Glycoprofiling of proteins as prostate cancer biomarkers: A multinational population study.

The glycoprofiling of two proteins, the free form of the prostate-specific antigen (fPSA) and zinc-α-2-glycoprotein (ZA2G), was assessed to determine their suitability as prostate cancer (PCa) biomarkers. The glycoprofiling of proteins was performed by analysing changes in the glycan composition on fPSA and ZA2G using lectins (proteins that recognise glycans, i.e. complex carbohydrates). The specific glycoprofiling of the proteins was performed using magnetic beads (MBs) modified with horseradish peroxidase (HRP) and antibodies that selectively enriched fPSA or ZA2G from human serum samples. Subsequently, the antibody-captured glycoproteins were incubated on lectin-coated ELISA plates. In addition, a novel glycoprotein standard (GPS) was used to normalise the assay. The glycoprofiling of fPSA and ZA2G was performed in human serum samples obtained from men undergoing a prostate biopsy after an elevated serum PSA, and prostate cancer patients with or without prior therapy. The results are presented in the form of an ROC (Receiver Operating Curve). A DCA (Decision Curve Analysis) to evaluate the clinical performance and net benefit of fPSA glycan-based biomarkers was also performed. While the glycoprofiling of ZA2G showed little promise as a potential PCa biomarker, the glycoprofiling of fPSA would appear to have significant clinical potential. Hence, the GIA (Glycobiopsy ImmunoAssay) test integrates the glycoprofiling of fPSA (i.e. two glycan forms of fPSA). The GIA test could be used for early diagnoses of PCa (AUC = 0.83; n = 559 samples) with a potential for use in therapy-monitoring (AUC = 0.90; n = 176 samples). Moreover, the analysis of a subset of serum samples (n = 215) revealed that the GIA test (AUC = 0.81) outperformed the PHI (Prostate Health Index) test (AUC = 0.69) in discriminating between men with prostate cancer and those with benign serum PSA elevation.

Real-World Evidence of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: An Austrian Multicenter Study.

INTRODUCTION: Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel), thus changing treatment strategies in metastatic hormonesensitive prostate cancer (mHSPC). PATIENTS AND METHODS: We conducted the first real-world analysis comprising 97 mHSPC patients from 16 Austrian medical centers, among them 79.4% of patients received abiraterone and 17.5% darolutamide treatment. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney U test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). RESULTS: Of 83.5% patients with synchronous and 16.5% with metachronous disease were included. 83.5% had high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37%, and 24.3% of patients, respectively. Importantly, a nonsimultaneous onset of chemotherapy and ARPI, performed in 44.3% of patients, was associated with significantly worse treatment response (P = .015, HR 0.245). Starting ARPI before chemotherapy was associated with significantly higher probability for progression (P = .023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3 to 5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. CONCLUSIONS: Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should be administered simultaneously, however if not possible, chemotherapy should be started first.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study.

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Real-world Outcomes and Predictive Biomarkers for 177Lutetium Prostate-specific Membrane Antigen Ligand Treatment in Metastatic Castration-resistant Prostate Cancer: A European Association of Urology Young Academic Urologists Prostate Cancer Working Group Multi-institutional Observational Study.

BACKGROUND: The European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers. OBJECTIVE: To assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models. RESULTS AND LIMITATIONS: A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046). CONCLUSIONS: 177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice. PATIENT SUMMARY: 177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.

Real-world comparison of Docetaxel versus new hormonal agents in combination with androgen-deprivation therapy in metastatic hormone-sensitive prostate cancer descrying PSA Nadir ≤ 0.05 ng/ml as marker for treatment response.

PROPOSE: Using Docetaxel chemotherapy or new hormonal agents (NHT) to intensify upfront systemic therapy resulted in improved survival rates compared to androgen deprivation monotherapy (ADT). Hence, combination therapies have become the new standard of care (SOC) in metastatic hormone-sensitive prostate cancer (mHSPC). However, head-to-head trails comparing different therapies as well as treatment-guiding biomarkers are still lacking. Thus, the aim of the present study was to compare clinical outcomes of Docetaxel versus NHT therapy in the real-world setting as well as to elaborate biomarkers predicting clinical outcome. METHODS: We retrospectively assessed overall-survival (OS), progression-free survival 1 and 2 (PFS1/2) and time to progression (TTP) in 42 patients treated by either ADT + NHT or ADT + Docetaxel. In addition, we investigated clinical prognostic biomarkers. RESULTS: Our survival analysis revealed 3-year OS of 89.4% in the NHT group compared to 82.4% in the Docetaxel group. 3-year PFS1 was 59.6% in the NHT group compared to 32.2% in the Docetaxel group and the TTP was 53.8% vs 32.2% (pOS = 0.189; pPFS1 = 0.082; pTTP = 0.055). In addition, castration-resistance occurred more often in the Docetaxel group (78.6% vs 25%, p = 0.004). Interestingly, a PSA-Nadir ≤ 0.05 ng/ml during therapy was associated with increased survival rates (p < 0.001) while PSA levels at primary diagnosis had no influence on therapy outcome. Furthermore, a thyroid-stimulating hormone (TSH) increase during therapy was associated with improved clinical outcome (p = 0.06). CONCLUSION: We observed a trend towards a higher benefit of NHT as first-line treatment compared to Docetaxel in men with mHSPC. Of note, a PSA-Nadir ≤ 0.05 ng/ml or a TSH-increase during therapy were predictors for therapy response.

Do we need repeated CT imaging in uncomplicated blunt renal injuries? Experiences of a high-volume urological trauma centre.

BACKGROUND: Current guidelines recommend repeat computed tomography (CT) imaging in high-grade blunt renal injury within 48-96 h, yet diagnostic value and clinical significance remain controversial. The aim of this work was to determine the possible gain of CT re-imaging in uncomplicated patients with blunt renal trauma at 48 h after injury, presenting one of the largest case series. METHODS: A retrospective database of patients admitted to our centre with isolated blunt renal trauma due to sporting injuries was analysed for a period of 20 years (2000-2020). We included only patients who underwent repeat imaging at 48 h after trauma irrespective of AAST renal injury grading (grade 1-5) and initial management. The primary outcome was intervention rates after CT imaging at 48 h in uncomplicated patients versus CT scan at the time of clinical symptoms. RESULTS: A total of 280 patients (mean age: 37.8 years; 244 (87.1%) male) with repeat CT after 48 h were included. 150 (53.6%) patients were classified as low-grade (grade 1-3) and 130 (46.4%) as high-grade (grade 4-5) trauma. Immediate intervention at trauma was necessary in 59 (21.1%) patients with high-grade injuries: minimally invasive therapy in 48 (81.4%) and open surgery in 11 (18.6%) patients, respectively. In only 16 (5.7%) cases, intervention was performed based on CT re-imaging at 48 h (low-grade vs. high-grade: 3.3% vs. 8.5%; p = 0.075). On the contrary, intervention rate due to clinical symptoms was 12.5% (n = 35). Onset of clinical progress was on average (range) 5.3 (1-17) days post trauma. High-grade trauma (odds ratio [OR]grade 4 vs. grade 3, 14.62; p < 0.001; ORgrade 5 vs. grade 3, 22.88, p = 0.004) and intervention performed at the day of trauma (OR 3.22; p = 0.014) were powerful predictors of occurrence of clinical progress. CONCLUSION: Our data suggest that routine CT imaging 48 h post trauma can be safely omitted for patients with low- and high-grade blunt renal injury as long as they remain clinically stable. Patients with high-grade renal injury have the highest risk for clinical progress; thus, close surveillance should be considered especially in this group.

Effects of cycling and rowing on serum concentrations of prostate-specific antigen: A randomized study of 101 male subjects.

OBJECTIVE: To determine the effects if cycling and rowing on serum prostate-specific antigen (PSA) levels. METHODS: Male volunteers (n = 101), aged 20-80 (mean, 49.9) years were randomized to exercise at the first or second study visit. They performed 1 h of either cycling or rowing on a stationary machine. To determine exercise-induced effects on the PSA level, serum total PSA (tPSA) and free PSA (fPSA) concentrations were evaluated before and after exercise and another sampling was performed at the second study visit. Pre-exercise and postexercise tPSA and fPSA concentrations were compared using the Wilcoxon matched-pairs test. The results were analyzed using the Mann-Whitney U-test. RESULTS: A significant (p < 0.001) average increase in tPSA after exercise (1.14 ± 1.11 ng/ml to 1.24 ± 1.26 ng/ml [mean, +8.8%]) was observed after both cycling and rowing, without significant differences between the sports (p = 0.54). The exercise-induced increase in PSA concentration affected participants aged ≥50 years (difference, 0.16 ± 0.37; p < 0.001), but not those aged <50 years (difference, 0.01 ± 0.06; p = 0.23). The effect size was clinically irrelevant in all except two outliers, in whom a distinct increase of PSA level by averages of 1.80 ng/ml (+55%) for tPSA and 1.25 ng/ml (+227%) for fPSA following cycling was observed. CONCLUSION: Rowing and cycling generally do not have a clinically relevant effect on PSA levels. However, outliers exist. Our findings do not support abstaining from exercise during the days approaching PSA sampling.

Optilume® drug-coated balloon dilation in complex female urethral stricture.

The treatment of female urethral stricture disease is in flux in terms of developing guidelines for surgical treatment. Urethral strictures in women are rare, but frequently result because of urethral instrumentation or surgery. Stricture sites vary from proximal, intrasphincteric, distal or at the meatus. Stricture formation after previous urethral surgery may pose a special challenge. We describe the first Optilume® urethral drug-coated balloon dilation for female urethral stricture disease involving the sphincter. After six months follow-up the patient remains stricture free with full continence and complete bladder emptying.

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec (p = 0.008) and Jan-Mar (p < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer.

Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic ParsortixTM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.

Comparison of Early Imaging and Imaging 60 min Post-Injection after Forced Diuresis with Furosemide in the Assessment of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT.

BACKGROUND: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min post-injection (p.i.) in the detection of LR in patients with biochemical recurrence (BR) of prostate carcinoma. MATERIALS AND METHODS: 190 image sets of patients with BR in PCa who underwent 68Ga-PSMA-11 PET/CT were assessed retrospectively (median prostate specific antigen (PSA) value, 0.70 ng/mL (range, 0.1-105.6 ng/mL)). Patients received an early static scan of the pelvic area (median, 248 s p.i. (range, 56-923 s)) and a whole-body scan 60 min p.i. (median, 64 min p.i. (range, 45-100 min)) with intravenous administration of 20 mg furosemide i.v. at the time of tracer application, followed by intravenous hydration with 500 mL of sodium chloride (NaCl 0.9%). Assessment was based on visual analysis and calculation of the maximum standardized uptake value (SUVmax) of the pathologic lesions present in the prostate fossa found in the early PET imaging and 60 min PET scans. The scans were characterized as negative, positive, or equivocal. The results were compared, and the combination of early and 60 min p.i. imaging was evaluated. RESULTS: Image assessment resulted in 30 (15.8%) positive, 17 (8.9%) equivocal, and 143 (75.3%) negative findings in early scans, and 28 (14.7%) positive, 25 (13.2%) equivocal, and 137 (72.1%) negative findings of LR in 60 min p.i. images. For combined image analysis, 33 (17.4%) cases were positive and 20 (10.5%) were equivocal. There was no statistical significance between the number of positive (p = 0.815), negative (p = 0.327), and equivocal (p = 0.152) findings. Furthermore, the combination of both scans showed no statistically significant differences for the positive and negative findings (p = 0.063). The median SUVmax was 4.9 (range, 2.0-55.2) for positive lesions in the early scans and 8.0 (range, 2.1-139.9) in the scans 60 min p.i. The median SUVmax for bladder activity was 2.5 (range, 0.9-12.2) in the early scans and 8.2 (range, 1.8-27.6) in the scans 60 min p.i. CONCLUSION: Early static imaging additional to 68Ga-PSMA-11 PET images acquired 60 min p.i. has limited value in patients prepared with furosemide and hydration, and showed no statistically significant change in the detection rate (DR) of LR and the number of equivocal findings. Based on our results, in departments following a protocol with forced diuresis, including furosemide, additional early static imaging cannot be routinely recommended for the assessment of BR in PCa patients.

A presumed extragonadal germ cell tumor that turned out to be a gastric cancer-a case report.

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (ß-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and ß-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.

The "COVID-19 Pandemic Gap" and Its Influence on Oncologic Outcomes of Bladder Cancer.

Coronavirus-19 (COVID-19)-induced effects on deferred diagnosis and treatment of bladder cancer (BC) patients are currently not clarified. The aim of this study was to evaluate outcomes of the COVID-19 pandemic by considering its effects on tumor stage and grade, and to create feasible clinical triage decisions. A retrospective single-center analysis of all patients who underwent diagnostic and surgical procedures due to BC, during January 2019 and December 2020, was performed. Due to COVID-19 lockdowns, significantly fewer (diagnostic and therapeutic) endoscopic procedures were performed in the first 6 months of 2020 compared to 2019 (p = 0.002). In patients with a primary diagnosis of BC, a significant increase of high-grade tumors (p < 0.001), as well as advanced tumor stages (p = 0.014), were noticed during 2020 in comparison to 2019. On the contrary, patients with recurrent BC undergoing risk-adapted surveillance, depending on previous tumor histology, showed no adverse outcomes regarding tumor stage and grade when comparing the pre COVID-19 era with 2020. Thus, more awareness in clinical urologic practice is mandatory to avoid adverse consequences, with increased rates of advanced and aggressive tumors in patients with primary BC. In recurrent BC, an individual risk stratification in order to avoid worse outcomes during the COVID-19 pandemic seems to be justified.

Sex-specific hormone changes during immunotherapy and its influence on survival in metastatic renal cell carcinoma.

Renal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor, being an ideal candidate for checkpoint blockade-based immunotherapy. Accordingly, checkpoint inhibitors have demonstrated clinical efficacy in patients with metastatic RCC (mRCC). Sex-specific differences in cancer immunotherapy may be explained by the interaction of sex hormone signaling, genetic and environmental factors, affecting the innate and adaptive immune response in men and women in different ways. The aim of this prospective study was to monitor for the first time changes in sex hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio and 17-ß-estradiol (E2) in 22 mRCC patients (12 male and 10 female) receiving nivolumab therapy. In contrast to female patients, male patients showed a significant increase in E2 (p = 0.006) and LH/FSH ratio (p = 0.013) from the beginning of nivolumab therapy to week 12 of follow-up. Moreover, survival analysis revealed a significant negative association between LH/FSH ratio and progression-free survival (PFS) (p = 0.022) as well as between therapy response (p = 0.009) in males compared to females at interim evaluation (week 6/8). Our findings may therefore be the first reference to sex hormone changes during immunotherapy.

Early Injection of Furosemide Increases Detection Rate of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT.

The aim of this study was twofold. First, we aimed to assess the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of 68Ga-PSMA-11 before it binds to the PSMA receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Methods: In a retrospective analysis, 2 different groups with 220 prostate cancer patients each, referred for 68Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients in group 1 (median prostate-specific antigen, 1.30 ng/mL) received no preparation before imaging, whereas patients in group 2 (median prostate-specific antigen, 0.82 ng/mL) were injected with 20 mg of furosemide and 500 mL of sodium chloride (NaCl 0.9%) immediately after tracer injection. The presence of local recurrence was assessed visually. In addition, the intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide than in patients without preparation: 56 cases (25.5%) versus 38 cases (17.3%), respectively (P = 0.048). Median maximum SUVs (SUVmax) of organs with physiologic uptake of 68Ga-PSMA-11 in groups 1 and 2 were urinary bladder (63.0 vs. 8.9), kidney (55.6 vs. 54.5), liver (9.9 vs. 9.4), spleen (11.2 vs. 11.9), small bowel (16.2 vs. 17.1), parotid gland (19.2 vs. 19.6), lacrimal gland (8.9 vs. 10.9), blood-pool activity (2.2 vs. 2.3), muscle (1.0 vs. 1.1), and bone (1.6 vs. 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg of furosemide at the time point of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-PSMA-11 PET/CT. As intensity of 68Ga-PSMA-11 uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of 68Ga-PSMA-11 seems unlikely.

Lynch Syndrome: Its Impact on Urothelial Carcinoma.

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.

Impact of forced diuresis with furosemide and hydration on the halo artefact and intensity of tracer accumulation in the urinary bladder and kidneys on [68Ga]Ga-PSMA-11-PET/CT in the evaluation of prostate cancer patients.

PURPOSE: to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [68Ga]Ga-PSMA-11-PET/CT scans. MATERIALS AND METHODS: Comparison of four groups with 50 patients each, receiving different preparation prior to [68Ga]Ga-PSMA-11-PET/CT. Group one, no preparation. Group two, 500 ml sodium chloride administered immediately after tracer injection. Group three, 500 ml sodium chloride and injection of 20 mg furosemide immediately after tracer administration. Group four, 500 ml sodium chloride and injection of 40 mg furosemide immediately after tracer injection. Images were judged visually whether halo artefact was present; semiquantitative measurements were performed with standardised uptake value (SUV). RESULTS: Halo artefact of the urinary bladder was present in twelve patients without preparation, in eight patients receiving only sodium chloride, in one patient injected with 20 mg furosemide/sodium chloride and in two patients receiving 40 mg furosemide/sodium chloride, showing a median SUVmean in the bladder of 45.8, 14.4, 4.6 and 5.8, respectively. Differences between patient group without preparation and the two groups with furosemide/sodium chloride were statistically significant. Patient groups receiving 20 mg furosemide and 40 mg furosemide did not differ significantly. Renal halo artefacts were observed in 15 patients of group one, in ten patients of group two, in 14 patients of group three and in 14 patients of group four, with corresponding median SUVmean values of 33.9, 32.0, 37.8 and 30.4 (no statistically significant differences). CONCLUSION: Performing [68Ga]Ga-PSMA-11-PET/CT, intravenous injection of 20-mg furosemide and 500-ml sodium chloride significantly reduces the number of bladder halo artefacts and intensity of tracer accumulation in the urinary bladder. A total of 40 mg furosemide does not further improve results.

Organ-Sparing Surgery in Testicular Tumor: Is This the Right Approach for Lesions ≤ 20 mm?

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (£20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen section examination (FSE) for the past 15 years at our institution. Benign and malignant cases were compared, focusing on preoperative and postoperative lesion sizes. Results: Eighty-nine patients were enrolled in this retrospective study. Ten (11.2%) of them were treated for synchronous bilateral tumors. Sixty-seven (67.7%) of ninety-nine lesions were benign, confirming a high concordance rate (98%) between FSE and final histology. Patients with benign tumors were significantly older than patients with malignant tumors (p = 0.026), and benign tumors were detected more frequently during urologic work-up of hormone disorders (p = 0.001). Preoperative tumor size was a strong predictor of malignancy (area under the curve (AUC) = 0.726; p < 0.001). According to the Youden index, the best cutoff to predict tumor dignity was 13.5 mm, resulting in a sensitivity and specificity of 53% and 85%, respectively. No cases of local recurrence or distant metastasis were confirmed after a median follow-up of 42 months. Conclusion: Our findings are consistent with previous reports, supporting an OSS approach in small testicular tumors whenever possible. Most tumors ≤ 20 mm were benign, and in the case of malignancy, OSS with FSE and consecutive orchiectomy is oncologically safe due to the high concordance rate of FSE and final histology, thus preventing a two-stage procedure.

Urethro-cavernosal-spongiosal fistula after intralesional mitomycin C for recurrent urethral stricture disease.

Intralesional mitomycin C after direct visual internal urethrotomy for recurrent urethral stricture disease in patients suboptimal for open urethroplasty is an established option. We report a case of urethro-cavernosal-spongiosal fistula after intralesional mitomycin C into an area of previous dorsal inlay urethroplasty. The patient presented with pus draining from the urethral meatus ten days after treatment. Sterile abscesses developed within the corporal and spongious bodies, draining freely into the urethra. Complete spontaneous healing followed short-term transurethral catheterization and antibiotic prophylaxis.