Outcomes of a Diagnostic Pathway for Prostate Cancer Based on Biparametric MRI and MRI-Targeted Biopsy Only in a Large Teaching Hospital.

BACKGROUND: Diagnostic pathways for prostate cancer (PCa) balance detection rates and burden. MRI impacts biopsy indication and strategy. METHODS: A prospectively collected cohort database (N = 496) of men referred for elevated PSA and/or abnormal DRE was analyzed. All underwent biparametric MRI (3 Tesla scanner) and ERSPC prostate risk-calculator. Indication for biopsy was PIRADS ≥ 3 or risk-calculator ≥ 20%. Both targeted (cognitive-fusion) and systematic cores were combined. A hypothetical full-MRI-based pathway was retrospectively studied, omitting systematic biopsies in: (1) PIRADS 1-2 but risk-calculator ≥ 20%, (2) PIRADS ≥ 3, receiving targeted biopsy-cores only. RESULTS: Significant PCa (GG ≥ 2) was detected in 120 (24%) men. Omission of systematic cores in cases with PIRADS 1-2 but risk-calculator ≥ 20%, would result in 34% less biopsy indication, not-detecting 7% significant tumors. Omission of systematic cores in PIRADS ≥ 3, only performing targeted biopsies, would result in a decrease of 75% cores per procedure, not detecting 9% significant tumors. Diagnosis of insignificant PCa dropped by 52%. PCa undetected by targeted cores only, were ipsilateral to MRI-index lesions in 67%. CONCLUSIONS: A biparametric MRI-guided PCa diagnostic pathway would have missed one out of six cases with significant PCa, but would have considerably reduced the number of biopsy procedures, cores, and insignificant PCa. Further refinement or follow-up may identify initially undetected cases. Center-specific data on the performance of the diagnostic pathway is required.

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

PURPOSE: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. METHODS: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). RESULTS: Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674). CONCLUSION: There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.

Feasibility of clinical studies of chemical exchange saturation transfer magnetic resonance imaging of prostate cancer at 7 T.

Chemical exchange saturation transfer (CEST) has been explored for differentiation between tumour and benign tissue in prostate cancer (PCa) patients. With ultrahigh field strengths such as 7-T, the increase of spectral resolution and sensitivity could allow for selective detection of amide proton transfer (APT) at 3.5 ppm and a group of compounds that resonate at 2 ppm (i.e., [poly]amines and/or creatine). The potential of 7-T multipool CEST analysis of the prostate and the detection of PCa was studied in patients with proven localised PCa who were scheduled to undergo robot-assisted radical prostatectomy (RARP). Twelve patients were prospectively included (mean age 68.0 years, mean serum prostate-specific antigen 7.8ng/mL). A total of 24 lesions larger than 2 mm were analysed. Used were 7-T T2-weighted (T2W) imaging and 48 spectral CEST points. Patients received 1.5-T/3-T prostate magnetic resonance imaging and galium-68-prostate-specific membrane antigen-positron emission tomography/computerised tomography to determine the location of the single-slice CEST. Based on the histopathological results after RARP, three regions of interest were drawn on the T2W images from a known malignant zone and benign zone in the central and peripheral zones. These areas were transposed to the CEST data, from which the APT and 2-ppm CEST were calculated. The statistical significance of the CEST between the central zone, the peripheral zone, and tumour was calculated using a Kruskal-Wallis test. The z-spectra showed that APT and even a distinct pool that resonated at 2 ppm were detectable. This study showed a difference trend in the APT levels, but no difference in the 2-ppm levels when tested between the central zone, the peripheral zone, and tumour (H(2) = 4.8, p = 0.093 and H(2) = 0.86, p = 0.651, respectively). Thus, to conclude, we could most likely detect APT and amines and/or creatine levels noninvasively in prostate using the CEST effect. At group level, CEST showed a higher level of APT in the peripheral versus the central zone; however, no differences of APT and 2-ppm levels were observed in tumours.

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Detect Residual Prostate Cancer Following Irreversible Electroporation-A Multicenter Validation Study.

BACKGROUND: Accurate monitoring following focal treatment of prostate cancer (PCa) is paramount for timely salvage treatment or retreatment. OBJECTIVE: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) to detect residual PCa in the short-term follow-up of focal treatment with irreversible electroporation (IRE) using transperineal or transrectal template ± targeted biopsies. DESIGN, SETTING, AND PARTICIPANTS: A retrospective international multicenter study of men with biopsy-proven PCa, treated with focal IRE, and followed by mpMRI (index-test) and template biopsies (reference-test) between February 2013 and January 2021, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI were calculated for in- and outfield residual disease based on two definitions of significant PCa: University College London (UCL) 1-International Society of Urological Pathology (ISUP) ≥3 or ISUP ≥1 with maximum cancer core length (MCCL) ≥6 mm, and UCL2-ISUP ≥2 or ISUP ≥1 with MCCL ≥4 mm. RESULTS AND LIMITATIONS: A total of 303 patients from five focal therapy centers were treated with primary IRE. The final analysis was performed on 217 men (median age 67, median prostate-specific antigen 6.2, 81% ISUP 2/3) who underwent both mpMRI and template biopsies. Multiparametric MRI missed 38/57 (67%) positive biopsy locations (UCL1) in 22 patients. Sensitivity, specificity, PPV, and NPV of mpMRI to detect whole gland residual disease (UCL1) were 43.6% (95% confidence interval [CI]: 28-59), 80.9% (95% CI: 75-86), 33.3% (95% CI: 21-47), and 86.7% (95% CI: 81-91), respectively. Based on UCL2, sensitivity, specificity, PPV, and NPV were 35.8% (95% CI: 25-48), 82.0% (95% CI: 75-88), 47.1% (95% CI: 34-61), and 74.1% (95% CI: 67-80), respectively. Limitations are the retrospective nature and short follow-up. CONCLUSIONS: The diagnostic accuracy of mpMRI to detect residual clinically significant PCa following IRE was low. Follow-up template biopsies should be performed, regardless of mpMRI results. PATIENT SUMMARY: We investigated the accuracy of magnetic resonance imaging (MRI) to detect residual prostate cancer after treatment with irreversible electroporation. The accuracy of MRI is insufficient, and we emphasize the importance of confirmatory prostate biopsies.

Hospital variation in treatment patterns and oncological outcomes for patients with muscle-invasive and metastatic bladder cancer in the Netherlands.

PURPOSE: Population-based studies on treatment patterns in oncology and corresponding clinical outcomes can help identify strategies towards optimal value for patients. This study was performed to describe the variation in treatment patterns and major oncological outcomes for muscle-invasive or metastatic bladder cancer (MIBC/mBC) patients in the Netherlands. METHODS: Patients diagnosed with cT2-4aN0-3M0-1 disease between 2008 and 2016 in seven large teaching hospitals in the Netherlands were included. Baseline characteristics, disease stage, intended and definitive treatment, and oncological outcomes were collected. Patients were categorized based on cTNM-stage: (1) cT2-4aN0M0, (2) cT2-4aN1-3M0 and (3) cT4b and/or M1. RESULTS: The total study population comprised 1853 patients, of which 1303 patients were diagnosed with cT2-4aN0M0 disease. Overall, curative treatment was intended in 81% (range 74-85%, P value = 0.132). Radical cystectomy (RC) and curative radiotherapy (RTx) ranged between hospitals from 42 to 66% and 13 to 27%, respectively (P value < 0.001). For 334 patients staged cT4b and/or M1, frequencies for palliative therapy and best supportive care (no anti-cancer therapy) ranged between hospitals from 20 to 54% and 44 to 71%, respectively (P value < 0.001). There was no association between hospital site and overall survival (OS) in a univariable and multivariable Cox regression for survival analysis (after adjusting for age and cT-stage), for all three cTNM-groups. Neoadjuvant or induction chemotherapy (NAIC) utilization rates before RC ranged from 8 to 38% (P value < 0.001). CONCLUSIONS: There is large inter-hospital variation in treatment intent in MIBC/mBC patients. This variation does not seem to translate to differences in overall survival rates. There is an ongoing trend of increased use of RC. Utilisation of NAIC is relatively low considering European guideline recommendations.

Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer.

OBJECTIVE: To evaluate: (i) safety, (ii) feasibility, and medium-term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE). PATIENTS AND METHODS: An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life. RESULTS: In four participating centres, a total of 39 patients with a median (interquartile range [IQR]) age 64 (60-67) years were identified. No serious adverse events occurred during or following sRP and surgery was deemed feasible without difficulties. The median (IQR) time to recurrence following IRE was 14.3 (9.1-38.8) months. Pathology results showed localised disease in 21 patients (53.8%) and locally-advanced disease in 18 (46.2%). Positive surgical margins (PSMs) were observed in 10 patients (25.6%), of which six (15.4%) had significant PSMs. A persistent detectable prostate-specific antigen level was found in one case after sRP, caused by metastatic disease. One patient had a biochemical recurrence 6 months after sRP. These two cases, together with a PSM case, required additional therapy after sRP. After a median (IQR) follow-up of 17.7 (11.8-26.4) months, urinary continence and erectile function were preserved in 34 (94.4%) and 18 patients (52.9%), respectively, while quality of life remained stable. CONCLUSIONS: Salvage RP is safe and feasible for patients with recurrent localised PCa following initial IRE treatment. The medium-term oncological and functional outcomes are similar to primary RP. Strict patient selection for focal therapy and standardised follow-up is needed as some patients developed high-grade disease.

Development of the First Patient-centred Set of Outcomes for Muscle-invasive and Metastatic Bladder Cancer: A Multicentre Initiative.

BACKGROUND: To improve and compare outcomes in healthcare, it is necessary to standardise outcome measurements. There are no widely accepted standardised outcome measures reflecting quality of care for bladder cancer (BCa) patients. OBJECTIVE: The aim of this study was to create a standardised set of outcomes for patients with muscle-invasive or metastatic BCa, using the value-based healthcare principles. DESIGN SETTING AND PARTICIPANTS: A multidisciplinary working group of 25 healthcare professionals and patient representatives was assembled, to develop the set. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used an online RAND-modified Delphi process to prioritise, discuss, and reach consensus regarding the outcomes, case-mix variables, and treatment factors. RESULTS AND LIMITATIONS: Recognising the heterogeneity of patients with BCa, the working group defined the scope as patients with muscle-invasive and metastatic BCa. A total of 24 outcomes, including ten patient-reported outcomes, were included in the standard set of outcomes, covering survival, complication rates, recurrence of disease, readmissions after treatment, and quality of life (QoL). Fourteen case-mix variables were included. The EQ-5D and European Organisation for Research and Treatment of Cancer quality of life (EORTC-QLQ) questionnaires were recommended to measure QoL. CONCLUSIONS: We developed the first standardised set of patient-centred outcomes for muscle-invasive and metastatic BCa. The sue of this set enables institutions to monitor, compare, and improve the quality of BCa care, on an international level. PATIENT SUMMARY: Our group of healthcare professionals and patient representatives recommended a standardised set of patient-centred outcomes to be followed during the treatment of patients with muscle-invasive or metastatic bladder cancer, in order to monitor, compare, and improve the quality of care.

Comparison of risk-calculator and MRI and consecutive pathways as upfront stratification for prostate biopsy.

PURPOSE: In biopsy naïve men suspected for prostate cancer (PCa), it is uncertain how a risk-calculator and bi-parametric (bp) MRI should be combined to decide on prostate biopsy, balancing cancer detection rates and diagnostic burden. METHODS: Prospective, single centre cohort study (August 2018-April 2019). All patients referred with serum PSA ≥ 3 ng/ml or abnormal digital rectal examination received bpMRI and risk for PCa was calculated using the ERSPC risk-calculator. Men with either PI-RADS ≥ 3 or calculator risk-score > 20% were recommended to undergo systematic biopsy (SB) and targeted biopsy (TB) of any visible lesion (reference pathway). Eight different derived diagnostic pathways were compared to the reference pathway regarding cancer detection, number of biopsies and bpMRIs performed. RESULTS: Of 496 patients; 233 (47%) had a risk-calculator score of > 20%; 201 (41%) had PI-RADS score ≥ 3. The reference pathway detected PCa in 32.1%, clinically significant (cs) PCa in 19.4%, with 41% avoided biopsies, but 0% avoided bpMRI. Stratification with only risk-calculator: 76% csPCa diagnosed, 53% avoided biopsies and 100% avoided bpMRI. Stratification with only bpMRI: 97% csPCa diagnosed, 59% avoided biopsies, but 0% avoided bpMRI. A pathway with risk-calculator first, followed only with bpMRI when high-risk: 81% csPCa diagnosed, 72% avoided biopsies and 53% avoided bpMRI. CONCLUSION: Upfront bpMRI as a risk stratification tool outperforms risk-calculator in detecting significant disease. Applying the risk-calculator first to decide on performing an MRI, avoids 1 out of 2 MRIs, but up to 1 out of 5 significant cancers are missed.

Evaluation of Ureteroenteric Anastomotic Strictures after the Introduction of Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Results from a Large Tertiary Referral Center.

PURPOSE: Benign ureteroenteric anastomotic strictures following radical cystectomy are a critical complication. The incidence is highly dependent on study design, surgical technique and surgeon experience. We studied the incidence of ureteroenteric anastomotic strictures after open vs robot-assisted radical cystectomy with an intracorporeal urinary diversion, and determined the influence of the introduction of robot-assisted radical cystectomy in our clinic. MATERIALS AND METHODS: A retrospective, single center, cohort study was performed between January 2012 and December 2017 in all patients undergoing radical cystectomy. Multivariate analysis was performed to determine which patient or disease-specific factors were associated with development of ureteroenteric anastomotic strictures. RESULTS: Of 279 patients, 192 (69%) underwent open radical cystectomy and 87 (31%) underwent robot-assisted radical cystectomy with intracorporeal urinary diversion. In total, 47/279 patients (17%) developed ureteroenteric anastomotic strictures after a median of 3.0 months (95% CI 2.4-3.7). The difference in incidence of ureteroenteric anastomotic strictures was statistically significant between open and robot-assisted radical cystectomy (13% vs 25%, p <0.001). On multivariate analysis, only surgical technique (open vs robot-assisted radical cystectomy) was independently associated with development of ureteroenteric anastomotic strictures (p=0.004). There was a peak incidence of ureteroenteric anastomotic strictures after robot-assisted radical cystectomy of 47% during the first year after introduction of the robot-assisted procedure. CONCLUSIONS: Introducing robot-assisted radical cystectomy with intracorporeal urinary diversion can result in an initial peak incidence of strictures, highlighting the importance of surgeon experience and the presence of a learning curve. Nonetheless, after experience has been gained, our results show that patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion are still more likely to develop ureteroenteric anastomotic strictures compared to those undergoing open radical cystectomy.

Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands.

This retrospective study was performed to evaluate real-world oncological outcomes of patients treated with chemo-based therapy for muscle-invasive or metastatic bladder cancer (MIBC/mBC) and compare results to data from RCTs and other cohorts. Among 1578 patients diagnosed, 470 (30%) had MIBC/mBC. Median overall survival (mOS) for RC alone (47 months), first-line (13 months) and second-line (7 months) chemotherapy, and chemotherapy for recurrent disease (8 months) were similar to literature. Treatment with neoadjuvant and induction chemotherapy (NAIC) was only utilized in 9% of patients, and often in patients with poor disease status, resulting in a lower mOS compared to literature (35 and 20 months, respectively). Patients treated with chemotherapy had many adversities to treatment, with only 50%, 13%, 18% and 7% of patients in NAIC, first-line, salvage after RC, and second-line setting completing the full pre-planned chemotherapy treatment. Real-world data shows NAIC before RC is underutilized. Adversities during chemotherapy treatment are frequent, with many patients requiring dose reduction or early treatment termination, resulting in poor treatment response. Although treatment efficacy between RCTs and real-world patients is quite similar, there are large differences in baseline characteristics and treatment patterns. Possibly, results from retrospective studies on real-world data can deliver missing evidence on efficacy of chemotherapy treatment on older and 'unfit' patients.

Sneeze and pop: a ruptured varicocele; analysis of literature, guided by a well-documented case-report.

BACKGROUND: An acute scrotal hematoma, secondary to a spontaneous rupture of a varicocele is still a rare presentation in daily practice. However, multiple case reports have been reported. Sudden increase in abdominal pressure, resulting to an increased venous pressure can lead to a rupture of the varicocele. Literature search shows that due to uncertainty of the diagnosis, explorative surgery is often performed, sometimes resulting in unnecessary orchiectomies. The objective of this study was to determine classical clinical presentation of patients with a spontaneous rupture of a varicocele, determine the diagnostic procedure, and give an insight in the follow-up. CASE PRESENTATION: We present a case of a 24-year old male with acute scrotal swelling after sneezing. Subsequently, we carried out a systematic literature search to identify all eligible studies to determine classic clinical presentation of spontaneous ruptures of a varicocele. CONCLUSION: The literature search shows that clinical presentation of idiopathic spontaneous scrotal hematomas is similar to testicular torsion, epididymo-orchitis, malignancy, or (incarcerated) inguinal hernia making differential diagnosis difficult. Especially when there has been increased abdominal pressure or strenuous activity preceding the symptoms, and the swelling is left sided, it should be included in the differential diagnosis for patient with acute inguinoscrotal swelling. Colour Doppler-Ultrasonography is recommended to distinguish between other causes of acute scrotum. The hematoma is usual self-limiting, justifying conservative treatment. Early surgical intervention is indicated with signs of ischaemia due to obstruction, infection of the hematoma, or uncertain diagnosis (i.e. malignancy). However, physicians should be cautious with direct exploration, as it led to unnecessary orchiectomy in 25% of patients. The hematoma can increase in size up to 3 months post-event, and it can take up to 15 months to completely resolve.

Extracorporeal shock wave lithotripsy under intravenous sedation for treatment of urolithiasis.

BACKGROUND: In contrast to treatment with oral or intramuscular analgesics, extracorporeal shock wave lithotripsy (E.S.W.L.) can be performed with patients under sedation too. Besides the advantage of increased shock energy, patients tend to have more constant breathing excursions and are more idle during treatment, potentially increasing the stone-free ratio (S.F.R.) after treatment. METHODS: This study presents the results of 310 patients who underwent 400 E.S.W.L. procedures under sedation, with a stationary lithotripter. RESULTS: After one procedure, the S.F.R. was 54.8% (170/310). A second treatment was successful in 42.1% (32/76), a third treatment in 21.4% (3/14). Therefore, 66.1% (205/310) of patients eventually became stone-free. Kidney stones were successfully treated in 65.4% (161/246), ureteral stones in 68.8% (44/64) of cases. Patients with stones ≤15 mm were successfully treated in 67.4% (194/288), patients with stones >15 mm in 50% (11/22) of cases. Considering each procedure individually, 45.3% (181/400) of procedures were successful after 3 weeks. Extending follow-up to 3 months is important, since 26.7% of stones (24/90) eventually still disappeared, increasing S.F.R. to 51.3% after one procedure. Complications occurred after 5.5% E.S.W.L.-procedures. CONCLUSIONS: E.S.W.L. is a well-tolerated, non-invasive procedure that produces reasonable stone clearance of both upper and lower urinary tract calculi. Performing the procedure whilst patients are intravenously sedated results in an acceptable S.F.R. Strong selection based on unfavourable factors could increase the chance on successful treatment and spare patients a pointless procedure. However, considering E.S.W.L.'s elegant nature, sometimes a more tolerant approach seems justifiable.

Clinical Relevance of Incidental Prostatic Lesions on FDG-Positron Emission Tomography/Computerized Tomography-Should Patients Receive Further Evaluation?

PURPOSE: FDG ((18)F-fluoro-2-deoxy-D-glucose)-PET/CT (positron emission tomography)/(computerized tomography) is a widely used diagnostic tool for whole body imaging. Incidental prostatic uptake is often found on FDG-PET/CT. The objective of this study was to determine the clinical relevance of incidental prostatic uptake on FDG-PET/CT. MATERIALS AND METHODS: We analyzed 108 consecutive male patients with bladder cancer who underwent FDG-PET/CT and subsequently radical cystoprostatectomy between May 2009 and November 2014. PET/CT scans were blindly reviewed by a dedicated nuclear medicine physician for incidental prostatic FDG uptake. If present, the maximum standardized uptake value was determined. Subsequently incidental prostatic uptake was categorized as suspect, indeterminate or nonsuspect for prostate cancer. RESULTS: Incidental prostatic uptake was present in 43 of 108 patients (40%). Of these 43 patients 13 (30%) had occult prostate cancer in cystoprostatectomy specimens. Overall prostate cancer was found in 25 of 108 specimens (23%). If all incidental prostatic uptake was regarded as prostate cancer, the sensitivity and specificity of FDG-PET/CT for prostate cancer detection were 52% and 64%, respectively. Positive and negative predictive values were 30% and 82%, respectively. If only lesions labeled suspect or indeterminate were regarded as prostate cancer, sensitivity, specificity, and positive and negative predictive values were 32%, 76%, 29% and 79%, respectively. Categorizing indeterminate lesions as nonprostate cancer did not improve diagnostic accuracy. Gleason score did not correlate with maximum standardized uptake value or serum prostate specific antigen. CONCLUSIONS: Incidental prostatic uptake on FDG-PET/CT has a low positive predictive value for prostate cancer. An attempt to classify lesions as suspect or nonsuspect did not increase diagnostic accuracy. Based on these results physicians should be cautious about applying invasive diagnostic methods to detect prostate cancer in case of incidental prostatic uptake on FDG-PET/CT.