Downstaging and Pathological Complete Response of Locally Recurrent Sarcomatoid Renal Cell Carcinoma under Pembrolizumab and Lenvatinib: A Case Report and Review of Literature.

The advent of immune checkpoint inhibition opened new perspectives for patients with recurrent or metastasized renal cell carcinoma. In case of recurrent disease, surgical resection remains the most promising therapeutic option. Surgical resection is associated with improved overall survival and demonstrated curative potential given complete resection of metastases can be performed. This report presents the case of a patient with local recurrence of dedifferentiated sarcomatoid renal cell carcinoma approximately 1 year after initial open lumbar nephrectomy. After initial evaluation, surgical removal was deemed infeasible and an induction therapy with pembrolizumab and lenvatinib was initiated. After 3 months, corresponding to 5 cycles of pembrolizumab, the tumor showed a partial response on imaging control and was successfully resected en bloc. Histopathological examination of the specimen revealed no evidence of viable neoplastic cells. This is the first report describing a complete pathological response of a locally recurrent dedifferentiated sarcomatoid renal cell carcinoma after treatment with pembrolizumab and lenvatinib. Overall, the combination therapy was well tolerated with a maximum Common Terminology Criteria for Adverse Events Level of Two. These findings underline the potential of multimodal therapeutic strategies for recurrent renal cell carcinoma, such as induction therapies to downstage initially nonresectable masses, and highlight the need for prospective studies to allow for evidence-based treatment plans.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

[Conservative management of grade IV kidney lacerations due to stab wounds]. / Konservatives Management bei Messerstichverletzung der Niere (Grad IV).

We report on two patients who were in initially circulatory stable condition with grade IV kidney trauma after knife stab accident. Patient 1 underwent reconstructive surgery to retrieve a broken knife blade, while patient 2 was treated conservatively for bleeding that did not require intervention. Both patients could ultimately be discharged in stable condition. These case studies show that even in the case of high-grade kidney trauma with the appropriate constellation of findings, conservative management and, if exploration is necessary, a reconstructive approach is possible.

Combination of Robotic Pyeloplasty and Percutaneous Renal Surgery for Simultaneous Treatment of Ureteropelvic Junction Obstruction and Calyx Stones.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) and the simultaneous presence of kidney calyx stones represent a challenge for renal surgery. We present a novel technique for the simultaneous treatment of UPJO by robotic pyeloplasty in combination with the percutaneous endoscopic treatment of kidney calyx stones by flexible nephroscopy. PATIENTS AND METHODS: Between January 2018 and February 2020, 4 patients were diagnosed with UPJO and simultaneous pelvic or calyceal stones. UPJO was treated by conventional robotic pyeloplasty. After opening the renal pelvis, a flexible 16-French cystoscope was introduced via the 12-mm assistant trocar into the renal pelvis. The kidney calyx stones (n = 1-15) were removed endoscopically through a flexible nephroscope using a Dormia helical basket. Before suturing the anastomosis of the renal pelvis, a ureter stent was inserted. RESULTS: After the procedure, all patients were stone free. Using the Clavien-Dindo classification, no complications were noted. The mean size of the calculi was 6.69 mm (range: 1-25). Up to 15 calyx stones (mean 3.46) were removed per patient. A complete stone clearance confirmed by postoperative X-ray imaging was achieved in all patients. The mean operative time was 149 min (range: 130-178). Mean hospital stay was 7 days (7-8). The urethral stent was removed after 4-6 weeks. CONCLUSIONS: Robotic management of UPJO and simultaneous flexible nephroscopy for removal of calyceal stones is an effective treatment in 1 session. Combining robotic surgery with flexible percutaneous renal surgery is a feasible, safe, and effective method of the treatment of UPJO and concomitant calyceal stones.

External validation of novel magnetic resonance imaging-based models for prostate cancer prediction.

OBJECTIVES: To validate, in an external cohort, three novel risk models, including the recently updated European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator, that combine multiparametric magnetic resonance imaging (mpMRI) and clinical variables to predict clinically significant prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively analysed 307 men who underwent mpMRI prior to transperineal ultrasound fusion biopsy between October 2015 and July 2018 at two German centres. mpMRI was rated by Prostate Imaging Reporting and Data System (PI-RADS) v2.0 and clinically significant PCa was defined as International Society of Urological Pathology Gleason grade group ≥2. The prediction performance of the three models (MRI-ERSPC-3/4, and two risk models published by Radtke et al. and Distler et al., ModRad and ModDis) were compared using receiver-operating characteristic (ROC) curve analyses, with area under the ROC curve (AUC), calibration curve analyses and decision curves used to assess net benefit. RESULTS: The AUCs of the three novel models (MRI-ERSPC-3/4, ModRad and ModDis) were 0.82, 0.85 and 0.83, respectively. Calibration curve analyses showed the best intercept for MRI-ERSPC-3 and -4 of 0.35 and 0.76. Net benefit analyses indicated clear benefit of the MRI-ERSPC-3/4 risk models compared with the other two validated models. The MRI-ERSPC-3/4 risk models demonstrated a discrimination benefit for a risk threshold of up to 15% for clinically significant PCa as compared to the other risk models. CONCLUSION: In our external validation of three novel prostate cancer risk models, which incorporate mpMRI findings, a head-to-head comparison indicated that the MRI-ERSPC-3/4 risk model in particular could help to reduce unnecessary biopsies.

Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

BACKGROUND: Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited. METHODS: Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017. RESULTS: Of 46 identified patients 39.1 % had a prior diagnosis of prostatic adenocarcinoma only, 43.5 % had a mixed differentiation at NEPC diagnosis, 67.4 % developed visceral metastases, 10.9 % showed paraneoplastic syndromes. Overall survival (OS) from NEPC diagnosis was 15.5 months, and significantly shorter in patients with a prior prostatic adenocarcinoma (5.4 vs. 32.7 months, p=0.005). 34 patients received palliative first-line systemic therapy with a median progression-free survival (PFS) of 6.6 months, mostly PE. Overall response rate (ORR) for PE was 48.1 %. 19 patients received second-line therapy, mostly with poor responses. Active regimens were topotecan (1 PR, 3 PD), enzalutamide (1 SD), abiraterone (1 SD), FOLFIRI (1 SD), and ipilimumab+nivolumab (1 PR). One patient with prostatic carcinoid was sequentially treated with octreotide, peptide receptor radionuclide therapy and everolimus, and survived for over 9 years. CONCLUSIONS: EP in first-line shows notable ORR, however limited PFS. For second-line therapy, topotecan, FOLFIRI, enzalutamide, abiraterone and immune checkpoint blockade are treatment options. Prostatic carcinoids can be treated in analogy to well differentiated gastrointestinal NETs.