for the TP and RP approach. Intraoperative complications occurred in 4 patients and were vascular, requiring blood transfusion in 2 patients each per group. Postoperative complications were thromboembolism in 1 patient and subcutaneous seroma in 1 patient, both in the TP group. CONCLUSIONS: Although the sample size is small, it appears that the tumor control and surgical time in laparoscopic nephrectomy are not significantly influenced by the approach.

Intraluminal tumour thrombus of a mixed non-seminomatous germ cell tumour of testis within the inferior vena cava.

BACKGROUND: Intracaval tumour thrombus developed per continuitatem from a primary testicular tumour is rare. CASE REPORT: A patient with metastatic mixed non-seminomatous germ cell tumour of the testis extending into the inferior vena cava (IVC) is presented. He belonged to the intermediate-risk group according to the IGCCCG (International Germ Cell Cancer Collaborative Group) classification. The 26-year-old man underwent right inguinal orchiectomy. Computed tomography revealed the tumour thrombus as filling defect in the IVC extending nearly to the right renal vein. Duplex sonography detected a partial thrombosis of the IVC. Combination chemotherapy led to regression of pulmonal metastases and the intraluminal tumour thrombus. 5 months later, retroperitoneal lymphadenectomy was performed and the intraluminal thrombus was extracted by cavotomy. The thrombus originated from the ostium of the right testicularis vein in the IVC. Histological examination revealed no vital tumour tissue. CONCLUSION: In patients with testicular cancer information about pathological processes of the IVC is important for therapeutic management. Testicular tumours seldom extend up the IVC.

Adult prostate sarcoma diagnosed from tissue spontaneously excreted through the urethra.

The diagnosis of soft tissue tumors based on small tissue samples may be difficult. We report on an organ confined prostate sarcoma in an adult primarily diagnosed in a small piece of tissue, which spontaneously passed the urethra during voiding.

Large solitary fibrous tumor of the seminal vesicle.

Solitary fibrous tumors show a classic morphologic pattern ("patternless pattern") consisting mainly of a proliferation of bland spindle cells with varying amounts of thick, often hyalinized or keloid-like, intercellular collagen bundles. Immunohistochemistry shows a strong reactivity for CD34 antigen, vimentin, and, in a variable percentage, bcl-2 antigen. We report the case of a 50-year-old man with a large solitary fibrous tumor located in the pelvic cavity with a rare nonspecific histologic pattern of pseudovascular formations. The patient underwent pelvic exenteration with orthotopic continent urinary diversion and sigmoid-J-pouch bowel reconstruction. No signs of tumor recurrence were noted within 24 months of surgery.

Preoperative cardiopulmonary risk assessment as predictor of early noncancer and overall mortality after radical prostatectomy.

OBJECTIVES: To evaluate the capability of the preoperative cardiopulmonary risk assessment to predict early noncancer and overall mortality after radical prostatectomy for clinically localized prostate cancer. METHODS: In 444 consecutive radical prostatectomy patients, the American Society of Anesthesiologists Physical Status classification and the presence of cardiac insufficiency (New York Heart Association classification), angina pectoris (Canadian Cardiovascular Society classification), diabetes, hypertension, history of thromboembolism, and chronic obstructive or restrictive pulmonary disease were assessed. Kaplan-Meier time-event curves and Mantel-Haenszel hazard ratios were estimated for noncancer (other deaths were censored) and overall mortality. Cox proportional hazard models were used to analyze possible combined effects of risk factors. RESULTS: During an average follow-up of 4.7 years, 36 patients died: 15 of noncancer causes, 14 of prostate cancer, 6 of other cancers, and 1 in a car accident. The comorbidity scores for American Society of Anesthesiologists Physical Status classification, New York Heart Association classification, and Canadian Cardiovascular Society classification and combinations between the latter two scores were significantly associated with early noncancer mortality in a dose-response pattern. Furthermore, patients with chronic obstructive pulmonary disease were at increased risk. The association with overall mortality was less strong. CONCLUSIONS: The preoperative cardiopulmonary risk assessment may be used as a predictor of early noncancer and overall mortality after radical prostatectomy and should be evaluated further as a source of prognostic information in surgical oncology.

Distal ureteral stenosis after early adjuvant intravesical mitomycin C application for superficial bladder cancer.

We report a case of distal ureteral stenosis after transurethral resection of a small bladder tumor near the left ureteral orifice and early postoperative mitomycin C instillation for prevention of recurrence. The patient developed late recurrent stenosis of the ureteral orifice with histologic evidence of localized, severe benign inflammatory reaction. The recurrent stenosis was successfully managed by transurethral resection of the scar tissue and ureteric stenting. Although ureteral stenosis does occur after transurethral resection, the severity and time course of the stenosis in this case suggest an influence of the intravesical chemoprophylaxis used.

Evaluation of chemical composition of urinary calculi by conventional radiography.

BACKGROUND AND PURPOSE: The choice of the most efficient treatment modality for renal calculi could be facilitated by determining the precise chemical stone composition before treatment. We investigated the possibility of using conventional X-ray imaging to determine stone composition and to find a simple method of predicting stone fragility for treatment planning. MATERIALS AND METHODS: The X-ray density of 92 stones with known infrared spectroscopy analyses (calcium oxalate monohydrate, calcium oxalate dihydrate, struvite, and calcium phosphate) was retrospectively investigated by scanning the films with a digital camera. The data analysis was done using a commercially available graphics program to compare the total gray-scale levels of the stones. RESULTS: There was a significant difference in the mean gray-scale level of calcium phosphate and calcium oxalate stones (P < 0.01). The mean gray-scale difference between calcium oxalate dihydrate and calcium oxalate monohydrate was also significant (p < 0.02). All calcium oxalate, struvite, and calcium phosphate stones were correctly identified. Of the calcium oxalate monohydrate and calcium oxalate dihydrate stones, 98.4% and 66.6%, respectively, were correctly identified. CONCLUSION: The method allows a reliable diagnosis of stone composition from radiographs, which can be useful in stone treatment planning.

Outcome of surgical treatment of isolated local recurrence after radical nephrectomy for renal cell carcinoma.

PURPOSE: Isolated local recurrences after radical nephrectomy for renal cell carcinoma occur in 2% to 3% of cases. Today local recurrences can be detected at an early stage due to modern imaging techniques. It remains controversial whether an aggressive surgical approach to this problem can prolong survival. MATERIALS AND METHODS: We retrospectively analyzed 16 patients who were treated surgically at our institution for suspected isolated local renal cell carcinoma recurrence during the last 10 years. All patients had undergone extensive staging and had no evidence of distant metastases with the local recurrence. Surgical exploration confirmed carcinoma recurrence in 13 of the 16 cases and all 13 patients underwent complete resection of the local recurrence. Three patients were found to have had false-positive computerized tomography findings on surgical exploration. RESULTS: Mean time to recurrence was 45.5 months (range 7 to 224). Only 2 patients were symptomatic, while in 11 disease had been detected at routine followup. Mean size of the recurrent tumor was 5.92 cm. (range 2 to 10). All patients survived surgery without major complications. Of the patients 7 died of metastatic disease after a mean survival of 23.1 months (range 4 to 68) following recurrence removal and 6 are alive with a mean survival of 53.0 months (range 18 to 101) (p = 0.09). Time to recurrence after nephrectomy was significantly longer (p <0.05) and size of recurrence significantly smaller (p <0.04) in the patients still alive. In 1 surviving patient evidence of metastatic disease developed 9 months after surgery for recurrence. CONCLUSIONS: Careful followup after radical nephrectomy for renal cell carcinoma allows the diagnosis of small local recurrences before they become symptomatic in the majority of cases. Although most of these patients will eventually have and die of metastatic disease, an aggressive surgical approach is justified and can result in prolonged survival.

Diagnostic value of 18F-FDG positron emission tomography for detection and treatment control of malignant germ cell tumors.

INTRODUCTION: The role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is currently under evaluation in urologic oncology. The aim of the present study was to investigate the use of [18F]FDG positron emission tomography ([18F]FDG-PET) in the detection and treatment control of malignant germ cell tumors compared to computed tomography (CT). MATERIALS AND METHODS: Thirty-two PET studies and CT scans were carried out in 23 patients with histologically proven germ cell tumors (10 seminomas, 12 non-seminomatous germ cell tumors (NSGCT), 1 unclassified serologic recurrent disease) Lugano stage I-III. The scans were done either after initial diagnosis (n = 21) and/or within 3-45 days after chemotherapy was completed (n = 11). PET and CT were validated either by histology (n = 7) or clinical follow-up of 6-11 months after the last PET study has been performed (n = 16). Sensitivity, specificity, accuracy, positive and negative predictive values were determined for PET and CT. Differences between PET and CT for parameters of diagnostic value were evaluated by chi(2) test. RESULTS: Although not statistically significant, the sensitivity, accuracy and negative predictive value were higher for PET than for CT with respect to the detection of metastatic infradiaphragmatic and supradiaphragmatic lesions after initial diagnosis. The specificity and positive predictive value of PET and CT were comparable. After chemotherapy, PET was found to be significantly superior in specificity and accuracy compared to CT with respect to infradiaphragmatic lesions (p < 0.05). False-positive PET findings in supradiaphragmatic lesions after chemotherapy occurred in the case of inflammatory processes and resulted in a loss of specificity and accuracy compared to CT (p < 0.05). CONCLUSIONS: These preliminary results demonstrate [18F]FDG-PET to be a useful diagnostic tool for the initial staging and treatment control in patients with germ cell tumors. Possible advantages compared to CT, however, are as yet not clearly defined. The possibility of false-positive PET findings due to reactive supradiaphragmatic inflammatory processes early after chemotherapy have to be considered.