Short-term Changes in Health-related Quality of Life of Patients Undergoing Radical Surgery for Upper Urinary Tract Urothelial Carcinoma: Results from a Prospective Phase 2 Clinical Trial.

Background and objective: The possible negative impact of radical surgery on patients' health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes. Methods: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds. Key findings and limitations: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning. Conclusions and clinical implications: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery. Patient summary: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery.

The accuracy of cystoscopy in predicting muscle invasion in newly diagnosed bladder cancer patients.

PURPOSE: The prognosis of muscle-invasive bladder cancer (MIBC) has not improved for three decades. Transurethral resection of the bladder tumor (TURBT) is the standard procedure for local tumor staging. TURBT has several limitations, including the spread of tumor cells. Therefore, an alternative is needed in patients with suspected MIBC. Recent studies have shown that mpMRI is very accurate in staging bladder tumors. Because the diagnostic efficacy of urethrocystoscopy (UCS) has been reported as good as the efficacy of mpMRI to predict muscle invasion we performed this prospective multicenter study in which we compare UCS with pathology. METHODS: From July 2020 until March 2022, 321 patients with suspected primary BC in seven participating Dutch hospitals were included in this study. A flexible UCS was performed by urologists, physician assistants, or residents. Predictions of muscle invasion using a 5-point Likert scale alongside the histopathology data were recorded. The sensitivity, specificity, predictive values, and 95% confidence intervals were determined using a standard contingency table. RESULTS: Of the 321 included patients, 232 (72.3%) received a histopathological diagnosis of non-muscle-invasive bladder cancer (NMIBC) and 71 (22.1%) were histopathologically diagnosed as MIBC. In 2 patients (0.6%), classification was not possible (Tx). Cystoscopy predicted muscle invasion with a sensitivity of 71.8% (95% CI 59.9-81.9), and a specificity of 89.9% (95% CI 85.4-93.3). This corresponds to a positive predictive value (PPV) of 67.1% and a negative predictive value (NPV) of 91.7%. CONCLUSION: Our study shows a moderate accuracy of cystoscopy to predict muscle invasion. This result does not support the use of cystoscopy only instead of TURBT for local staging.

3-D and 2-D reconstruction of bladders for the assessment of inter-session detection of tissue changes: a proof of concept.

PURPOSE: Abnormalities in the bladder wall require careful investigation regarding type, spatial position and invasiveness. Construction of a 3-D model of the bladder is helpful to ensure adequate coverage of the scanning procedure, quantitative comparison of bladder wall textures between successive sessions and finding back previously discovered abnormalities. METHODS: Videos of both an in vivo bladder and a textured bladder phantom were acquired. Structure-from-motion and bundle adjustment algorithms were used to construct a 3-D point cloud, approximate it by a surface mesh, texture it with the back-projected camera frames and draw the corresponding 2-D atlas. Reconstructions of successive sessions were compared; those of the bladder phantom were co-registered, transformed using 3-D thin plate splines and post-processed to highlight significant changes in texture. RESULTS: The reconstruction algorithms of the presented workflow were able to construct 3-D models and corresponding 2-D atlas of both the in vivo bladder and the bladder phantom. For the in vivo bladder the portion of the reconstructed surface area was 58% and 79% for the pre- and post-operative scan, respectively. For the bladder phantom the full surface was reconstructed and the mean reprojection error was 0.081 mm (range 0-0.79 mm). In inter-session comparison the changes in texture were correctly indicated for all six locations. CONCLUSION: The proposed proof of concept was able to perform 3-D and 2-D reconstruction of an in vivo bladder wall based on a set of monocular images. In a phantom study the computer vision algorithms were also effective in co-registering reconstructions of successive sessions and highlighting texture changes between sessions. These techniques may be useful for detecting, monitoring and revisiting suspicious lesions.

Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men.

BACKGROUND: Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of "unnecessary" prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. METHODS: This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥-2.8. Decision curve analysis (DCA) was performed to assess clinical utility. RESULTS: Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. CONCLUSIONS: SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Argus-T adjustable male sling: A follow-up study on urinary incontinence and patient's satisfaction.

AIMS: The use of Argus-T adjustable sling may be a promising alternative option for the treatment of urinary incontinence after radical prostatectomy, however long-term data is lacking. The aim of this study is to evaluate the long-term results of the Argus-T sling on incontinence rates, patient's quality of life and tape-related complications. METHODS: Patients were eligible if persistent stress incontinence was present ≥12 months after radical prostatectomy. Measurements included 24 h frequency volume micturition list, 24 h pad test, 24 h pad count and quality of life questionnaires. Argus-T adjustable sling was placed with a single perineal route incision approach. RESULTS: Seventy-eight patients were included, 69 ± 6 years, pre-intervention 24 h urinary loss 212 (75-385) g. Directly after surgery, 63.6% of the patients was completely dry, 79.2% of the patients reported greater than 90% improvement of their urinary loss and 92.2% > 50% improvement. Median follow-up time was 3.2 (2.5-6.1) years. After 5 years of follow-up, 53.3% of the patients were completely dry, 71.5% reported an improvement greater than 90% and 79.6% reported an improvement of greater than 50%. Patients with preoperative urinary loss less than 250 g reported significantly higher improvement of their urinary loss compared to patients with urinary loss ≥250 g (p = .02). Patients satisfaction was still increased after 5 years follow-up (70 ± 21 vs.16 ± 9, p < .001) and patients quality of life remained high (85 ± 20 vs. 88 ± 13, p = .1). Complications were mainly observed directly after surgery. Two patients (2.6%) needed reimplantation of the sling. CONCLUSION: These data indicate that Argus-T sling is an effective treatment option in obtaining substantial long-term incontinence relief in patients with invalidating moderate stress urinary incontinence after radical prostatectomy.

Optimizing the risk threshold of lymph node involvement for performing extended pelvic lymph node dissection in prostate cancer patients: a cost-effectiveness analysis.

BACKGROUND: Extended pelvic lymph node dissection (ePLND) may be omitted in prostate cancer (CaP) patients with a low predicted risk of lymph node involvement (LNI). The aim of the current study was to quantify the cost-effectiveness of using different risk thresholds for predicted LNI in CaP patients to inform decision making on omitting ePLND. METHODS: Five different thresholds (2%, 5%, 10%, 20%, and 100%) used in practice for performing ePLND were compared using a decision analytic cohort model with the 100% threshold (i.e., no ePLND) as reference. Compared outcomes consisted of quality-adjusted life years (QALYs) and costs. Baseline characteristics for the hypothetical cohort were based on an actual Dutch patient cohort containing 925 patients who underwent ePLND with risks of LNI predicted by the Memorial Sloan Kettering Cancer Center web-calculator. The best strategy was selected based on the incremental cost effectiveness ratio when applying a willingness to pay (WTP) threshold of €20,000 per QALY gained. Probabilistic sensitivity analysis was performed with Monte Carlo simulation to assess the robustness of the results. RESULTS: Costs and health outcomes were lowest (€4,858 and 6.04 QALYs) for the 100% threshold, and highest (€10,939 and 6.21 QALYs) for the 2% threshold, respectively. The incremental cost effectiveness ratio for the 2%, 5%, 10%, and 20% threshold compared with the first threshold above (i.e., 5%, 10%, 20%, and 100%) were €189,222/QALY, €130,689/QALY, €51,920/QALY, and €23,187/QALY respectively. Applying a WTP threshold of €20.000 the probabilities for the 2%, 5%, 10%, 20%, and 100% threshold strategies being cost-effective were 0.0%, 0.3%, 4.9%, 30.3%, and 64.5% respectively. CONCLUSION: Applying a WTP threshold of €20.000, completely omitting ePLND in CaP patients is cost-effective compared to other risk-based strategies. However, applying a 20% threshold for probable LNI to the Briganti 2012 nomogram or the Memorial Sloan Kettering Cancer Center web-calculator, may be a feasible alternative, in particular when higher WTP values are considered.

The Usefulness of the Modified Frailty Index for Muscle-Invasive Bladder Cancer Patients Treated with Radical Cystectomy.

BACKGROUND: Radical cystectomy is still the gold standard for muscle-invasive bladder carcinoma (MIBC) treatment. In order to reduce postoperative complications, multimodality bladder-sparing therapies could be a good alternative. Studies in various malignancies have shown that the modified Frailty Index (mFI) may be more useful for identifying high-risk patients. OBJECTIVES: We investigated the possible correlation between the mFI in cystectomy patients with MIBC and serious complications 30 and 90 days postoperatively. METHODS: Analysis of a prospective database of 109 consecutive MIBC patients who underwent a cystectomy between January 2012 and August 2017 was performed. The mFI was added retrospectively. Differences between groups were tested with independent t-tests, Mann-Whitney U tests, ANOVA, Kruskal-Wallis test, or Chi square tests as appropriate. Univariate and multivariate logistic regression analysis were performed to analyse the relation between the mFI and complications. RESULTS: Patients with Clavien-Dindo ≥ 3 at 30 and 90 days postoperatively had a significantly higher mFI compared to patients with Clavien-Dindo < 3: the odds ratio of the mFI for serious complications within 30 days was 1.5 (95% confidence interval 1.1-2.1, p = 0.010) and for 90 days was 1.5 (95% confidence interval 1.1-2.1, p = 0.008). CONCLUSIONS: We found an association between a high mFI and postoperative complications and mortality. The mFI is therefore useful when discussing treatment options with MIBC patients.

Development and usability testing of a multi-criteria value clarification methods for patients with localized prostate cancer.

Current guidelines for the development of decision aids recommend that they have to include a process for helping patients clarify their personal values, for example, by using values clarification methods. In this article, we extensively described the development process of the web-based values clarification method for patients with localized low- to intermediate-risk prostate cancer based on the analytic hierarchy process. With analytic hierarchy process, the relative importance of different attributes of available treatments can be determined through series of pairwise comparisons of potential outcomes. Furthermore, analytic hierarchy process is able to use this information to present respondents with a quantitative overall treatment score and can therefore give actual treatment advice upon patients' request. The addition of this values clarification method to an existing web-based treatment decision aid for patients with localized prostate cancer is thought to improve the support offered to patients in their decision-making process and their decision quality.

Focal Salvage MR Imaging-Guided Cryoablation for Localized Prostate Cancer Recurrence after Radiotherapy: 12-Month Follow-up.

PURPOSE: To evaluate safety, quality of life (QoL), and local cancer control after focal salvage MR imaging-guided cryoablation in patients with local recurrence of prostate cancer (PCa) after radiotherapy. MATERIALS AND METHODS: A retrospective, single-center study was performed in 62 patients with radiorecurrent PCa who underwent MR imaging-guided cryoablation since May 2011 with a follow-up ≥12 months in December 2017. Rates and descriptions of adverse events were reported. Ablation complications were classified according to the Clavien and SIR systems. Validated questionnaires were used to observe functional outcomes and QoL before therapy and 6 and 12 months after therapy. Cancer control was defined as no biochemical failure according to Phoenix criteria and no other clinical evidence for local or metastatic disease. RESULTS: All procedures were technically feasible. The number of complications requiring major therapy (Clavien grade 3b/4 or SIR grade D/E/F) was low (2 [3.2%] and 1 [1.6%], respectively). After 12 months, the International Consultation of Incontinence Questionnaire-Short Form (P < .001) and 5-item International Index of Erectile Function (P = .001) scores became significantly worse, indicating increased symptoms of incontinence and diminished erectile function, without compromising QoL. Six patients developed metastases within 6 months. After 12 months, 36 patients (63%) were disease-free. CONCLUSIONS: Focal salvage MR imaging-guided cryoablation is safe and is associated with a high technical success rate, preservation of QoL, and local PCa control. This treatment can be a reasonable alternative to salvage radical prostatectomy in properly selected patients with low morbidity and preservation of QoL; however, longer follow-up is needed.

Injectable Bulking Agent to Treat Postprostatectomy Urinary Incontinence: A Safety and Effectiveness Pilot Study.

OBJECTIVES: To evaluate the safety and effectiveness of the injectable bulking agent Opsys® (Promedon, Cordoba, Argentina) for treating minimal postprostatectomy stress urinary incontinence (SUI). PATIENTS AND METHODS: Single-centre, pilot study on ten male patients with SUI, < 30 g urine loss/ 24 h, more than 1 year after radical prostatectomy. Patients were treated by endoscopic transurethral injections of bulking agent in the presphincteric zone of the urethral submucosa. The results were evaluated using a pad weight test to quantify the differences in urine loss at 1, 3, and 6 months after intervention. Subsequently, the results of treatment were also evaluated by International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory Short Form (UDI-6-SF), and the Patient Global Impression of Improvement (PGI-I) at 1, 3, and 6 months after intervention. RESULTS: The primary outcome was the absolute result of the 24-hour pad weight test after treatment. Treatment success was defined as <3 g urine loss/24 h, improvement as ≥50% decrease in urine loss/ 24h, failure as <50% decrease in urine loss/24 h, or worsening of urine loss. Success was demonstrated in one, improvement in one, and failure in eight patients one month after treatment. One patient improved and 9 failed 3 and 6 months after treatment. The median 24-hour pad weight test was higher at all three moments of follow-up (1, 3, and 6 months after treatment). The median 24-hour pad weight test was before treatment 17.3g (6.4-20.9) and 1, 3, and 6 months after treatment, respectively, 40.3g (5.9-130.6) p= 0.038, 38.3g (18.3-202.1) p= 0.014, 55.0g (16.5-314.6) p= 0.028. The ICIQ-SF was significantly higher at 3 and 6 months, respectively 15.0 (12.0-18.5) p= 0.007 and 16.0 (12.5-17.5) p=0.012 versus 10.0 (9.0-12.0) before injection. No significant differences were found between IIQ-7, UDI-6-SF, and PGI-I before and after injection. Complications occurred in four patients: two patients reported spontaneously resolved haematuria and two patients reported urinary frequency. All complications were classified as Clavien-Dindo 1. CONCLUSION: Injection therapy with Opsys® bulking agent is not an effective treatment option for male SUI after radical prostatectomy. It is not a safe treatment option, due to worsening urine loss after treatment.

The impact of prostate cancer diagnosis and treatment decision-making on health-related quality of life before treatment onset.

OBJECTIVE: The objective of this study is to test if patients' health-related quality of life (HRQoL) declines after prostate biopsy to detect Pca, and after subsequent treatment decision-making in case Pca is confirmed, and to test whether personality state and traits are associated with these potential changes in HRQoL. METHODS: Patients who were scheduled for prostate biopsy to detect Pca (N = 377) filled out a baseline questionnaire about HRQoL (EORTC QLQ-C30 and PR25), "big five" personality traits (BFI-10), optimism (LOT-r), and self-efficacy (Decision Self-efficacy Scale) (t0). Patients with confirmed Pca (N = 126) filled out a follow-up questionnaire on HRQoL within 2 weeks after treatment was chosen but had not yet started (t1). RESULTS: HRQoL declined between t0 and t1, reflected in impaired role and cognitive functioning, and elevated fatigue, constipation, and prostate-specific symptoms. Sexual activity and functioning improved. Baseline HRQoL scores were unrelated to the selection of a particular treatment, but for patients who chose a curative treatment, post-decision HRQoL showed a greater decline compared to patients who chose active surveillance. Optimism was associated with HRQoL at baseline; decisional self-efficacy was positively associated with HRQoL at follow-up. No associations between HRQoL and the "big five" personality traits were found. CONCLUSION: Patients who have undergone prostate biopsy and treatment decision-making for Pca experience a decline in HRQoL. Choosing treatment with a curative intent was associated with greater decline in HRQoL. Interventions aimed at optimism and decision self-efficacy could be helpful to reduce HRQoL impairment around the time of prostate biopsy and treatment decision-making.

Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial.

BACKGROUND: The highly frequent strategy of surveillance for non-muscle-invasive bladder cancer (NMIBC) involves cystoscopy and cytology. Urine assays currently available have not shown performance sufficient to replace the current gold standard for follow-up, which would require a very high negative predictive value (NPV), especially for high-grade tumors. Bladder EpiCheck (BE) is a novel urine assay that uses 15 proprietary DNA methylation biomarkers to assess the presence of bladder cancer. OBJECTIVE: To assess the performance of BE for NMIBC recurrence. DESIGN, SETTING, AND PARTICIPANTS: This was a blinded, single-arm, prospective multicenter study. The inclusion criteria were age ≥22 yr, urothelial carcinoma (UC) being monitored cystoscopically at 3-mo intervals, all UC resected within 12 mo, able to produce 10ml of urine, and able to consent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The BE test characteristics were calculated and compared to cytology and cystoscopy results confirmed by pathology. RESULTS AND LIMITATIONS: Out of 440 patients recruited, 353 were eligible for the performance analysis. Overall sensitivity, specificity, NPV, and positive predictive value were 68.2%, 88.0%, 95.1%, and 44.8%, respectively. Excluding low-grade (LG) Ta recurrences, the sensitivity was 91.7% and NPV was 99.3%. The area under receiver operating characteristic (ROC) curves with and without LG Ta lesions was 0.82 and 0.94, respectively. CONCLUSIONS: In follow-up of NMIBC patients, the BE test showed an overall high NPV of 95.1%, and 99.3% when excluding LG Ta recurrences. With high specificity of 88.0%, the test could be incorporated in NMIBC follow-up since high-grade recurrences would be instantly detected with high confidence. Thus, the current burden of repeat cystoscopies and cytology tests could be reduced. PATIENT SUMMARY: The Bladder EpiCheck urine test has a clinically relevant and high negative predictive value. Its use in clinical routine could reduce the number of follow-up cystoscopies, and thus associated patient and financial burdens.

External Validation of Models Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients.

BACKGROUND: Multiple statistical models predicting lymph node involvement (LNI) in prostate cancer (PCa) exist to support clinical decision-making regarding extended pelvic lymph node dissection (ePLND). OBJECTIVE: To validate models predicting LNI in Dutch PCa patients. DESIGN, SETTING, AND PARTICIPANTS: Sixteen prediction models were validated using a patient cohort of 1001 men who underwent ePLND. Patient characteristics included serum prostate specific antigen (PSA), cT stage, primary and secondary Gleason scores, number of biopsy cores taken, and number of positive biopsy cores. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Calibration plots were used to visualize over- or underestimation by the models. RESULTS AND LIMITATIONS: LNI was identified in 276 patients (28%). Patients with LNI had higher PSA, higher primary Gleason pattern, higher Gleason score, higher number of nodes harvested, higher number of positive biopsy cores, and higher cT stage compared to patients without LNI. Predictions generated by the 2012 Briganti nomogram (AUC 0.76) and the Memorial Sloan Kettering Cancer Center (MSKCC) web calculator (AUC 0.75) were the most accurate. Calibration had a decisive role in selecting the most accurate models because of overlapping confidence intervals for the AUCs. Underestimation of LNI probability in patients had a predicted probability of <20%. The omission of model updating was a limitation of the study. CONCLUSIONS: Models predicting LNI in PCa patients were externally validated in a Dutch patient cohort. The 2012 Briganti and MSKCC nomograms were identified as the most accurate prediction models available. PATIENT SUMMARY: In this report we looked at how well models were able to predict the risk of prostate cancer spreading to the pelvic lymph nodes. We found that two models performed similarly in predicting the most accurate probabilities.

Clinical Outcomes and Testosterone Levels Following Continuous Androgen Deprivation in Patients with Relapsing or Locally Advanced Prostate Cancer: A Post Hoc Analysis of the ICELAND Study.

PURPOSE: Lower serum testosterone levels correlate with improved cause specific survival and longer time to progression in year 1 of continuous androgen deprivation in men with prostate cancer. ICELAND was a large European study demonstrating the efficacy of leuprorelin (Eligard®) during continuous androgen deprivation. In this post hoc analysis we investigated serum testosterone levels within year 1 of continuous androgen deprivation to determine survival and time to progression. MATERIALS AND METHODS: In ICELAND (ClinicalTrials.gov NCT00378690) patients with locally advanced or relapsing nonmetastatic prostate cancer and with prostate specific antigen 1 ng/ml or less following 6-month induction with leuprorelin 3-month depot 22.5 mg (plus bicalutamide 50 mg per day for 1 month) were randomized 1:1 to continuous androgen deprivation (361) or intermittent androgen deprivation (340) with leuprorelin for 36 months. Patients receiving continuous androgen deprivation were stratified by minimum, median and maximum testosterone levels during year 1 of therapy into 20 or less, greater than 20 to 50 and greater than 50 ng/dl subgroups. Cause specific survival and time to prostate specific antigen (castrate resistant prostate cancer) progression were analyzed. RESULTS: A total of 90.1%, 83.5% and 74.5% of patients receiving continuous androgen deprivation achieved minimum, median and maximum serum testosterone levels of 20 ng/dl or less, respectively. Cause specific survival rates and time to prostate specific antigen progression did not differ among the testosterone subgroups. CONCLUSIONS: In patients receiving continuous androgen deprivation cause specific survival and time to prostate specific antigen progression did not differ according to testosterone levels in year 1 of therapy. This finding may in part be due to the induction period and the effectiveness of leuprorelin in lowering testosterone.

The effect of office based flexible and rigid cystoscopy on pain experience in female patients.

PURPOSE: Rigid and flexible cystoscopies are both routinely used in female patients. Literature is conflicting whether flexible cystoscopy is less painful compared to rigid cystoscopy. The aim of this study was therefore to investigate whether using flexible cystoscopy leads to less discomfort and pain compared to rigid cystoscopy in female patients who underwent first time cystoscopy. MATERIALS AND METHODS: One hundred eighty-nine female patients, who never had undergone cystoscopy, were randomized into 2 groups: 92 patients underwent rigid cystoscopy and 97 patients flexible cystoscopy. Directly after the cystoscopy procedure all patients were asked to fill out their pain experience on a 100-mm visual analogue pain scale (VAS). RESULTS: Median VAS score was significantly lower for women undergoing flexible cystoscopy (0 [0-20]) compared to rigid cystoscopy (15 [0-38], p<0.001). In addition, age was inversely associated with VAS score, indicating that younger females experienced more pain (R=-0.30, p=0.001). The use of flexible cystoscopy was associated with a decrease in VAS score and remained significant after adjustment for age, sex of urologist, performing urologist and indication (standardized ß=-0.17, p=0.048). CONCLUSIONS: The use of flexible cystoscopy resulted in a significantly lower pain experience compared to rigid cystoscopy. Based on patient's pain experience during cystoscopy, this study implicates to use flexible cystoscopy in female patients who undergo first time cystoscopy.

MRI-guided focal laser ablation for prostate cancer followed by radical prostatectomy: correlation of treatment effects with imaging.

PURPOSE: To correlate treatment effects of MRI-guided focal laser ablation in patients with prostate cancer with imaging using prostatectomy as standard of reference. METHODS: This phase I study was approved by the Institutional Review Board. Three weeks prior to prostatectomy, five patients with histopathologically proven, low/intermediate grade prostate cancer underwent transrectal MRI-guided focal laser ablation. Per patient, only one ablation was performed to investigate the effect of ablation on the tissue rather than the effectiveness of ablation. Ablation was continuously monitored with real-time MR temperature mapping, and damage-estimation maps were computed. A post-ablation high-resolution T1-weighted contrast-enhanced sequence was acquired. Ablation volumes were contoured and measured on histopathology specimens (with a shrinkage factor of 1.15), T1-weighted contrast-enhanced images, and damage-estimation maps, and were compared. RESULTS: A significant volume correlation was seen between the ablation zone on T1-weighted contrast-enhanced images and the whole-mount histopathology section (r = 0.94, p = 0.018). The damage-estimation maps and histopathology specimen showed a correlation of r = 0.33 (p = 0.583). On histopathology, the homogeneous necrotic area was surrounded by a reactive transition zone (1-5 mm) zone, showing neovascularisation, and an increased mitotic index, indicating increased tumor activity. CONCLUSIONS: The actual ablation zone was better indicated by T1-weighted contrast-enhanced than by damage-estimation maps. Histopathology results highlight the importance of complete tumor ablation with a safety margin.

MR-targeted TRUS prostate biopsy using local reference augmentation: initial experience.

PURPOSE: To evaluate MR-targeted TRUS prostate biopsy using a novel local reference augmentation method. PATIENTS AND METHODS: Tracker-based MR-TRUS fusion was applied using local reference augmentation. In contrast to conventional whole gland fusion, local reference augmentation focuses the highest registration accuracy to the region surrounding the lesion to be biopsied. Pre-acquired multi-parametric MR images (mpMRI) were evaluated using PIRADS classification. T2-weighted MR images were imported on an ultrasound machine to allow for MR-TRUS fusion. Biopsies were targeted to the most suspicious lesion area identified on mpMRI. Each target was biopsied 1-5 times. For each biopsied lesion the diameter, PIRADS and Gleason scores, visibility during fusion, and representativeness were recorded. RESULTS: Included were 23 consecutive patients with 25 MR suspicious lesions, of which 11 patients had a previous negative TRUS-guided biopsy and 12 were biopsy naïve. The cancer detection rate was 64 % (Gleason score ≥6). Biopsy was negative (i.e., no Gleason score) in seven patients confirmed by follow-up in all of them (up to 18 months). After MR-TRUS fusion, 88 % of the lesions could be visualized on TRUS. The cancer detection rate increases with increasing lesion size, being 73 % for lesions larger than 10 mm. CONCLUSION: Tracker-based MR-TRUS fusion biopsy with local reference augmentation is feasible, especially for lesions with an MR maximum diameter of at least 10 mm or PIRADS 5 lesions. If this is not the case, we recommend in-bore MR-guided biopsy.

Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score.

BACKGROUND: To reduce overdiagnosis and overtreatment, a test is urgently needed to detect clinically significant prostate cancer (PCa). OBJECTIVE: To develop a multimodal model, incorporating previously identified messenger RNA (mRNA) biomarkers and traditional risk factors that could be used to identify patients with high-grade PCa (Gleason score ≥7) on prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: In two prospective multicenter studies, urine was collected for mRNA profiling after digital rectal examination (DRE) and prior to prostate biopsy. The multimodal risk score was developed on a first cohort (n=519) and subsequently validated clinically in an independent cohort (n=386). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The mRNA levels were measured using reverse transcription quantitative polymerase chain reaction. Logistic regression was used to model patient risk and combine risk factors. Models were compared using the area under the curve (AUC) of the receiver operating characteristic, and clinical utility was evaluated with a decision curve analysis (DCA). RESULTS AND LIMITATIONS: HOXC6 and DLX1 mRNA levels were shown to be good predictors for the detection of high-grade PCa. The multimodal approach reached an overall AUC of 0.90 (95% confidence interval [CI], 0.85-0.95) in the validation cohort (AUC 0.86 in the training cohort), with the mRNA signature, prostate-specific antigen (PSA) density, and previous cancer-negative prostate biopsies as the strongest, most significant components, in addition to nonsignificant model contributions of PSA, age, and family history. For another model, which included DRE as an additional risk factor, an AUC of 0.86 (95% CI, 0.80-0.92) was obtained (AUC 0.90 in the training cohort). Both models were successfully validated, with no significant change in AUC in the validation cohort, and DCA indicated a strong net benefit and the best reduction in unnecessary biopsies compared with other clinical decision-making tools, such as the Prostate Cancer Prevention Trial risk calculator and the PCA3 assay. CONCLUSIONS: The risk score based on the mRNA liquid biopsy assay combined with traditional clinical risk factors identified men at risk of harboring high-grade PCa and resulted in a better patient risk stratification compared with current methods in clinical practice. Therefore, the risk score could reduce the number of unnecessary prostate biopsies. PATIENT SUMMARY: This study evaluated a novel urine-based assay that could be used as a noninvasive diagnostic aid for high-grade prostate cancer (PCa). When results of this assay are combined with traditional clinical risk factors, risk stratification for high-grade PCa and biopsy decision making are improved.