[Stage-dependent treatment of seminomas]. / Stadienabhängige Therapie des Seminoms.

Germ cell neoplasms of the testis are rare solid tumors predominantly in young men. Seminomas are slightly more frequent than nonseminomatous germ cell tumors. A special feature of seminomas is that they are sensitive to radiation, so that this represents an option in tumor stages with few metastases; however, the guideline recommendation is cautious due to the increased risk of secondary malignancies. In nonmetastasized tumor stages active surveillance is the primary approach to avoid overtreatment of patients. This is also the reason for primary nerve-sparing retroperitoneal lymph node dissection in cases of a low metastasis load. This concept has already been implemented in the American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) guidelines, whereas in the European Association of Urology (EAU) guidelines it is still considered to be an individual approach.

Ureter-ileum-interposition: Combined experience from two high-volume centres.

The current study aimed to evaluate short- and long-term complication rates and functional outcomes in a substantial cohort of patients undergoing ileal ureter interposition at two high-volume medical centres. Materials and methods: A retrospective single-arm analysis was conducted on patients who underwent ureter reconstruction using ileum between 2003 and 2022 at the University Clinic of Cologne and the National Cancer Institute of Ukraine. Data on aetiology, surgical techniques, pre- and postoperative kidney function changes, readmission rates and complication management were collected. Postoperative complications were classified according to Clavien-Dindo, and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Results: Results revealed 107 cases with consistent data. Within 90 days post-surgery, 53% experienced complications, mainly graded as I-II. Grade III complications were seen in 13%, with two cases of grade IV complications leading to extended hospitalisation and patient death. The 90-day mortality rate was 1.8%. Over a mean follow-up of 52 months, clinically significant vesico-renal refluxes occurred in 28%, with only 5.4% leading to persistent urinary tract infection. Antireflux techniques appeared to reduce urine upflow incidence compared with conventional interposition. Anastomosis stricture occurred in 15% of patients, with 63% requiring permanent re-stenting and 37% needing re-anastomosis. Metabolic acidosis was clinically significant in 7.5% of cases. A slight improvement in renal function was observed during the first year post-surgery (average postoperative eGFR = 76 ± 22 ml/min; Mann-Witney U test, p = 0,0198). Affected kidney function improved in 56 (52%), was stable in 41 (38%) and deteriorated in 10 (9.3%). Loss of kidney function on the surgery side was seen in 4 (3.7%) patients and resulted in nephrectomy in 3 (2.8%) cases. Conclusion: Ileal ureter interposition demonstrated a favourable safety profile and functional outcomes. This surgical intervention provides an effective tension-free bypass, irrespective of healthy ureter length.

Multivariate analysis of the parameters affecting the choice of surgical treatment for patients with localized renal cell carcinoma (RCC).

OBJECTIVE: to determine the key factors affecting the surgical treatment selection for patients with localized Renal-Cell Carcinoma (RCC) based on clinical and nephrometry data. MATERIALS AND METHODS: A retrospective cohort study to determine the key factors affecting the surgical treatment on a subset of patients with localized RCC (T1-T2) that underwent surgical treatment at primary investigational center from 2010 to 2017. Primary results were validated on the retrospective dataset of patients treated at high-volume referent center. Validation aimed to test applicability of the predictive model designed during primary analysis. To determine the relationship between the risks of radical or partial nephrectomy, the multivariate predictive modeling method was used. RESULTS: Based on the analysis, for polary and laterally located tumors, the risk of RN was conditioned only by remaining functioning parenchyma volume (RFPV). The average critical value of RFPV for polar lesions was = 58%; for lateral tumors = 67%. For medial location, the risk of RN only depended on the tumor size. Average critical value of the tumor size in the medial location was = 38mm. Based on the ROC curve comparison, there were no statistically significant differences between the predictive models containing 12 and 3 factors (AUCLin_12 and AUCMLP_3; P = 0.12); thus, the reduced amount of the factor indicators from 12 to 3 did not worsen the model predictive qualities. Designed during primary analysis hypothesis was successfully validated in a referent center on the cohort of 300 patients. Predictive model is characterized by high sensitivity (95.2%) and specificity (95.4%) in selecting patients for partial nephrectomy. CONCLUSIONS: For the polar and lateral tumor locations, the functioning parenchymal volumes of over 58 and 67% respectively serve as PN indications. However, for the medial lesions, the primary PN indication is a tumor size less than 38 mm.

Cost-effectiveness Analysis in the New Era of Treatment Strategies in Metastatic Urothelial Carcinoma Based on Checkmate-901 and EV302/Keynote-A39.

BACKGROUND AND OBJECTIVE: Metastatic urothelial carcinoma (mUCa) ranks as the costliest cancer to treat per patient due to frequent interventions and expensive follow-ups. Investigating first-line therapies, combinations such as enfortumab vedotin + pembrolizumab (EV + P) and gemcitabine/cisplatin + nivolumab exhibit significant overall survival benefits compared with the standard treatment (SoC; gemcitabine/cisplatin). Here, we conducted a cost-effectiveness analysis for mUCa. METHODS: We developed a Markov model from a payer perspective, filtering clinical data from the phase 3 Checkmate-901 and EV302/Keynote-A39 trials. Monte Carlo simulation was used to identify the optimal treatment from a socioeconomic perspective in Germany and the USA. Finally, we compared the incremental cost-effectiveness ratio (ICER) of each modality at different willingness-to-pay (WTP) thresholds. KEY FINDINGS AND LIMITATIONS: At a lifetime horizon, SoC, gemcitabine/cisplatin + nivolumab, and EV + P were associated with average costs of €163 424 (USA: $458 006), €206 853 (USA: $597 802), and €401 170 (USA: $1 228 455), and gained quality-adjusted life years (QALYs) of 1.21, 1.71, and 2.31, respectively. The ICERs of the newer strategies were €87 340 (USA: $281 142; gemcitabine/cisplatin + nivolumab) and €216 140 (USA: $700 448; EV + P). At a commonly used WTP threshold of €/$100 000, gemcitabine/cisplatin + nivolumab would be the optimal strategy in Germany, while EV + P would require a price reduction of 46% (USA: 82%) to be cost effective. CONCLUSIONS AND CLINICAL IMPLICATIONS: QALYs nearly double with EV + P compared with the current SoC; yet, current costs may not be justified from a strict socioeconomic perspective. Despite its lower oncological benefit, gemcitabine/cisplatin + nivolumab should be considered for first-line therapy due to favorable cost effectiveness, especially in Europe. Establishing individual risk factors is essential for optimizing therapeutic response and treatment costs in the future. PATIENT SUMMARY: This report presents a cost-effectiveness analysis of emerging treatment options for metastatic urothelial carcinoma. The combination of enfortumab vedotin + pembrolizumab emerged as the most effective treatment; however, it also proved to be the costliest. From a purely socioeconomic standpoint, the combination of gemcitabine/cisplatin and nivolumab represents a cost-effective alternative at least in Germany.

Efficacy of botulinum toxin in the management of refractory de novo overactive bladder symptoms in women after midurethral sling placement: retrospective, single center study.

Introduction: This study aimed o evaluate the efficacy of onabotulinumtoxin A (onaBTX-A) intradetrusor injections in women with refractory de novo overactive bladder (OAB) following midurethral sling (MUS) placement. Material and methods: A retrospective single-center study was conducted. We screened 372 women who underwent MUS surgery between August 2009 and January 2022. 54/372 women diagnosed with pharmacologically refractory de novo OAB following MUS were evaluated using cystoscopy and urodynamics, and after tape erosion and obstructive voiding were excluded, they received onaBTX-A therapy. Outcomes were the reduction of self-reported OAB symptoms and leakage episodes, improvement of validated OAB scores and adverse events of the procedure after a follow-up of 3, 6, and 12 months. Results: Successful results were reported in 81%, 68%, and 43% at 3, 6 and 12 months respectively. Postoperatively, median voiding frequency and median nocturia episodes were significantly improved in 70% and 77% of women, respectively, with a decrease in daily number of voids (-4.1, p = 0.0001) and nocturia episodes (-2.2, p = 0.005). At 3 months, 80% of women reported an >25% reduction in urgency severity and episodes following injection. The median number of pads used was significantly reduced after injection (-2 pads; p = 0.03). Repeat injections of onaBTX-A were performed in 61% of patients after a median of 11 months. Conclusions: Intravesical onaBTX-A injections are clinically effective at 3- and 6-month follow-up for the treatment of refractory de novo OAB after MUS placement. Over 60% of the patients opted for retreatment with onaBTX-A due to a high level of satisfaction.

[Primary retroperitoneal lymph node dissection in testicular germ cell cancer in clinical stage IIA/B-renaissance of an established treatment?] / Die primäre retroperitoneale Lymphadenektomie beim testikulären Keimzelltumor im klinischen Stadium IIA/B ­ Renaissance einer etablierten Therapie?

BACKGROUND: The guideline-recommended treatment of choice for clinical stage IIA/B testicular germ cell tumors is chemotherapy with three cycles of PEB/four cycles of PE or, alternatively, radiation for seminomas. Despite their high curative efficacy, both options are associated with significant long-term toxicities. We evaluated the functional and oncological outcomes of primary retroperitoneal lymph node dissection (RPLND) as a therapeutic alternative. PATIENTS AND METHODS: Between 2018 and 2022, 76 patients (n = 34 seminomas, n = 42 nonseminomas) underwent primary RPLND for marker-negative clinical stage IIA/B testicular germ cell cancer. All patients underwent nerve-sparing RPLND with a unilateral or bilateral template dissection and had a follow-up ≥ 3 months. None of the patients received adjuvant chemotherapy. In 24 patients, the serum concentration of miR371a-3p was evaluated preoperatively. Follow-up was performed according to EAU guidelines. RESULTS: Median age and median follow-up were 30.1 (17-62) years and 29.3 (3-72) months, respectively. Mean operation time, blood loss, and duration of hospitalization were 131 (105-195) min, < 150 ml, and 4.5 (3-9) days, respectively. A Clavien-Dindo IIIa complication was experienced by 8 (10.9%) patients. Antegrade ejaculation was preserved in 90.8%. A mean number of 19 (7-68) lymph nodes were dissected. The mean number of positive lymph nodes was 1.1 (1-5), and the mean diameter of positive lymph nodes was 2.4 (0.8-4.6) cm. Eleven (14.5%) patients had stage pN0 (3/34 seminomas, 8/42 nonseminomas). In 24/27 patients (88.9%) miR371 was positive, and it was negative in 4/4 with pN0 and 3/3 (100%) with teratoma. An outfield relapse was experienced by 7 patients (9.2%), who then received salvage chemotherapy. CONCLUSION: Primary RPLND for marker-negative clinical stage IIA/B germ cell tumors results in high cure rates without adjuvant chemotherapy and is associated with a low rate of complications if performed in experienced hands. Therefore, primary RPLND should be included in the management of these patients.

[Clinical stage IIA/B seminoma - to do or not to do: the role of retroperitoneal lymphadenectomy]. / Seminom im klinischen Stadium IIA/B ­ machen oder nicht machen: welchen Stellenwert hat die retroperitoneale Lymphadenektomie?

About 10% of patients with seminomatous testicuar germ cell tumors are diagnosed with clinical stage II/B. The current guideline recommended treatment options include systemic chemotherapy with 3 cycles PEB or radiation therapy with 30 Gy for CS IIA and 36 Gy for CS IIB. Despite a high cure rate of 90-94% and 82-90% for CS IIA and CS IIB, respectively, both options are associated with a high rate of treatment-associated long-term toxicities. A significantly increased risk for the development of secondary malignancies, cardiovascular and metabolic disease as well as an increased for treatment-associated mortality has been proven in various studies. Primary nerve sparing retroperitoneal lymph node dissection (nsRPLND) has been evaluated in 5 prospective and retrospective clinical studies and it has emerged as a valid treatment alternative. The relapse-rate after a median follow-up of 25-33 months is in the range of 11-30%, so that 70-90% of patients are cured without being subjected to chemotherapy and potential long-term toxicities. All relapsing patients have been cured with secondary salvage chemotherapy. The frequency of significant surgery-associated complications is low with 3-13%. Therapeutic success depends on the surgical experience of the various surgeons and the chosen template, so that this type of surgical interventions should only be performed in centres of excellence with dedicated surgeons. Preoperative evaluation of the new biomarker miR371 has been shown to predict the presence of metastatic disease with an accuracy of around 100% so that this marker might be used in daily routine prior to active treatment in CS IIA/B seminomas.

Preservation of the native urethral plate and corpus spongiosum combined with buccal mucosa graft plus Orandi's penile skin flap as an alternative to staged urethroplasty for narrow penile strictures.

OBJECTIVE: In narrow anterior urethral strictures, the combined buccal mucosa graft (BMG) with pedicled penile skin flap (PSF) represents a well-known effective alternative to staged urethroplasty. We hypothesized that if the native urethral plate and adjacent corpus spongiosum were preserved, a narrower flap would be needed, and reinforced ventral stability could be achieved without compromising the surgical outcome. METHODS: Twelve patients with narrow penile urethral strictures underwent single-stage augmentation urethroplasty using a combined technique. A BMG was quilted to the corpora cavernosa in a dorsal onlay approach, and a longitudinal ventral PSF was transposed ventrally and sutured to the scarred native urethral mucosa on one side and to the BMG on the other side to form a neourethra of triangular form. The preserved corpus spongiosum was wrapped and fixed around the flap ventrally. RESULTS: The median age was 47 years (IQR 35-59), and the median stricture length was 5 cm (IQR 3, 8-7). The median surgical time was 205 min (IQR 172-236). The overall success rate (SR) was 91.7% without sacculation or diverticula formation after a median follow-up period of 38 months (IQR 33-40). Three transient fistulas healed through prolonged urinary diversion. Five patients (41.7%) reported postvoid dribbling following urethroplasty. CONCLUSION: Preservation of the native urethral plate is a valuable adjunct to the combination of graft and flap for single-stage augmentation urethroplasty for narrow urethral strictures, with satisfactory mid-term success and an acceptable complication rate.

Enhancing Prostate Cancer Diagnosis: Artificial Intelligence-Driven Virtual Biopsy for Optimal Magnetic Resonance Imaging-Targeted Biopsy Approach and Gleason Grading Strategy.

An optimal approach to magnetic resonance imaging fusion targeted prostate biopsy (PBx) remains unclear (number of cores, intercore distance, Gleason grading [GG] principle). The aim of this study was to develop a precise pixel-wise segmentation diagnostic artificial intelligence (AI) algorithm for tumor detection and GG as well as an algorithm for virtual prostate biopsy that are used together to systematically investigate and find an optimal approach to targeted PBx. Pixel-wise AI algorithms for tumor detection and GG were developed using a high-quality, manually annotated data set (slides n = 442) after fast-track annotation transfer into segmentation style. To this end, a virtual biopsy algorithm was developed that can perform random biopsies from tumor regions in whole-mount whole-slide images with predefined parameters. A cohort of 115 radical prostatectomy (RP) patient cases with clinically significant, magnetic resonance imaging-visible tumors (n = 121) was used for systematic studies of the optimal biopsy approach. Three expert genitourinary (GU) pathologists (Y.T., A.P., A.Q.) participated in the validation. The tumor detection algorithm (aware version sensitivity/specificity 0.99/0.90, balanced version 0.97/0.97) and GG algorithm (quadratic kappa range vs pathologists 0.77-0.78) perform on par with expert GU pathologists. In total, 65,340 virtual biopsies were performed to study different biopsy approaches with the following results: (1) 4 biopsy cores is the optimal number for a targeted PBx, (2) cumulative GG strategy is superior to using maximal Gleason score for single cores, (3) controlling for minimal intercore distance does not improve the predictive accuracy for the RP Gleason score, (4) using tertiary Gleason pattern principle (for AI tool) in cumulative GG strategy might allow better predictions of final RP Gleason score. The AI algorithm (based on cumulative GG strategy) predicted the RP Gleason score of the tumor better than 2 of the 3 expert GU pathologists. In this study, using an original approach of virtual prostate biopsy on the real cohort of patient cases, we find the optimal approach to the biopsy procedure and the subsequent GG of a targeted PBx. We publicly release 2 large data sets with associated expert pathologists' GG and our virtual biopsy algorithm.

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.

Regionalization of Testis Cancer Care-Is It Necessary?

Testicular germ cell tumors are rare genitourinary malignancies, but they represent the most common malignancies in men aged 15 to 30 years. Whereas the initial steps of management such as staging imaging studies, inguinal orchiectomy, and tumor marker can be performed elsewhere, the surgical and cytotoxic therapy needs to be done at reference centers. Regionalization of testis care has been shown to result in superior oncological outcome.

Review of Discordance Between American Urological Association and European Association of Urology Guideline Recommendations for Testicular Cancer.

We compared the American Urological Association and the European Association of Urology guidelines on testicular cancer. We identified a few differences, in particular for management of low-volume metastatic serum tumor marker-negative stage IIA/B seminoma and nonseminoma, and of advanced and relapsing disease. Overall the rate of concordance between the guidelines is high. PATIENT SUMMARY: We compared guidelines on testicular cancer published by the American Urological Association and the European Association of Urology. We found a high rate of agreement between the two guidelines, with some differences.

Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours.

BACKGROUND AND OBJECTIVE: Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. METHODS: A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. KEY FINDINGS AND LIMITATIONS: The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. PATIENT SUMMARY: The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

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.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium.

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

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%.