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Objective: To evaluate the effectiveness and safety profile of the tyrosine kinase inhibitor Axitinib for patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Methods: Adult patients from the German non-interventional post-approval multicenter STAR-TOR registry with a/mRCC (NCT00700258) were included if treated with Axitinib in second line or beyond. Overall survival (OS), progression-free survival (PFS) and adverse events were evaluated across subgroups using descriptive statistics and survival analyses. Results: Between November 2012 and December 2020, 75 study sites recruited 210 patients treated with Axitinib (69,6% male; median age 69 years; median Karnofsky Index 80%). Clear cell RCC was the most frequent histological subtype (81.0%). Axitinib was administered as second-line in 51.4%, third-line in 24.8%, and fourth-line treatment and beyond in 23.8% of the patients, respectively. MSKCC score was 15.0% favorable, 33.6% intermediate, and 51.3% poor risk. Median PFS was 5.6 months, and median OS 18.3 months. Patients with lactate dehydrogenase (LDH) levels > 300U/l had a nominally significantly shorter OS than patients with LDH≤300U/l (8.2 vs. 19.0 months, p = 0.008). Drug related adverse and serious adverse events were reported in 56.7% and 17.6% of the patients, respectively (most common adverse event: gastrointestinal disorders; 37.6%). Conclusions: This real-world study confirms the clinical relevance of Axitinib in the second-line and beyond setting for a/mRCC with OS and PFS reported in concordance with pivotal trials, while demonstrating a favorable safety profile. A high LDH serum level could be a negative predictive marker for Axitinib effectiveness, which can aid in clinical decision making.

The outbreak of the COVID-19 pandemic led demand for online grocery orders for both click & collect (C&C) and attended home delivery (AHD) to outstrip delivery capacity by a wide margin. In the United Kingdom, the booking systems of some e-retailers could not handle the flood of incoming requests, forcing the retailers to proactively reach out to certain priority customer segments with the aim of serving as many high-priority customers as possible. To determine when to contact each customer segment in this extraordinary demand environment, we investigate the new demand management concept of proactively contacting customers. We first develop a decision policy for the C&C fulfillment method to address the problem of when to contact customers. We then extend this approach to the AHD setting. To cope with increased problem complexity, we propose a three-step procedure to solve this problem. First, we subdivide the delivery area into smaller subareas; second, we select the most promising subareas; and third, we determine which customers to contact within the chosen subareas. To gain managerial insights and to show the practical benefits of our approaches, we apply both approaches to realistic data from the London area. Our results show that proactive customer contacting allows for a tailored allocation of scarce capacity in e-groceries. We conclude with a discussion on how these contacting techniques can be valuable in postcrisis times. History: This paper has been accepted for the Service Science Special Issue on Innovation in Transportation-Enabled Urban Services.

ZusammenfassungIm hier vorgestellten Fall wird von einem 29-jährigen Mann berichtet, der sich aufgrund eines Traumas als Kleinkind und nach mehrmaligen Vor-Operationen mit einer kontinenten Harnableitung mittels Mainz Pouch I und Z.n. Zystektomie vorstellte. Grund der Vorstellung war eine unspezifische Schwellung paraumbilikal rechts, welche für den Patienten eine Beeinträchtigung darstellte. Trotz weiterführender Bildgebung mittels Magnetresonanztomographie blieb eine eindeutige Diagnose des im subkutanen Gewebe gelegenen Verhaltes aus. Nach chirurgischer Entfernung des kompletten Befundes und nach histologischer Aufarbeitung konnte die Diagnose einer Urachuszyste gestellt werden.

This case presents a 29-year-old man, with a urinary diversion via MAINZ Pouch I after cystectomy due to trauma in early childhood with a history of multiple previous surgeries. The reason for the presentation was a non-specific paraumbilical swelling on the right, which was disturbing for him. Despite further diagnostics by means of magnetic resonance imaging, a clear diagnosis of the subcutaneous tissue could not be made. After surgical removal of the complete cyst and after histological work-up, the diagnosis of an urachus-cyst could be made.Im hier vorgestellten Fall wird von einem 29-jährigen Mann berichtet, der sich aufgrund eines Traumas als Kleinkind und nach mehrmaligen Vor-Operationen mit einer kontinenten Harnableitung mittels Mainz Pouch I und Z.n. Zystektomie vorstellte. Grund der Vorstellung war eine unspezifische Schwellung paraumbilikal rechts, welche für den Patienten eine Beeinträchtigung darstellte. Trotz weiterführender Bildgebung mittels Magnetresonanztomographie blieb eine eindeutige Diagnose des im subkutanen Gewebe gelegenen Verhaltes aus. Nach chirurgischer Entfernung des kompletten Befundes und nach histologischer Aufarbeitung konnte die Diagnose einer Urachuszyste gestellt werden.

Introduction: The aim of this study was to test for differences in overall (OS) and progression-free survival (PFS) rates and toxicity in first-line immune checkpoint inhibition (IO) combination therapy in metastatic renal-cell carcinoma (mRCC) patients. Methods: Between November 2017 and April 2021, 104 patients with histologically confirmed mRCC from 6 tertiary referral centers with either IO + IO (nivolumab + ipilimumab, n = 68) or IO + tyrosine kinase inhibitor (TKI) (pembrolizumab + axitinib, n = 36) were included. Kaplan-Meier and Cox regression analyses tested for OS and PFS differences. Results: Of 104 mRCC patients, 68 received IO + IO (65.4%) and 36 IO + TKI (34.6%) therapy, respectively. Median age was 67 years (interquartile range: 57–70.3). Patients receiving IO + TKI were less likely to be poor risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium score (16.7 vs. 30.9%) and presented with lower T-stage, compared to IO + IO treated patients. Median PFS was 9.8 months (CI: 5.3–17.6) versus 12.3 months (CI: 7.7 – not reached) for IO + IO versus IO + TKI treatment, respectively (p = 0.22). Median OS was not reached, survival rates at 12 months being 73.9 versus 90.0% for IO + IO versus IO + TKI patients (p = 0.089). In subgroup analyses of elderly patients (≥70 years, n = 38), IO + TKI treatment resulted in better OS rates at 12 months compared to IO + IO (91.0 vs. 57.0%; p = 0.042). Conclusion: IO + IO and IO + TKI as first-line therapies in mRCC patients were both comparable as for the oncological outcome and toxicity.

Elective scrotal surgery is associated with a high rate of postoperative complications. There is no specific recommendation for postoperative care.We investigated whether support underwear has an impact on postoperative complications and quality of life.From July 2020 to November 2021, patients with prior elective scrotal surgery were randomized into the intervention group "support underwear" or the control group. In addition to patient characteristics, intraoperative and postoperative findings were documented. The primary endpoint comprised postoperative complications. Secondary endpoints were prolonged length of hospital stay, emergency visits, unplanned readmissions, increased use of analgesics, and quality of life, which was recorded using the EQ5D (European Quality of Life 5 Dimensions) questionnaire preoperatively, on day 1 and 4 weeks postoperatively.Data from 50 patients were analyzed. The mean age was 46.7 years (standard deviation [SD] 18.6). Inguinal surgery with/without orchiectomy (52%), hydrocele resection (22%), or ligation of varicocele (14%) were performed most frequently. The mean operating time was 62.8 min (SD 35.2); length hospital stay was 2.6 days (SD 1.2). In all, 20% of the patients suffered a postoperative complication. Type of surgery was significantly associated with postoperative complications (p = 0.01) and unplanned readmission (p = 0.04). Regarding biometric and perioperative data, there were no significant differences between the interventional group (n = 27) and control group (n = 23).A nonnegligible number of complications occurs after elective scrotal surgery. Complications affects quality of life up to 4 weeks after the surgery. Postoperative care with support underwear does not appear to affect the postoperative complication rate, but it positively influences the quality of life in patients with scrotal access.HINTERGRUND: Elektive skrotale Eingriffe sind mit einer hohen Rate an postoperativen Komplikationen verbunden. Eine besondere Empfehlung zur postoperativen Versorgung gibt es nicht.Wir untersuchten den Einfluss einer stützenden Herrenunterhose auf postoperative Komplikationen und Lebensqualität.Von 07/2020 bis 11/2021 wurden Patienten vor elektiver skrotaler Operation in die Interventionsgruppe „stützende Herrenunterhose“ oder die Kontrollgruppe randomisiert. Neben Basischarakteristika der Patienten wurden intraoperative und postoperative Befunde erfasst. Der primäre Endpunkt umfasste postoperative Komplikationen. Sekundäre Endpunkte waren verlängerter Krankenhausaufenthalt, ungeplante Wiedervorstellungen/-aufnahmen, gesteigerter Analgetikabedarf und die gesundheitsbezogene Lebensqualität, welche mittels EQ5D-Fragebogen präoperativ, am 1. Tag und 4 Wochen postoperativ erfasst wurde.Daten von 50 Patienten konnten ausgewertet werden. Das mittlere Alter betrug 46,7 Jahre (Standardabweichung [SD] 18,6). Am häufigsten wurden inguinale Hodenfreilegungen mit/ohne Ablatio testis (52 %), Hydrozelenresektionen (22 %) oder Varikozelenligaturen (14 %) durchgeführt. Die mittlere Operationsdauer betrug 62,8 (SD 35,2) min, die stationäre Verweildauer 2,6 (SD 1,2) Tage. 20 % der Patienten erlitten eine postoperative Komplikation. Die Art des Eingriffs korrelierte signifikant mit dem Auftreten von postoperativen Komplikationen (p = 0,01), ungeplanter ambulanter Wiedervorstellung (p = 0,001) und Wiederaufnahme (p = 0,04). Hinsichtlich biometrischer und perioperativer Daten zeigten sich keine signifikanten Unterschiede zwischen Interventionsgruppe (n = 27) und Kontrollgruppe (n = 23).Nach elektiven skrotalen Eingriffen tritt eine nicht zu vernachlässigende Anzahl an Komplikationen auf. Das Auftreten von Komplikationen beeinflusst den subjektiven Gesundheitszustand noch 4 Wochen nach der Operation. Die postoperative Versorgung mit einer stützenden Unterhose scheint keinen Einfluss auf die postoperative Komplikationsrate zu haben, jedoch beeinflusst sie die Lebensqualität bei Patienten mit skrotalem Zugang positiv.

Aim: Examine the effects of baseline hypertension (HTN) and statin or proton pump inhibitor (PPI) use on sunitinib treatment outcomes in STAR-TOR, a real-world registry. Materials & methods: Presence or absence of HTN and use or nonuse of statins or PPIs were determined at registry entry. End points included overall survival (OS) and progression-free survival (PFS). Results: Data were from 557 patients. Presence or absence of HTN did not affect OS or PFS. PFS (median [95% CI]) was longer in statin users (9.4 [6.5–13.6] months) versus nonusers (6.9 [5.7–8.2] months) (p = 0.0442). OS was shorter in PPI users (20.2 [14.9–28.3] months) versus nonusers (25.7 [22.7–33.0] months) (p = 0.0212). Conclusion: Comorbidities and comedications may affect real-world sunitinib treatment outcomes. Clinical Trial Registration: NCT00700258 ( ClinicalTrials.gov )

Background Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was shown to be clinically active and tolerable in patients with advanced urothelial carcinoma and prespecified FGFR alterations in the primary analysis of the BLC2001 study at median 11 months of follow-up. We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study. Methods The open-label, non-comparator, phase 2, BLC2001 study was done at 126 medical centres in 14 countries across Asia, Europe, and North America. Eligible patients were aged 18 years or older with locally advanced and unresectable or metastatic urothelial carcinoma, at least one prespecified FGFR alteration, an Eastern Cooperative Oncology Group performance status of 0–2, and progressive disease after receiving at least one systemic chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy or were ineligible for cisplatin. The selected regimen determined in the initial part of the study was continuous once daily 8 mg/day oral erdafitinib in 28-day cycles, with provision for pharmacodynamically guided uptitration to 9 mg/day (8 mg/day UpT). The primary endpoint was investigator-assessed confirmed objective response rate according to Response Evaluation Criteria In Solid Tumors version 1.1. Efficacy and safety were analysed in all treated patients who received at least one dose of erdafitinib. This is the final analysis of this study. This study is registered with ClinicalTrials.gov, NCT02365597. Findings Between May 25, 2015, and Aug 9, 2018, 2328 patients were screened, of whom 212 were enrolled and 101 were treated with the selected erdafitinib 8 mg/day UpT regimen. The data cutoff date for this analysis was Aug 9, 2019. Median efficacy follow-up was 24·0 months (IQR 22·7–26·6). The investigator-assessed objective response rate for patients treated with the selected erdafitinib regimen was 40 (40%; 95% CI 30–49) of 101 patients. The safety profile remained similar to that in the primary analysis, with no new safety signals reported with longer follow-up. Grade 3–4 treatment-emergent adverse events of any causality occurred in 72 (71%) of 101 patients. The most common grade 3–4 treatment-emergent adverse events of any cause were stomatitis (in 14 [14%] of 101 patients) and hyponatraemia (in 11 [11%]). There were no treatment-related deaths. Interpretation With longer follow-up, treatment with the selected regimen of erdafitinib showed consistent activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations.

Introduction: Inhibition of neo-angiogenesis is a cornerstone of medical treatment in metastatic renal cell carcinoma (mRCC). While 1st line therapies were previously dominated by inhibitors of the vascular endothelial growth factor axis, 2nd line options were less clearly defined. We investigated the role of everolimus (EVE) or a tyrosine kinase inhibitor (TKI) in 2nd line treatment of mRCC patients. Methods: Key inclusion criteria were measurable mRCC, ECOG 0–1, IMDC risk: good or intermediate and adequate organ function. Patients who progressed on or were intolerant to bevacizumab + interferon were subject for randomization between TKI and EVE treatment. Cross-over occurred at time of progression during 2nd line treatment. Improvement of 2nd line progression-free survival (PFS) rate (PFR) at 6 months from 50% to 65% was the primary endpoint. Secondary endpoints were PFS, total PFS, objective response rate (ORR), overall survival (OS), safety, and patient reported outcomes. Results: In 2012–2015, a total of 22 patients were included. The study was stopped for poor accrual. Ten patients (46%) were randomized to receive 2nd line treatment with EVE (n = 5) or axitinib (n = 4)/sunitinib (n = 1). ECOG 0 was recorded in 20% (EVE) and 60% (TKI). Severe adverse events occurred in approx. 60% in each arm. ORR was 1/5 (20%) for TKI and 0/5 (0%) for EVE. PFR at 6 months was 20% in each arm. Median PFS was 3.7 months (EVE) and 2.2 months (TKI) (hazard ratio [HR] 1.0 [95% confidence interval [CI]: 0.26–3.85]). The OS was comparable between arms HR 1.12 (95% CI: 0.27–4.61). Conclusion: The rapid change of the treatment landscape, the limited use of bevacizumab and interferon in 1st line and the duration of 1st line treatment jeopardized BERAT trial recruitment. The small number of patients is a major limitation of our trial. Our observation indicated the poor prognosis in progressive patients and the limited efficacy of TKI or mTOR inhibitors in 2nd line treatment.

Radium-223 verlangert das Gesamtuberleben und erhalt die Lebensqualitat von Patienten mit metastasiertem kastrationsresistentem Prostatakarzinom (mCRPC) und symptomatischen Knochenmetastasen ohne bekannte Viszeralmetastasen. Kombiniert mit einem LHRH-Analogon kann Radium-223 in der therapeutischen Sequenz eingesetzt werden, wenn die Erkrankung nach Erhalt von zwei vorausgehenden systemischen Therapien fortschreitet oder wenn keine andere verfugbare systemische Therapie fur den Patienten geeignet ist. Bei der Behandlung des Prostatakarzinoms stehen Arzte heute vor einer ungewohnten Vielfalt und Komplexitat der therapeutischen Optionen. Eine Fulle von Studienresultaten tragt zur Dynamik der therapeutischen Landschaft bei. Radium-223 wurde Ende 2013 zur mCRPC-Therapie zugelassen. Die Anwendungsempfehlungen wurden inzwischen mehrfach angepasst. Vor dem Hintergrund aktueller Studien und Erfahrungen im klinischen Alltag sondiert der Artikel die Position von Radium-223 in der therapeutischen Sequenz und skizziert Eckpunkte fur die interdisziplinare Zusammenarbeit zwischen Uroonkologen und Nuklearmedizinern. Radium-223 wirkt androgenrezeptorunabhangig und ist daher eine Option, wenn in der therapeutischen Sequenz andere Wirkstoffe resistenzbedingt nur begrenzt wirksam sind. Auch ist durch Radium-223 keine Wirkungsabschwachung oder -verstarkung der Vor- und Folgemedikation zu erwarten. Die Chance fur eine androgenrezeptorunabhangige und lebensverlangernde Therapie sollte genutzt werden, sobald die Kriterien fur eine Behandlung mit Radium-223 erfullt sind. Denn im Krankheitsverlauf nimmt die Wahrscheinlichkeit fur das Auftreten viszeraler Metastasen zu. Der praventive Einsatz von Bisphosphonaten oder Denosumab ist entsprechend der aktuellen Leitlinien beim mCRPC zu empfehlen, bevor eine Behandlung mit Radium-223 begonnen oder wieder aufgenommen wird.

Die transurethrale konvektive interstitielle Wasserdampfablation ist ein innovatives minimalinvasives Verfahren zur operativen Therapie der benignen Prostatahyperplasie. Auf Basis der bislang vorliegenden Ergebnisse fur das Verfahren soll der Stellenwert der Methode im Kontext der sonstigen verfugbaren therapeutischen Masnahmen diskutiert werden.

The importance of PSMA PET/CT in both primary diagnostics and prostate cancer recurrence has grown steadily since its introduction more than a decade ago. Over the past years, a vast amount of data have been published on the diagnostic accuracy and the impact of PSMA PET/CT on patient management. Nevertheless, a large heterogeneity between studies has made reaching a consensus difficult; this review aims to provide a comprehensive clinical review of the available scientific literature, covering the currently known data on physiological and pathological PSMA expression, influencing factors, the differences and pitfalls of various tracers, as well as the clinical implications in initial TNM-staging and in the situation of biochemical recurrence. This review has the objective of providing a practical clinical overview of the advantages and disadvantages of the examination in various clinical situations and the body of knowledge available, as well as open questions still requiring further research.

Aim: Examine outcomes in sunitinib-treated patients by International Metastatic RCC Database Consortium (IMDC) or Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors. Patients & methods: Patients enrolled in STAR-TOR registry (n = 327). End points included overall survival, progression-free survival and objective response rate. Results: Overall survival was similar for IMDC 0 versus 1 (p = 0.238) or 2 versus ≥3 (p = 0.156), but different for MSKCC (0 vs 1, p = 0.037; 2 vs ≥3, p = 0.001). Progression-free survival was similar for IMDC 2 versus 3 (p = 0.306), but different for MSKCC (p = 0.009). Objective response rate was different for IMDC 1 (41.9%) and 2 (29.5%) and similar for MSKCC 1 (34.4%) and 2 (31.0%). Conclusion: Outcome data varied according to IMDC or MSKCC. MSKCC model accurately stratify patients into risk groups. Clinical trial registration: NCT00700258 (ClinicalTrials.gov)

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Purpose: Several studies have demonstrated an advantage of 68Ga-PSMA-PET/CT as staging modality for detection of prostate cancer (PCa) metastases. Data concerning metastatic manifestation and impact on PCa development of mesorectal lymph nodes (MLN) is limited. Our investigation describes MLN metastases as index lesion in 68Ga-PSMA PET/CT imaging for recurrent PCa. Methods: Twelve PCa patients with biochemical recurrence (BCR) after primary therapy who prospectively underwent a baseline 68Ga-PSMA-PET/CT initially showed MLN metastases. Eight of these patients received a follow-up 68Ga-PSMA-PET/CT to evaluate treatment response and further evolution. Prostate-specific antigen (PSA)-levels, changes in PSMA-uptake of MLN metastases and further 68Ga-PSMA PET/CT findings were recorded. Results: Median PSA at the first 68Ga-PSMA-PET/CT was 5.39 ng/ml. In all patients therapeutic management changed after the first 68Ga-PSMA-PET/CT. Androgen deprivation therapy (ADT) was initiated in seven of eight patients, one patient restarted initial ADT. Three patients additionally received salvage radiation therapy (sRT) including the prostatic lodge and docetaxel chemotherapy was started in one case. At follow-up, a decrease of PSA-level was detected in all patients (median 2.05 ng/ml) after median 10 months. In six of eight patients we observed a decrease or complete regress of PSMA-uptake in MLN in the follow-up 68Ga-PSMA-PET/CT. Conclusion: MLN metastases detected by 68Ga-PSMA-PET/CT seem to be a relevant localization of tumor manifestation and may serve as index lesion in the treatment of recurrent PCa. Besides the known oncological benefits of ADT and sRT, in case of sole MLN metastases individualized therapy like salvage lymphadenectomy or RT with a defined radiation field could be options for these patients.

Background: Limited data are available for the use of agents in metastatic castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide data during treatment with cabazitaxel (CAB), helping to improve the informed-consent process. Patients and Methods: We retrospectively reviewed patients treated with fourth-line or beyond CAB for mCRPC after failure of previous therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223. The progression-free survival (PFS) and the overall survival (OS) were estimated using the Kaplan-Meier method and compared to published data based on a structured literature review. The hospitalization rate was recorded. Factors influencing 6-months OS were analyzed. Results: Fifteen patients were identified at 4 institutions and included in the analysis. The median PFS was 104 days (range 47-397 days). The median time to death was 10 months (range 2-16). PFS and OS data are in accordance with 17 published patients so far. During the therapy, eleven (73%) of the patients were hospitalized. Prostate-specific antigen (PSA, 500 units; hazards ratio [HR] 1.491, 95% CI 1.000-2.0175), white blood cell count (HR 0.425, 95% CI 0.108-0.952), hemoglobin (HR 0.6014, 95% CI 0.2942-1.0758), and alkaline phosphatase (100 units; HR 1.0964, 95% CI 1.000-1.2859) correlate with 6-months OS. Conclusions: CAB beyond the third-line is often accompanied by hospitalization. PFS is a significant proportion of the median time of OS. The baseline laboratory might be a good indicator for the decision between CAB and best-supportive care.

Background Multiple surgical treatment options are available for the treatment of ureteropelvic junction obstruction (UPJO). The aim of this study is to compare the most frequently used technics in a comprehensive network approach. Methods A systematic literature search of the EMBASE, MEDLINE and COCHRANE libraries was conducted in January 2018. Publications were included that evaluated at least two of the following surgical techniques: open pyeloplasty (OP), endopyelotomy (EP), laparoscopic (LP) and robot assisted pyeloplasty (RP). Main outcomes were operative success, complications, urinary leakage, re-operation, transfusion rate, operating time, and length of stay. Network meta-analyses with random effects models simultaneously assessed effectiveness of all surgical techniques. Results A total of 26 studies including 3143 patients were analyzed. Compared with RP, EP and LP showed lower operative success rates (EP: OR = 0.09, 95%CI:0.05–0.19; p

INTRODUCTION AND OBJECTIVES:Left and right kidney differ with respect to anatomical position, arterial supply and venous as well as lymphatic drainage. Our study aims to evaluate whether these diff...

177Lu-PSMA radioligand therapy is a promising new option for patients with metastasized castration-resistant prostate cancer, and the spectrum of adverse events with this treatment has to be evaluated. Here, we describe the case of a patient with M1c disease (metastasis to the mediastinum, lungs, bones, and liver) who presented with elevated liver enzyme levels after receiving 177Lu-PSMA radioligand therapy for castration-resistant prostate cancer. Pretreatment 68Ga-PSMA PET/CT showed at least 4 liver lesions with low uptake. Overall, the liver uptake was inhomogeneous. Liver biopsy was performed subsequently.

BACKGROUND Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by 68Ga-PSMA-PET/CT. METHODS We retrospectively analyzed 76 consecutive PCa patients who underwent 68Ga-PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa. RESULTS We detected PET-positive lesions for PCa in 68Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31–13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6–93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4–21]; longest diameter median 7.5 mm [range 5–25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy. CONCLUSIONS Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. 68Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes. Prostate © 2016 Wiley Periodicals, Inc.

631 Background: Sunitinib remains an important treatment option for mRCC, but the effect of comorbidities/comedications on sunitinib treatment outcomes have not been fully explored. Methods: Data were collated from STAR-TOR, an ongoing real-world registry. Cutoff date for analysis was 19 June 2019. This subgroup analysis assessed the presence or absence of hypertension (HTN), and the use or non-use of statins and proton pump inhibitors (PPIs), determined at the time of entry to the registry. Treatment endpoints were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). OS and PFS were analyzed by Kaplan-Meier methods. Differences within subgroups were tested using Log-rank test for OS and PFS, and Fisher’s exact test for ORR. Results: 557 sunitinib-treated pts were analyzed; 366 had HTN and 191 did not, 130 used statins and 427 did not, and 165 used PPIs and 392 did not. Median (m) OS (95% confidence intervals) was similar in pts with and without HTN (25.4 [21.1, 31.5] vs 21.5 [15.2, 28.0] months; p = 0.215). mPFS (8.0 [6.5, 9.9] vs 6.3 [5.4, 8.2] months; p = 0.140) and ORR (31.2% vs 30.9%; p = 1.000) were also similar in pts with and without HTN. mOS was similar in pts who used statins vs those who did not (27.8 [20.2, 35.4] vs 24.0 [19.4, 27.3] months; p = 0.884), while mPFS was significantly longer in pts who used statins (9.4 [6.5, 13.6] vs 6.9 [5.7, 8.2] months; p = 0.044). ORR was 37.8% vs 29.0% in pts who did and did not use statins (p = 0.072). mOS was significantly shorter in pts who used PPIs vs those who did not (20.2 [14.9, 28.3] vs 25.7 [22.7, 33.0] months; p = 0.021). mPFS (5.8 [4.6, 8.2] vs 8.0 [6.5, 9.8] months; p = 0.091) and ORR (26.6% vs 33.0%; p = 0.177) were similar in pts who did and did not use PPIs. Conclusions: In sunitinib-treated pts with mRCC in a real-world registry, mPFS was significantly longer and there was a trend toward better ORR in pts who used statins, whereas mOS was significantly shorter and there was a trend toward shorter mPFS in pts who used PPIs. Common comedications may affect sunitinib treatment outcomes in pts with mRCC.

628 Background: Metastatic renal cell carcinoma (mRCC) treatment is partly informed by risk group. The two most commonly used prognostic models, the International Metastatic RCC Database Consortium (IMDC) and the Memorial Sloan-Kettering Cancer Center (MSKCC), stratify patients (pts) into favorable (0 risk factors [RFs]), intermediate (1–2 RFs) or high risk (≥3 RFs) groups. This study examined real-world outcomes according to IMDC and MSKCC RFs in sunitinib-treated pts with mRCC. Methods: Data were extracted on 19 June 2019 from a large, prospective German multicenter registry (STAR-TOR). Only pts with sufficient data for risk stratification by IMDC and MSKCC were included in this analysis. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of RFs on survival was assessed using Cox’s regression analysis and the chi square test. Results: According to IMDC or MSKCC, 16.7% and 15.3%, 26.2% and 30.8%, 18.7% and 24.7%, and 38.5% and 29.2 of pts had 0, 1, 2 and ≥3 RFs, respectively. In IMDC intermediate pts, only < 1 year diagnosis to therapy (24.8%) was the most common RF; in MSKCC intermediate pts, < 1 year diagnosis to therapy with low hemoglobin (19.9%) were the most common. OS was not significantly different for pts with 0 vs 1 (p = 0.24), or 2 vs ≥3 (p = 0.16) IMDC RFs, but was significant according to MSKCC RFs (0 vs 1, p = 0.04; 2 vs ≥3, p < 0.01). OS was significantly longer for pts with 1 vs 2 RFs for IMDC (p = 0.03) and MSKCC (p = 0.04), but PFS was not (IMDC, p = 0.29; MSKCC, p = 0.12). OS was significantly longer for 0 vs 2, 0 vs ≥3, and 1 vs ≥3 RFs for IMDC and MSKCC RFs (all comparisons, p < 0.01). Similar results were observed for PFS with the exception of 0 vs 1 IMDC RF (p = 0.01). Conclusions: The intermediate risk group appears to be heterogeneous. OS for pts with 1 RF may align with the favorable risk group and pts with 2 RFs may align with the poor risk group.[Table: see text]

To compare partial nephrectomy (PN), radiofrequency ablation (RFA), cryoablation (CRA) and microwave ablation (MWA) regarding oncologic, perioperative and functional outcomes. The MEDLINE, EMBASE and COCHRANE libraries were searched for studies comparing PN, RFA, CRA or MWA and reporting on any-cause or cancer-specific mortality, local recurrence, complications or renal function. Network meta-analyses were performed. Forty-seven studies with 24,077 patients were included. Patients receiving RFA, CRA or MWA were older and had more comorbidities compared with PN. All-cause mortality was higher for CRA and RFA compared with PN (incidence rate ratio IRR = 2.58, IRR = 2.58, p < 0.001, respectively). No significant differences in cancer-specific mortality were evident. Local recurrence was higher for CRA, RFA and MWA compared with PN (IRR = 4.13, IRR = 1.79, IRR = 2.52, p < 0.05 respectively). A decline in renal function was less pronounced after RFA versus PN, CRA and MWA (mean difference in GFR MD = 6.49; MD = 5.82; MD = 10.89, p < 0.05 respectively). Higher overall survival and local control of PN compared with ablative therapies did not translate into significantly better cancer-specific mortality. Most studies carried a high risk of bias by selecting younger and healthier patients for PN, which may drive superior survival and local control. Physicians should be aware of the lack of high-quality evidence and the potential benefits of ablative techniques for certain patients, including a superior complication profile and renal function preservation. • Patients selected for ablation of small renal masses are older and have more comorbidities compared with those undergoing partial nephrectomy. • Partial nephrectomy yields lower all-cause mortality, which is probably biased by patient selection and does not translate into prolonged cancer-free survival. • The decline of renal function is smallest after radiofrequency ablation for small renal masses.

BACKGROUND The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by 68Ga-PSMA PET/CT. METHODS Retrospective analysis of 35 PCa patients underwent 68Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n = 23) or before primary therapy of high-risk PCa (n = 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18–30) and 19.5 ng/ml (range 6–90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4–17) and 12 (range 8–29) per patient and the median number of positive lymph nodes was 1 (range 1–2) and 3 (2–3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by 68Ga-PSMA PET/CT. The use of 68Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies. Prostate 75:1934–1940, 2015. © 2015 Wiley Periodicals, Inc.

To evaluate survival of patients with localized T1a clear cell renal cell carcinoma (ccRCC) who received cryosurgery or thermal ablation compared to deferred therapy. We included 733 patients with histopathologically confirmed localized T1a ccRCC who either received cryosurgery (n = 315) or thermal ablation (n = 155), as well as patients who deferred therapy (n = 263) from the 2000–2013 Surveillance, Epidemiology, and End Results Program urinary cancer file. Cox proportional hazard models were used to compare cancer-specific survival (CSS) across subgroups. Sensitivity analyses were conducted to assess potential unmeasured confounding by comorbidities. Patients treated with cryosurgery and thermal ablation had a statistically significant CSS benefit compared to those who deferred therapy (cryosurgery HR 0.25, 95% CI 0.14–0.45, p

Context The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non–muscle-invasive UCB. Objective To conduct a meta-analysis evaluating gender-specific differences in recurrence of non–muscle-invasive urinary bladder cancer (NMIBC). Evidence acquisition An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggers test. Evidence synthesis Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01–1.23, p =0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13–2.39, p =0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32–2.15, p Conclusions Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. Patient summary In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men.

Background Antacids (AA) are commonly used in the elderly population. Proton pump inhibitors and other drugs to neutralize the gastral pH level and to prevent gastroesophageal reflux are suspected to reduce the efficacy of tyrosine kinase inhibitors. To our knowledge, the effect of AA therapy on SUN efficacy has not been investigated in a real-world mRCC population yet. Methods STAR-TOR is a German multicenter registry for pts with mRCC (NCT00700258) which was amended to include SUN pts in June 2010 with regulatory and ethic committee’s approval. Objectives are the evaluation of the safety profile, the tolerability and anti-tumor activity of SUN. Here, we present data on the impact of AA therapy on the therapeutic efficacy of SUN in first-line mRCC pts. Results From July 2010 to February 2019, 109 active study sites recruited 550 first line SUN pts. 378 (69%)of these were reported to use AA therapy at baseline, 172 (31%) were AA non-users. Characteristics (AA yes/no): male 66.1/75.1%, median age 67.0/68.0 years, clear cell component: 81.4/81.5%. For all 550 pts, most common drug-related toxicities (incidence ≥ 15%) of any grade were gastrointestinal disorders (38.0%), general disorders including fatigue, mucosal inflammation and edema (29.1%), skin and subcutaneous tissue disorders including hand-foot syndrome (22.7%), nervous system disorders, and blood and lymphatic system disorders (both 19.1%). There was no relevant difference in adverse event rates between AA users and non-users. Efficacy (AA yes vs no): overall response rate 15.1 vs 27.4% (n = 426, p = 0.007), PFS 5.8 vs 8.0 months (mo), p = 0.11; OS 20.3 vs 25.7 mo, p = 0.01. Conclusions In our real-world data set, we found a relevant efficacy difference between SUN-treated first-line mRCC pts who used AA therapy at baseline compared with AA non-users, especially in terms of OS. This should be taken into account when prescribing SUN in this setting. Clinical trial identification NCT00700258. Legal entity responsible for the study Pfizer Pharma GmbH, Berlin, Germany. Funding Pfizer Pharma GmbH, Berlin, Germany. Disclosure K. Schlack: Advisory / Consultancy: Roche, Ipsen, Amgen, Novartis; Travel / Accommodation / Expenses: Bayer, Ipsen, Astellas, Takeda, Pfizer, Sanofi, Janssen-Cilag. M. Boegemann: Honoraria (self): Pfizer, Eisai, MSD, BMS, Ipsen, Eusa Pharma, Novartis. M. Woike: Full / Part-time employment: Pfizer Pharma GmbH. G. Krekeler: Full / Part-time employment: Pfizer Pharma GmbH. T. Fischer: Full / Part-time employment: Winicker-Norimed GmbH. L. Bergmann: Research grant / Funding (institution): BMS; Advisory / Consultancy: BMS, Eusa, Ipsen, Novartis, Pfizer, Roche. M. Rink: Advisory / Consultancy: BMS, Ipsen, MSD, Novartis, Pfizer, Roche. A. Strauss: Advisory / Consultancy: Bayer, MBS, Eisai, Novartis, Pfizer, Roche; Honoraria (self): Amgen, Bayer, BMS, Eisai, Ipsen, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis; Travel / Accommodation / Expenses: Ipsen, Novartis. All other authors have declared no conflicts of interest.

e16097 Background: Inhibitors of the vascular endothelial growth factor (VEGF), its receptor (Ri) or mammalian target of rapamycin (mTORi) are components of systemic treatment in metastatic renal cell carcinoma (mRCC) and are applied in sequence. We compared the efficacy of VEGFRi and mTORi in 2nd line after failure of bevacizumab/interferon in a phase II trial. Methods: Key inclusion criteria were: measurable mRCC (all histologies), ECOG 0-1, IMDC risk: good or intermediate, adequate organ function. Tumor status was assessed in week 11 and q12 wks., thereafter. Measures of Health-related quality of life (HR-QoL) utilized FKSI-10 and was assessed in week 4, 10 and q12 wks., thereafter. 1st line consisted of bevacizumab 10mg/kg q2wks. + interferon 9*106 IE 3x/week (BEV/IFN). Upon progression or intolerance, patients were re-screened and randomized between VEGFRi (axitinib 5 mg BID, dose-escalation permitted; sunitinib 50 mg OD, 4-2 regimen) and everolimus (EVE) treatment (10 mg OD). Cross-over occurred at time of progression or intolerance. Improvement of 2nd line PFS-rate at 6 mo. from 50% to 65% was the primary endpoint. Secondary endpoints were PFS, total PFS, ORR, OS, safety and HR-QoL. Results: Between November 2012 and June 2015 a total of 22 of 100 patients were included and at that time stopped for poor accrual. 10 pts. (46%) were randomized to receive 2nd line treatment with everolimus (n = 5) or VEGFRi (n = 5). At study entry (2/10) 20% had nephrectomy. ECOG 0 was recorded in 20% (EVE) and 60% (VEGFRi), respectively. Objective response rate (ORR) to 1st line BEV/IFN was 20%. In 2nd line treatment all patients experienced adverse events (AE). Grade ≥3 AEs occurred in 2/5 (40%) (EVE) and 4/5 (80%) (VEGFRi) pts., respectively. SAEs occurred in 3/5 (60%) in each arm. ORR was 1/5 (20%) for axitinib and 0/5 (0%) for EVE. PFS rate at 180 days was 20% in each arm. Median PFS was 3.7 (EVE) and 2.2 mo. (VEGFRi) HR 1.0 (95%CI 0.26-3.85; p = 0.997). OS was comparable between arms HR 1.12 (95%CI 0.27-4.61; P = 0.872). 7 pts. crossed over to 3rd line treatment. Conclusions: The small number of pts. randomized to EVE or VEGFRi is a major limitation of our trial, but may mirror the current change of treatment reality. However, no significant difference was detected for the PFS rate at 6 mo., indicating the limited activity of EVE or VEGFRi in 2nd line treatment. Clinical trial information: NCT01731158.