Cost-effectiveness analysis of different treatment modalities in BCG-unresponsive NMIBC.

OBJECTIVE: Radical cystectomy (RC) is the standard of care (SOC) in BCG-unresponsive NMIBC and is associated with a significant health-related quality-of-life burden. Recently, promising results have been published on Gemcitabine/Docetaxel, Pembrolizumab, and Hyperthermic Intravesical Chemotherapy (HIVEC) as salvage therapy options trying to increase the rate of bladder preservation. Here, we performed a Cost-Effectiveness-Analysis of those treatment modalities. PATIENTS AND METHODS: We developed a Markov model from a payer's perspective drawing on clinical data of single-arm trials testing intravesical gemcitabine/docetaxel and pembrolizumab in BCG-unresponsive NMIBC, as well as clinical data from patients receiving hyperthermic intravesical chemotherapy HIVEC (n = 29) as intravesical salvage chemotherapy at our uro-oncological centre in Cologne. Costs were simulated utilising a non-commercial diagnosis-related groups grouper, utilities were derived from comparable cost-effectiveness studies. We used a Monte Carlo simulation to identify the optimal treatment, comparing the incremental cost effectiveness ratios (ICERs) at a willingness-to-pay threshold of €50 000 (euro)/quality-adjusted life year (QALY). RESULTS: Over a horizon of 10 years, gemcitabine/docetaxel, HIVEC, and pembrolizumab were associated with costs of €48 353, €64 438, and €204 580, as well as a gain of QALYs of 6.16, 6.48, and 6.00, resulting in an ICER of €26 482, €42 567, and €184 533 respectively, in comparison to RC with total costs of €21 871 and a gain of QALYs of 5.01. Monte Carlo simulation identified HIVEC as the treatment of choice under assumption of a WTP of <€50 000. CONCLUSION: Considering a WTP of <€50 000/QALY, gemcitabine/docetaxel and HIVEC are highly cost-effective therapeutic options in BCG-refractory NMIBC, while RC remains the cheapest option. At its current price, pembrolizumab would only be cost-effective assuming a price reduction of at least 70%.

Trophoblast cell surface antigen-2: a promising new biomarker and potential therapeutic target in penile squamous cell carcinoma.

OBJECTIVE: To evaluate the potential utility of antibody-drug conjugates targeting trophoblast cell surface antigen-2 (TROP-2) in patients with primary penile squamous cell carcinoma (PSCC), patients with recurrence (REC cohort), and patient-matched distant metastases (MET cohort), and to assess the potential use of TROP-2 as a predictive non-invasive biomarker in PSCC. METHODS: A cohort comprising a PRIM (n = 37), REC (n = 5) and MET subcohort (n = 7), with MET including lymph node and lung metastases, was analysed using quantitative real-time PCR, ELISA and immunohistochemical staining with evaluation of H-score. RESULTS: TROP-2 mRNA and serum protein levels were significantly increased in primary and recurrent PSCC compared to cancer-free controls (both P < 0.001). Immunohistochemical analysis revealed that most of the PRIM cohort (n = 34/37, median H-score 260, interquartile range [IQR] 210-300), as well as all patients in the REC (median [IQR] H-score 200 [165-290]) and MET cohorts (median [IQR] H-score 280 [260-300]) exhibited moderate to strong membranous TROP-2 expression. Additionally, The H-score (membranous TROP-2 expression) was positively correlated with TROP-2 mRNA (ρ = 0.69, P < 0.0001, R2 = 0.70) and protein levels (ρ = 0.86, P < 0.0001, R2 = 0.59), indicating its potential as a non-invasive biomarker in PSCC. CONCLUSION: In summary, our results support further studies on TROP-2 as a diagnostic and therapeutic target in primary, recurrent and metastatic PSCC.

Systemic Radioligand Therapy with (177)Lu Labeled Prostate Specific Membrane Antigen Ligand for Imaging and Therapy in Patients with Metastatic Castration Resistant Prostate Cancer.

PURPOSE: We report our initial clinical experience with ß -emitting (177)Lu-PSMA-I&T ((177)Lu labeled prostate specific membrane antigen ligand for imaging and therapy) for systemic treatment of metastatic castration resistant prostate cancer. MATERIALS AND METHODS: Patients with metastatic castration resistant prostate cancer who experienced treatment failure with chemotherapy and novel androgen receptor targeted therapy were treated for 8 weeks with up to 4 cycles of (177)Lu-PSMA-I&T. We report safety data, the antitumor response with prostate specific antigen decreases and the radiographic tumor response as well as the clinical outcome with changes in ECOG (Eastern Cooperative Oncology Group) performance status and pain severity. RESULTS: The first 3 patients were treated with a lower activity of 3.7 GBq in cycle 1. Due to a favorable safety profile the activity was increased to 7.4 GBq in 19 subsequent patients who completed a total of 40 cycles. With the higher activity no grade 3/4 toxicities were observed. The main nonhematological and hematological grade 1/2 toxicities were dry mouth in 7 patients (37%), anemia in 6 (32%) and thrombopenia in 5 (25%). The proportion of patients who achieved a maximum prostate specific antigen decrease of 30% or greater, 50% or greater and 90% or greater was 56%, 33% and 11%, respectively. Combined assessment of bone and soft tissue metastases showed complete remission in 5% of patients, stable disease in 63% and progressive disease in 32%. ECOG performance status improved or was stable in 74% of patients. Of men with bone pain 58% achieved complete resolution or reduced pain. CONCLUSIONS: Radioligand therapy with (177)Lu-PSMA-I&T appears to be safe and active in heavily pretreated patients with metastatic castration resistant prostate cancer.

Photodynamic Inactivation of Actinomyces naeslundii in Comparison With Chlorhexidine and Polyhexanide--A New Approach for Antiseptic Treatment of Medication-Related Osteonecrosis of the Jaw?

PURPOSE: Local antimicrobial therapy is a fundamental principle in the treatment of lesions of medication-related osteonecrosis of the jaw. Antimicrobial photodynamic therapy (aPDT) as a local application for the treatment of microbial infections has become more widely used in recent years. In the mouth, the bone surface is in constant contact with saliva and thus cannot be kept sterile, making the development of strategies for disinfection even more important. Different methods currently in use include local rinses with chlorhexidine (CHX), polyhexanide (PHX), or aPDT. This study compared the efficiency of these 3 methods. MATERIALS AND METHODS: The in vitro activity of 3 different agents against slowly growing Actinomyces naeslundii isolated from a patient with osteonecrosis was evaluated. PHX 0.04% solution, CHX 0.12% solution, and methylene blue (MB) based dye with a laser light of 660-nm wavelength (aPDT) were compared. RESULTS: The decrease in colony-forming units by each method was measured using an in vitro killing assay based on a water-exposed surface in a well plate. MB dye with laser (10 seconds) decreased the bacterial load by more than 4 orders of magnitude and was superior to PHX and CHX exposure for 60 seconds. CONCLUSION: Laser exposure alone and MB dye exposure alone decreased bacterial loads slightly, but less efficiently than 60-second exposure to PHX or CHX. The most effective means of decreasing colony-forming units was achieved by a combination of laser light and dye, which also can be used clinically.

Efficient quantification and characterization of bacterial outer membrane derived nano-particles with flow cytometric analysis.

There currently exists no efficient and easy method for size profiling and counting of membranous nano-scale particles, such as bacterial outer membrane vesicles (OMVs). We present here a cost-effective and fast method capable of profiling and counting small sample volumes of nano-scale membranous vesicles with standard laboratory equipment without the need for any washing steps. OMV populations of different bacterial species are compared and even subpopulations of OMVs can be identified after a simple labelling procedure. Counting is possible over three orders of magnitude without any changes to the protocol. Protein contaminations do not alter the described measurements.

HIVEC as an alternative option in non-muscle-invasive bladder cancer: Experiences from a high-volume center.

BACKGROUND: High risk non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical BCG-therapy. In case of BCG failure radical cystectomy (RC) is the treatment of choice. Nevertheless, many patients are unfit for or unwilling to undergo RC. Hyperthermic intravesical chemotherapy (HIVEC) is a promising bladder sparing therapy in such cases. It was the purpose of the study to evaluate the efficacy of HIVEC in patients with BCG failure as well as in BCG naïve patients in case of BCG shortage or given contra-indications for BCG. METHODS: We analyzed the first 60 patients who received hyperthermic intravesical chemotherapy (HIVEC) at our department. The therapy regimen consisted of an induction course of 6 weekly sessions, followed by a maintenance course with 6 monthly sessions. Fluorescence cystoscopy with urine cytology and bladder mapping was performed after completion of induction and maintenance therapy at 3 and 12 months. About 68.6 % had received a recurrence after or during BCG treatment, 55% of the subjects were BCG-unresponsive NMIBC according to EAU guidelines. RESULTS: The median follow up was 12 months with 12 cycles of HIVEC therapy being administered on average, representing completion of induction and maintenance therapy with 6 cycles each. The 1- and 2-year recurrence-free-survival (RFS) was 67% and 40% respectively. Only one out of 60 patients developed progression to muscle invasion with progression-free-survival (PFS) of 98% at 2 years. No statistical differences were found in RFS for patients failure to BCG compared to patients that were BCG-naïve (BCG unresponsive vs. BCG-naïve) and patients that carried carcinoma in situ (CIS) compared to patients without CIS (CIS vs. no CIS). CONCLUSION: Chemohyperthermia using HIVEC results in high recurrence-free survival and a 2-year progression-free survival rate of 98% with a bladder preservation rate of almost 80%. Comparing our data, HIVEC shows better oncological results together with better tolerability and safety making HIVEC a good alternative for patients who refuse radical cystectomy or who are ineligible for radical cystectomy.

Deep-Learning-Based Image Denoising in Imaging of Urolithiasis: Assessment of Image Quality and Comparison to State-of-the-Art Iterative Reconstructions.

This study aimed to compare the image quality and diagnostic accuracy of deep-learning-based image denoising reconstructions (DLIDs) to established iterative reconstructed algorithms in low-dose computed tomography (LDCT) of patients with suspected urolithiasis. LDCTs (CTDIvol, 2 mGy) of 76 patients (age: 40.3 ± 5.2 years, M/W: 51/25) with suspected urolithiasis were retrospectively included. Filtered-back projection (FBP), hybrid iterative and model-based iterative reconstruction (HIR/MBIR, respectively) were reconstructed. FBP images were processed using a Food and Drug Administration (FDA)-approved DLID. ROIs were placed in renal parenchyma, fat, muscle and urinary bladder. Signal- and contrast-to-noise ratios (SNR/CNR, respectively) were calculated. Two radiologists evaluated image quality on five-point Likert scales and urinary stones. The results showed a progressive decrease in image noise from FBP, HIR and DLID to MBIR with significant differences between each method (p < 0.05). SNR and CNR were comparable between MBIR and DLID, while it was significantly lower in HIR followed by FBP (e.g., SNR: 1.5 ± 0.3; 1.4 ± 0.4; 1.0 ± 0.3; 0.7 ± 0.2, p < 0.05). Subjective analysis confirmed best image quality in MBIR, followed by DLID and HIR, both being superior to FBP (p < 0.05). Diagnostic accuracy for urinary stone detection was best using MBIR (0.94), lowest using FBP (0.84) and comparable between DLID (0.90) and HIR (0.90). Stone size measurements were consistent between all reconstructions and showed excellent correlation (r2 = 0.958-0.975). In conclusion, MBIR yielded the highest image quality and diagnostic accuracy, with DLID producing better results than HIR and FBP in image quality and matching HIR in diagnostic precision.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis.

OBJECTIVES: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). METHODS: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. RESULTS: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). CONCLUSIONS: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Multimodal image-guided prostate fusion biopsy based on automatic deformable registration.

PURPOSE: Transrectal ultrasound (TRUS)-guided random prostate biopsy is, in spite of its low sensitivity, the gold standard for the diagnosis of prostate cancer. The recent advent of PET imaging using a novel dedicated radiotracer, [Formula: see text]-labeled prostate-specific membrane antigen (PSMA), combined with MRI provides improved pre-interventional identification of suspicious areas. This work proposes a multimodal fusion image-guided biopsy framework that combines PET-MRI images with TRUS, using automatic segmentation and registration, and offering real-time guidance. METHODS: The prostate TRUS images are automatically segmented with a Hough transform-based random forest approach. The registration is based on the Coherent Point Drift algorithm to align surfaces elastically and to propagate the deformation field calculated from thin-plate splines to the whole gland. RESULTS: The method, which has minimal requirements and temporal overhead in the existing clinical workflow, is evaluated in terms of surface distance and landmark registration error with respect to the clinical ground truth. Evaluations on agar-gelatin phantoms and clinical data of 13 patients confirm the validity of this approach. CONCLUSION: The system is able to successfully map suspicious regions from PET/MRI to the interventional TRUS image.