Prediction models of incontinence and sexual function one year after radical prostatectomy based on data from 20 164 prostate cancer patients.

BACKGROUND: Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool. METHODS: Observational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80-20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models. RESULTS: For model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps.io/EPIC-26-Prediction/. CONCLUSION: The final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients.

Predictors for the utilization of social service counseling by prostate cancer patients.

PURPOSE: Social service counseling (SSC) is an important instrument to support cancer patients, for example, regarding legal support, or rehabilitation. Several countries have established on-site SSC in routine care. Previous analyses have shown that SSC utilization varies across cancer centers. This analysis investigates patient and center-level predictors that explain variations in SSC utilization between centers. METHODS: Logistic multilevel analysis was performed with data from 19,865 prostate cancer patients from 102 prostate cancer centers in Germany and Switzerland. Data was collected within an observational study between July 2016 and June 2020 using survey (online and paper) and tumor documentation. RESULTS: The intraclass correlation coefficient for the null model implies that 51% of variance in SSC utilization is attributable to the center a patient is treated in. Patients aged 80 years and older, with higher education, private insurance, without comorbidities, localized intermediate risk, and undergoing androgen deprivation therapy before study inclusion were less likely to utilize SSC. Undergoing primary radiotherapy, active surveillance, or watchful waiting as compared to prostatectomy was associated with a lower likelihood of SSC utilization. Significant negative predictors at the center level were university hospital, center's location in Switzerland, and a short period of certification. CONCLUSION: The results show that patient and center characteristics contribute to explaining the variance in SSC utilization in prostate cancer centers to a large extent. The findings may indicate different organizational processes in the countries included and barriers in the sectoral structure of the healthcare system. In-depth analyses of processes within cancer centers may provide further insights into the reasons for variance in SSC utilization.

Determinants of self-reported functional status (EPIC-26) in prostate cancer patients prior to treatment.

PURPOSE: The self-reported functional status (sr-FS) of prostate cancer (PCa) patients varies substantially between patients and health-care providers before treatment. Information about this issue is important for evaluating comparisons between health-care providers and to assist in treatment decision-making. There have been few reports on correlates of pretherapeutic sr-FS. The objective of the article, therefore, is to describe clinical and sociodemographic correlates of pretherapeutic sr-FS, based on a subset of the TrueNTH Global Registry, a prospective cohort study. METHODS: A total of 3094 PCa patients receiving local treatment in 44 PCa centers in Germany were recruited between July 2016 and April 2018. Multilevel regression models were applied to predict five pretherapeutic sr-FS (EPIC-26) scores based on clinical characteristics (standard set suggested by the International Consortium for Health Outcomes Measurement), sociodemographic characteristics, and center characteristics. RESULTS: Impaired pretherapeutic sr-FS tended to be associated with lower educational level and poorer disease characteristics-except for "urinary incontinence" which was only associated with age. Notably, age was a risk factor ("urinary incontinence," "urinary irritative/obstructive," "sexual") as well as a protective factor ("hormonal") for pretherapeutic sr-FS. Pretherapeutic sr-FS varies little across centers. CONCLUSIONS: Pretherapeutic sr-FS varies by clinical patient characteristics and age as well as by socioeconomic status. The findings point out the benefit of collecting and considering socioeconomic information in addition to clinical and demographic patient characteristics for treatment decision-making and fair comparisons between health-care providers.

Psychometric validation of the German version of the EPIC-26 questionnaire for patients with localized and locally advanced prostate cancer.

PURPOSE: For patients with prostate cancer, validated and reliable instruments are essential for measuring patient-reported outcomes. The aim of this study was to validate the German version of the widely established Expanded Prostate Cancer Index Composite with 26 items (EPIC-26). METHODS: A German translation of the original questionnaire was tested in 3094 patients with localized or locally advanced (any T, any N and M0) prostate cancer with treatment intent (including radical prostatectomy, brachytherapy, active surveillance, watchful waiting). They completed the EPIC-26 questionnaire before treatment. A total of 521 of them also completed a questionnaire 12 months afterward. Internal consistency, sensitivity to change, and construct validity were assessed. RESULTS: The internal consistency of all domains was sufficient (Cronbach's alpha between 0.64 and 0.93). Item-to-scale correlation coefficients showed acceptable associations between items and their domain score (all > 0.30), with the lowest scores for "bloody stools" (r = 0.37) and "breast problems" (r = 0.32). Confirmatory and exploratory factor analysis confirmed the five-dimension structure of the EPIC-26 (comparative fit index 0.95). CONCLUSIONS: Psychometric evaluation suggests that the German version of the EPIC-26 is a well-constructed instrument for measuring patient-reported health-related symptoms in patients with prostate cancer.

A multicenter paper-based and web-based system for collecting patient-reported outcome measures in patients undergoing local treatment for prostate cancer: first experiences.

PURPOSE: To give an overview of the multicenter Prostate Cancer Outcomes (PCO) study, involving paper-based and web-based collection of patient-reported outcome measures (PROM) in patients undergoing local treatment for prostate cancer in certified centers in Germany. The PCO study is part of the larger Movember-funded TrueNTH Global Registry. The article reports on the study's design and provides a brief progress report after the first 2 years of data collection. METHODS: Prostate cancer centers (PCCs) certified according to German Cancer Society requirements were invited to participate in collecting patient-reported information on symptoms and function before and at least once (at 12 months) after treatment. The data were matched with disease and treatment information. This report describes progress in patient inclusion, response rate, and variations between centers relative to online/paper use, and also data quality, including recruitment variations relative to treatment in the first participating PCCs. RESULTS: PCC participation increased over time; 44 centers had transferred data for 3094 patients at the time of this report. Patient recruitment varied widely across centers. Recruitment was highest among patients undergoing radical prostatectomy. The completeness of the data was good, except for comorbidity information. CONCLUSIONS: The PCO study benefits from a quality improvement system first established over 10 years ago, requiring collection and harmonization of a predefined clinical dataset across centers. Nevertheless, establishing a PROM routine requires substantial effort on the part of providers and constant monitoring in order to achieve high-quality data. The findings reported here may be useful for guiding implementation in similar initiatives.

Is there a need for the Fournier's gangrene severity index? Comparison of scoring systems for outcome prediction in patients with Fournier's gangrene.

UNLABELLED: Study Type - Prognosis (prospective cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Fournier's gangrene (FG) is a rare but life-threatening disease challenging the treating medical staff. Despite the fact that antibiotic therapy combined with surgery and intensive care surveillance are performed as standard treatment, mortality rates remain high. There have been efforts to develop a reliable tool to predict severity of the disease, not only to identify patients at highest risk of major complications or death but also to provide a target for medical teams and researchers aiming to improve outcome and to gather information for counselling patients. Laor et al. published the FG severity index (FGSI) in 1995 presenting a complex prediction score solely for patients with FG. Fifteen years later, Yilmazlar et al. suggested a new and supposedly more powerful scoring system, the Uludag FGSI (UFGSI), adding an age score and an extent of disease score to the FGSI. In the present study population we applied two scoring systems for outcome prediction that are solitarily applicable in patients with FG (FGSI, UFGSI), as well as two general scoring systems such as the established age-adjusted Charlson Comorbidity Index (ACCI) and the recently introduced surgical Apgar Score (sAPGAR) to compare them and to test whether one system might be superior to the other. In addition, we identified potential prognostic factors in the study population. By contrast to many earlier studies, we performed a combined prospective and retrospective analysis and provided a 30-day follow up. In the cohort of the present study, older patients with comorbidities as well as a need for mechanical ventilation and blood transfusion are at higher risk of lethal outcome. All scores are useful to predict mortality. Despite including more variables, the UFGSI does not seem to be more powerful than the FGSI. In daily routine we suggest applying ACCI and sAPGAR, as they are more easily calculated, generally applicable and well validated. OBJECTIVE: • To compare four published scoring systems for outcome prediction (Fournier's gangrene severity index [FGSI], Uludag FGSI [UFGSI], age-adjusted Charlson Comorbidity Index [ACCI] and surgical Apgar Score [sAPGAR]) and evaluate risk factors in patients with Fournier's gangrene (FG). PATIENTS AND METHODS: • In all, 44 patients were analysed. The scores were applied. • A Mann-Whitney U-test, Fisher's exact test, receiver operator characteristic (ROC) analysis and Pearson correlation analysis were performed. RESULTS: • The results of the present study show a significant association among FGSI (P= 0.002), UFGSI (P= 0.002), ACCI (P= 0.004), sAPGAR (P= 0.018) and death. • The differences between the area under the receiver operating characteristic curve of the scores were not significant. • Non-survivors were older (P= 0.046), had a greater incidence of acute renal failure (P < 0.001) and coagulopathy (P= 0.041), were treated more often with mechanical ventilation (P= 0.001) and received more packed red blood cells (RBCs; P= 0.001). CONCLUSION: • Older patients with comorbidities and need for mechanical ventilation and RBCs are at higher risk for death. • In the present cohort, scores calculated easily at the bedside, such as ACCI and sAPGAR, seemed to be as good at predicting outcome in patients with FG as FGSI and UFGSI.

Observation of de novo bladder dysfunction under treatment with Her2-neu antibodies.

PURPOSE: We diagnosed de novo bladder dysfunction in several breast cancer patients under cancer-specific therapy with trastuzumab. The goal of this retrospective analysis was to investigate whether bladder dysfunction is common in a larger population of breast cancer patients receiving trastuzumab therapy. PATIENTS AND METHODS: We identified 93 patients who received at least two doses of trastuzumab at our institution in the years 2003-2006. 57 of those patients were still alive at the time of this analysis. We mailed a validated global questionnaire for the assessment of incontinence (King's Health Questionnaire, KHQ) to them, additionally asking for bladder dysfunction observed under trastuzumab therapy. RESULTS: 43 (75%) of the patients returned the questionnaire, 11 (25%) of them reporting severe de novo bladder dysfunction under therapy. Significant differences between symptomatic and asymptomatic patients were detected in all KHQ subscales. Previous conditions and surgeries as well as medications, especially hormonal therapy, were excluded as underlying causes. However, there were more patients under taxane-based chemotherapy in the symptomatic group. CONCLUSIONS: The epidermal growth factor receptor is involved in the cellular response to mechanical stretch in the urinary bladder. Based on our findings, we hypothesize that interfering with this pathway may well be the cause of symptomatic bladder dysfunction in patients under trastuzumab medication. A prospective study is required to further elucidate this hypothesis.

The impact of prostate biopsy and periprostatic nerve block on erectile and voiding function: a prospective study.

PURPOSE: We evaluated the effect of multiple core prostate biopsy and periprostatic nerve block on voiding and erectile function. MATERIALS AND METHODS: A total of 198 patients in whom prostate cancer was suspected were randomly assigned to undergo 10-core prostate biopsy with (71) or without (74) periprostatic nerve block. The 53 men with a history of negative prostate biopsy underwent 20-core saturation prostate biopsy with periprostatic nerve block. The International Prostate Symptom Score and International Index of Erectile Function were completed before, and 1, 4 and 12 weeks after biopsy to measure changes in voiding and erectile function, and quality of life. Upon prostate cancer diagnosis patients were excluded from further analysis. RESULTS: The International Prostate Symptom Score was significantly increased in all patients at week 1, which persisted at weeks 4 and 12 after saturation biopsy (p = 0.007 and 0.035, respectively). After 10-core prostate biopsy with periprostatic nerve block patients had a higher International Prostate Symptom Score at weeks 4 and 12 but this was not statistically significant (p >0.05). Quality of life was significantly affected at all times after saturation prostate biopsy (p = 0.001, 0.003 and 0.010, respectively). International Index of Erectile Function scores decreased significantly in all groups at week 1 (p <0.05). The decrease persisted at week 4 in each 10-core prostate biopsy group. CONCLUSIONS: Prostate biopsy causes impaired voiding. Saturation prostate biopsy and periprostatic nerve block seem to have a lasting impact on voiding function. Erectile function is transiently affected by prostate biopsy regardless of periprostatic nerve block and the number of cores. Patients who undergo prostate biopsy must be informed about these side effects.

The first description of an extramedullary plasmacytoma of the ureter.

Causes for acquired unilateral obstruction of the ureter are numerous: calculi, infections, blood clots and tumors are the most common underlying pathologies. Hematologic tumors with initial clinical manifestation in the lower urinary tract are rare. Primary localization of plasmocytoma has been described in kidney, bladder and urethra. Herein, we describe the first manifestation of a primary solitary extramedullary plasmacytoma of the ureter. The tumor was discovered upon diagnostic workup of gross hematuria and asymptomatic hydronephrosis. Thus far, after radical surgery the patient remains free of disease.

Open radical retropubic prostatectomy gives favourable surgical and functional outcomes after transurethral resection of the prostate.

OBJECTIVES: To assess the peri- and postoperative outcome of patients treated with open radical retropubic prostatectomy (RRP) for prostate cancer and who had previously undergone transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Prospectively collected data from a consecutive series of 1760 patients who had RRP between July 2003 and June 2007 at our institution were used to retrospectively match 62 cases (with previous TURP) with the same number of controls (without previous TURP). Matching variables were patient age, body mass index, prostate volume, preoperative total prostate-specific antigen (PSA) level, Gleason score, pathological stage, and intraoperative nerve-sparing procedure. Complete 1-year follow-up data were available for all patients. All collected data on surgery and perioperative complications were analysed. Functional outcome data at the 1-year follow-up were evaluated by applying an institutional questionnaire. Sexual function was assessed using the abbreviated International Index of Erectile Function-5 questionnaire, and urinary control was evaluated by defining complete urinary control as no pad usage. RESULTS: The rate of complete urinary control rate in cases and controls was similar (81% vs 82%). When nerves were spared, 60% (15/25) of patients in either group were capable of sexual intercourse. The overall positive surgical margin rate was insignificantly higher in cases (19% vs 13, P>0.05). After 1 year of follow-up the biochemical recurrence rate (PSA>0.04 ng/mL) did not differ significantly in patients who had RRP after TURP vs RRP alone (six of 62, 10%, vs five of 62, 8%; P=0.77). CONCLUSIONS: RRP for prostate cancer in patients who have had previous TURP does not result in a higher perioperative complication rate, or a worse functional outcome.

Bullous pemphigoid is a rare paraneoplastic syndrome in patients with renal cell carcinoma.

Renal cell carcinoma is associated with paraneoplastic syndromes in up to 40% of cases. Dermatological manifestations are rare. A case of a bullous pemphigoid as a paraneoplastic symptom was diagnosed in a 52-year-old patient with a partially sarcomatoid papillary renal cell carcinoma.

Identification of bladder cancer patients at risk for recurrence or progression: an immunohistochemical study based on the expression of metallothionein.

Despite similarities in tumor stage and grade the individual outcome of bladder cancer patients is not predictable. The ideal tool for treatment stratification has not yet been found. Metallothionein (MT) overexpression is correlated with poor tumor differentiation, resistance to chemotherapy, and impaired survival in different malignancies. The clinical relevance of MT expression for defining patients at high risk for recurrence or progression was assessed. MT was detected immunohistochemically and evaluated semiquantitively in tumor specimens of 103 male and 19 female patients (transsurethral resection: n = 94, cystectomy: n = 28). Mean age of the patients was 68 (38-87) yr. According to histopathological features, three groups were distinguished for further analysis (pTa-1G1-2, pTis/pT1G3, and muscle invasive tumors). A cutoff value of 50% immunoreactive cells was used for further analysis. The 5-yr tumor specific survival rate was significantly lower in patients with high MT expression (32 vs. 72%). Accordingly, impaired 5-yr recurrence (90 vs. 58%), and progression rates (78 vs. 54%) were associated with high MT expression. All patients suffering from pTis and pT1G3 tumors with MT expression above the cutoff value showed recurrence within less than 40 mo, whereas 26% of those patients with MT expression below the cutoff value remained long-term recurrence free. Long term progression free survival was detected in 75% of pT1G3 patients with MT expression below the cutoff value. In contrast, 68% of pT1G3 tumor patients with MT expression above the cutoff value progressed, all within the first 12 mo after initial tumor resection. A correlation between high MT expression and prognosis was demonstrated especially in pT1G3 and pTis tumors, where >50% MT expression was linked to shorter tumor-specific survival and increased recurrence/progression rates. Thus, MT expression seems to be a promising marker for further risk stratification in the clinical treatment of bladder cancer patients.

Clinical usefulness of urodynamic assessment for maintenance of bladder function in patients with spinal cord injury.

AIMS: The vast majority of spinal cord lesions cause neurogenic bladder disorders. Detrusor hyperreflexia presents a major risk factor for renal damage in these patients. We evaluated the long-term results of patients with spinal cord injury treated at our institution. METHODS: Eighty spinal cord injury patients (60 male, 20 female; mean age 29.6 years) with at least one follow-up visit a year for a minimum of five consecutive years, were included in this retrospective analysis. Follow-up included urodynamic evaluation, sonography of the upper and lower urinary tract, urine examination, and evaluation of renal function. Treatment modifications were based on the urodynamic findings. RESULTS: Mean follow-up was 67.3 months (range 60-103 months). At initial presentation, 51 patients performed intermittent catheterization, 7 had indwelling catheters, 10 utilized reflex voiding, 2 patients presented with a Brindley stimulator, 10 patients used abdominal straining. At the end of our study, no patient had signs of renal damage. To achieve that goal, 8 patients underwent sphincterotomy, 3 received a Brindley stimulator, 3 underwent bladder augmentation, one Kock pouch was performed, and 12 patients were treated with botulinum-A-toxin injections in the detrusor. Twenty-two patients received intravesical anticholinergic therapy. In merely three patients, treatment was not modified during the entire follow-up. CONCLUSIONS: In the long term, treatment strategy of neurogenic bladder dysfunction in patients with spinal cord injury had to be modified in almost all patients. 18.8% underwent surgery. For protection of the upper urinary tract and maintenance of continence, regular urodynamic follow-up is warranted.

Muscle fibrillation as a sign of electrode damage in sacral neuromodulation.

Sacral root neuromodulation is recognized as an effective therapy for chronic voiding dysfunction. However, knowledge about the neuromodulator in the general medical community is scarce. We report a case of muscle fibrillation caused by current leaking from a neuromodulator lead which had been damaged during disc prolapse surgery.

Bacterial contamination of test stimulation leads during percutaneous nerve stimulation.

OBJECTIVES: To analyze the bacterial contamination of conventional percutaneous nerve stimulation (PNE) leads. Sacral neuromodulation has become an important tool for the treatment of urgency and chronic retention. Patients likely to benefit from this type of therapy are identified by PNE testing before implantation of the definitive system. Recently, a new system was introduced, using a self-blocking electrode that remains in place for both PNE testing and final implantation. PNE testing warrants an extracorporeal stimulator. Thus, using the same electrode for both external stimulation and definitive implantation may carry a significant risk of infection. METHODS: Bilateral PNE testing was performed in 11 consecutive patients (8 women and 3 men, mean age 41.6 years) for either urgency (n = 7) or chronic retention (n = 4). Electrodes were placed under aseptic conditions and stimulated for 3 days. At the end of each test, the electrodes were removed and evaluated microbiologically. RESULTS: In 5 of the 11 patients (9 of 22 leads), significant bacterial growth was detected: Staphylococcus epidermidis in 5, Escherichia coli in 3, and Enterococcus faecalis in 1. However, no patient showed signs of inflammation at the electrode insertion sites. CONCLUSIONS: Bacterial growth was found in 45.5% of the patients after conventional PNE testing under aseptic conditions. Therefore, the new electrodes may well carry an elevated risk of infection. Infection of the implant can lead to major surgical revision or even explantation. Thus, additional studies of the infection risk of this new electrode are warranted before its general use can be recommended.

Transient ischemic attack after electromotive drug administration for chronic non-infectious cystitis: report of two similar cases.

UNLABELLED: Electromotive drug administration (EMDA) is a new and promising approach for the treatment of chronic non-infectious cystitis. In animal studies utilizing EMDA there was evidence for deep penetration of dyes into the muscular layers of the bladder wall. However, besides minor local irritation no systemic side effects have been reported after translation of EMDA into the clinical setting. AIMS: This article reports for the first time systemic neurological alterations after EMDA for chronic non-infectious cystitis. SUBJECTS AND METHODS: Two male patients, aged 72 and 78 years, respectively, were readmitted to the emergency room within few hours after EMDA showing clinical signs of transient ischemic attacks (TIA). After clinical examination, both patients were observed. RESULTS: Under overnight observation without any specific therapy the symptoms vanished completely in both patients. CONCLUSIONS: In older patients (>70 years of age) undergoing EMDA, cardiac and neurologic function should be monitored. The time of treatment during the first EMDA session should be limited to 15 or 20 min.

A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma.

Cultured tumor lysate-loaded dendritic cells (TuLy-DC) have been demonstrated in vitro to stimulate potent immune modulations and generate significant antitumor response. We report the results of a pilot trial of TuLy-DC vaccine for patients with metastatic renal cell carcinoma (mRCC). Fourteen mRCC patients underwent nephrectomy to obtain autologous TuLy prepared by subjecting tumor cells to 3 freeze/thaw cycles. Dendritic cells were generated from peripheral blood CD14+ precursors cultured in the presence of GM-CSF, IL-4, and 10% autologous serum. Patients received one vaccination of TuLy alone as an immunologic control, followed by 3 weekly vaccinations of DC-TuLy injected intradermally in the midaxillary region. Peripheral blood lymphocytes were collected before and after weekly vaccines and were assessed for changes in phenotype, cytotoxicity, and cytokine profile. The TuLy-DC vaccine was successfully prepared and administered to 12 patients, whereas 2 patients did not receive vaccine treatment due to declines in postoperative performance status. The vaccines were well tolerated, with only grade 1 toxicities noted. One patient had a partial response to treatment that did not correspond to any significant change in immunologic profile. This pilot trial demonstrated both the safety and feasibility of reliably preparing a DC-based vaccine for mRCC patients. Our data suggest that autologous TuLy-DC vaccines generate only limited clinical response. Further clinical studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response in vivo.