Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately ...15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.
We evaluated possible factors predicting testicular cancer in patients undergoing testis sparing surgery.
We retrospectively analyzed the records of all patients who underwent testis sparing surgery ...for a small testicular mass at a total of 5 centers. All patients with 1 solitary lesion 2 cm or less on preoperative ultrasound were enrolled in the study. Testis sparing surgery consisted of tumor enucleation for frozen section examination. Immediate radical orchiectomy was performed in all cases of malignancy at frozen section examination but otherwise the testes were spared. Univariate and multivariate analysis were performed and ROC curves were produced to evaluate preoperative factors predicting testicular cancer.
Overall 147 patients were included in the study. No patient had elevated serum tumor markers. Overall 21 of the 147 men (14%) presented with testicular cancer. On multivariate analysis the preoperative ultrasound diameter of the lesion was a predictor of malignancy (OR 6.62, 95% CI 2.26-19.39, p=0.01). On ROC analysis lesion diameter had an AUC of 0.75 (95% CI 0.63-0.86, p=0.01) to predict testicular cancer. At the best cutoff of 0.85 the diameter of the lesion had 81% sensitivity, 58% specificity, 24% positive predictive value and 95% negative predictive value.
Our study confirms that small testicular masses are often benign and do not always require radical orchiectomy. Preoperative ultrasound can assess lesion size and the smaller the nodule, the less likely that it is malignant. Therefore, we suggest a stepwise approach to small testicular masses, including tumorectomy, frozen section examination and radical orchiectomy or testis sparing surgery according to frozen section examination results.
Purpose
The conventional imaging flowchart for prostate cancer (PCa) staging may fail in correctly detecting lymph node metastases (LNM). Pelvic lymph node dissection (PLND) represents the only ...reliable method, although invasive. A new amino acid PET compound,
18
F-fluciclovine, was recently authorized in suspected PCa recurrence but not yet included in the standard staging work-up of primary PCa. A prospective monocentric study was designed to evaluate
18
F-fluciclovine PET/CT diagnostic performance for preoperative LN staging in primary high-risk PCa.
Methods
Consecutive patients (pts) with biopsy-proven PCa, standard staging (including
11
Ccholine PET/CT), eligible for PLND, were enrolled to undergo an investigational
18
F-fluciclovine PET/CT. Nodal uptake higher than surrounding background was reported by at least two readers (blinded to
11
Ccholine) using a visual 5-point scale (1–2 probably negative; 4–5 probably positive; 3 equivocal); SUVmax, target-to-background (aorta—A; bone marrow—BM) ratios (TBRs), were also calculated. PET results were validated with PLND.
18
F-fluciclovine PET/CT performance using visual score and semi-quantitative indexes was analyzed both per patient and per LN anatomical region, compared to conventional
11
Ccholine and clinical predictive factors (to note that diagnostic performance of
18
F-fluciclovine was explored for LNM but not examined for intrapelvic or extrapelvic M1 lesions).
Results
Overall, 94 pts underwent
18
F-fluciclovine PET/CT; 72/94 (77%) high-risk pts were included in the final analyses (22 pts excluded: 8 limited PLND; 3 intermediate-risk; 2 treated with radiotherapy; 4 found to be M1; 5 neoadjuvant hormonal therapy). Median LNM risk by Briganti nomogram was 19%. LNM confirmed on histology was 25% (18/72 pts). Overall, 1671 LN were retrieved; 45/1671 (3%) LNM detected. Per pt, median no. of removed LN was 22 (mean 23 ± 10; range 8–51), of LNM was 2 (mean 3 ± 2; range 1–10). Median LNM size was 5 mm (mean 5 ± 2.5; range 2–10). On patient-based analyses (n = 72), diagnostic performance for LNM resulted significant with
18
F-fluciclovine (AUC 0.66,
p
0.04; 50% sensitivity, 81% specificity, 47% PPV, 83% NPV, 74% accuracy), but not with
11
Ccholine (AUC 0.60,
p
0.2; 50%, 70%, 36%, 81%, and 65% respectively). Briganti nomogram (OR = 1.03,
p
= 0.04) and
18
F-fluciclovine visual score (≥ 4) (OR = 4.27,
p
= 0.02) resulted independent predictors of LNM at multivariable analyses. On region-based semi-quantitative analyses (n = 576), PET/CT performed better using TBR parameters (TBR-A similar to TBR-BM; TBR-A fluciclovine AUC 0.61,
p
0.35, vs choline AUC 0.57
p
0.54; TBR-BM fluciclovine AUC 0.61,
p
0.36, vs choline AUC 0.58,
p
0.52) rather than using absolute LN SUVmax (fluciclovine AUC 0.51,
p
0.91, vs choline AUC 0.51,
p
0.94). However, in all cases, diagnostic performance was not statistically significant for LNM detection, although slightly in favor of the experimental tracer
18
F-fluciclovine for each parameter. On the contrary, visual interpretation significantly outperformed PET semi-quantitative parameters (choline and fluciclovine: AUC 0.65 and 0.64 respectively;
p
0.03) and represents an independent predictive factor of LNM with both tracers, in particular
18
F-fluciclovine (OR = 8.70,
p
0.002, vs OR = 3.98,
p
= 0.03).
Conclusion
In high-risk primary PCa,
18
F-fluciclovine demonstrates some advantages compared with
11
Ccholine but sensitivity for metastatic LN detection is still inadequate compared to PLND. Visual (combined morphological and functional), compared to semi-quantitative assessment, is promising but relies mainly on readers’ experience rather than on unquestionable LN avidity.
Trial registration
EudraCT number: 2014–003,165-15
Purpose
To determine the clinical, pathological, and radiological features, including the Vesical Imaging-Reporting and Data System (VI-RADS) score, independently correlating with muscle-invasive ...bladder cancer (BCa), in a multicentric national setting.
Method and Materials
Patients with BCa suspicion were offered magnetic resonance imaging (MRI) before trans-urethral resection of bladder tumor (TURBT). According to VI-RADS, a cutoff of ≥ 3 or ≥ 4 was assumed to define muscle-invasive bladder cancer (MIBC). Trans-urethral resection of the tumor (TURBT) and/or cystectomy reports were compared with preoperative VI-RADS scores to assess accuracy of MRI for discriminating between non-muscle-invasive versus MIBC. Performance was assessed by ROC curve analysis. Two univariable and multivariable logistic regression models were implemented including clinical, pathological, radiological data, and VI-RADS categories to determine the variables with an independent effect on MIBC.
Results
A final cohort of 139 patients was enrolled (median age 70 IQR: 64, 76.5). MRI showed sensitivity, specificity, PPV, NPV, and accuracy for MIBC diagnosis ranging from 83–93%, 80–92%, 67–81%, 93–96%, and 84–89% for the more experienced readers. The area under the curve (AUC) was 0.95 (0.91–0.99). In the multivariable logistic regression model, the VI-RADS score, using both a cutoff of 3 and 4 (
P
< .0001), hematuria (
P
= .007), tumor size (
P
= .013), and concomitant hydronephrosis (
P
= .027) were the variables correlating with a bladder cancer staged as ≥ T2. The inter-reader agreement was substantial (
k
= 0.814).
Conclusions
VI-RADS assessment scoring proved to be an independent predictor of muscle-invasiveness, which might implicate a shift toward a more aggressive selection approach of patients’ at high risk of MIBC, according to a novel proposed predictive pathway.
We aimed to review the current state‐of‐the‐art imaging methods used for primary and secondary staging of prostate cancer, mainly focusing on multiparametric magnetic resonance imaging and ...positron‐emission tomography/computed tomography with new radiotracers. An expert panel of urologists, radiologists and nuclear medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE search for prospective, retrospective original research, systematic review, meta‐analyses and clinical guidelines for local and systemic staging of the primary tumor and recurrence disease after treatment. Despite magnetic resonance imaging having low sensitivity for microscopic extracapsular extension, it is now a mainstay of prostate cancer diagnosis and local staging, and is becoming a crucial tool in treatment planning. Cross‐sectional imaging for nodal staging, such as computed tomography and magnetic resonance imaging, is clinically useless even in high‐risk patients, but is still suggested by current clinical guidelines. Positron‐emission tomography/computed tomography with newer tracers has some advantage over conventional images, but is not cost‐effective. Bone scan and computed tomography are often useless in early biochemical relapse, when salvage treatments are potentially curative. New imaging modalities, such as prostate‐specific membrane antigen positron‐emission tomography/computed tomography and whole‐body magnetic resonance imaging, are showing promising results for early local and systemic detection. Newer imaging techniques, such as multiparametric magnetic resonance imaging, whole‐body magnetic resonance imaging and positron‐emission tomography/computed tomography with prostate‐specific membrane antigen, have the potential to fill the historical limitations of conventional imaging methods in some clinical situations of primary and secondary staging of prostate cancer.
(1) Objectives: To describe the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin–tazobactam or meropenem monotherapy and ...microbiological outcome in a case series of urological patients with documented Gram-negative infections. (2) Methods: Patients admitted to the urology ward who were treated with CI piperacillin–tazobactam or meropenem monotherapy for documented Gram-negative infections and underwent real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program from June 2021 to May 2023 were retrospectively retrieved. Average steady-state (Css) piperacillin–tazobactam and meropenem concentrations were determined, and the free fractions (fCss) were calculated. Optimal PK/PD target attainments were defined as an fCss/MIC ratio >4 for CI meropenem and an fCss/MIC ratio of piperacillin >4 coupled with an fCss/CT ratio for tazobactam >1 for piperacillin–tazobactam (joint PK/PD target). The relationship between beta-lactam PK/PD targets and microbiological outcome was explored. (3) Results: Sixteen urologic patients with documented Gram-negative infections (62.5% complicated urinary tract infections (cUTI)) had 30 TDM-guided ECPAs. At first TDM assessment, beta-lactam dosing adjustments were recommended in 11 out of 16 cases (68.75%, of which 62.5% decreases and 6.25% increases). Overall, beta-lactam dosing adjustments were recommended in 14 out of 30 ECPAs (46.6%). Beta-lactam PK/PD target attainments were optimal in 100.0% of cases. Microbiological failure occurred in two patients, both developing beta-lactam resistance. (4) Conclusion: A TDM-guided ECPA program may allow for optimizing beta-lactam treatment in urologic patients with documented Gram-negative infections, ensuring microbiological eradication in most cases.
Purpose
To perform an external validation of a recently published nomogram aimed to predict positive
68
Ga-PSMA-11 PET/CT in patients with biochemical recurrence (BCR) after radical prostatectomy ...(RP) by Rauscher et al. (Eur Urol 73(5):656–661,
2018
).
Methods
Overall, 413 PCa patients with BCR after RP (two consecutive PSA ≥ 0.2 ng/ml) and PSA value between 0.2 and 1 ng/ml were included. A multivariable logistic regression model was produced to assess the predictors of positive
68
Ga-PSMA-11 PET/CT results. The performance characteristics of the model were assessed by quantifying the predictive accuracy, according to model calibration. Yuden’s index was used to find the best nomogram’s cut-off. Finally, decision curve analysis (DCA) was implemented to quantify the nomogram’s clinical value.
Results
In the external cohort, the overall detection rate of
68
Ga-PSMA-11 PET/CT was 44% vs. 64.7% in the original population. At multivariate analysis, PSA at
68
Ga-PSMA-11 PET/CT (OR: 7.06,
p
< 0.001) and ongoing ADT at time of
68
Ga-PSMA-11 PET/CT (OR: 2.07,
p
= 0.03) were the only independent predictors of PET/CT positivity. The predictive accuracy of nomogram was suboptimal and comparable to that reported in the original model (64% vs. 67%, respectively). The calibration plot indicated suboptimal concordance. The best nomogram’s cut-off to predict positive
68
Ga-PSMA-11 PET/CT was 35% (AUC = 0.61). In DCA, the nomogram revealed clinical net benefit when the threshold probabilities of positive
68
Ga-PSMA-11 PET/CT is > 35%.
Conclusion
We assessed similar suboptimal predictive accuracies in the external cohort compared to the original one. PSA and ongoing ADT were confirmed as positive predictors, and the most informative nomogram cut-off resulted 35%.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and ...diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters.
We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated.
Forty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen's kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen's kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (
= 0.3) and PSMA-TL (
= 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (
= 0.04). Higher SUVmax was associated with membranous and combined VP expression (
= 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (
= 0.5,
= 0.5, and
= 0.9 respectively).
We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score.
Purpose
To assess the role of the multiparametric Magnetic Resonance Imaging (mpMRI) in predicting the cribriform pattern in both the peripheral and transition zones (PZ and TZ) clinically ...significant prostate cancers (csPCas).
Material and methods
We retrospectively evaluated 150 patients who underwent radical prostatectomy for csPCa and preoperative mpMRI. Patients with negative (
n
= 25) and positive (
n
= 125) mpMRI, stratified according to the presence of prevalent cribriform pattern (PCP, ≥ 50%) and non-PCP (< 50%) at specimen, were included. Difference between the two groups were evaluated. Multivariate logistic regression was used to identify predictors of PCP among mpMRI parameters. The receiver operating characteristic (ROC) analysis was performed to evaluate the area under the curve (AUC) of apparent diffusion coefficient (ADC) and ADC ratio in detecting lesions harboring PCP.
Results
Considering 135 positive lesions at the mpMRI, 30 (22.2%) and 105 (77.8%) harbored PCP and non-PCP PCa. The PCP lesions had more frequently nodular morphology (83.3% vs 62.9%;
p
= 0.04) and significantly lower mean ADC value (0.87 ± 0.16 vs 0.95 ± 0.18;
p
= 0.03) and ADC ratio (0.52 ± 0.09 vs 0.60 ± 0.14;
p
= 0.003) when compared with non-PCP lesions. At univariate and multivariate analyses, mean ADC and ADC ratio resulted as independent predictors of the presence of the PCP of the PZ tumors(OR: 0.025;
p
= 0.03 and OR: 0.001;
p
= 0.004, respectively). At the ROC analysis, the AUC of mean ADC and ADC ratio to predict the presence of PCP in patients with PZ suspicious lesion at the mpMRI were 0.69 (95% CI 0.56–0.81P,
p
= 0.003) and 0.72 (95% CI 0.62–0.82P,
p
= 0.001), respectively.
Conclusions
The mpMRI may correctly identify PCP tumors of the PZ and the mean ADC value and ADC ratio can predict the presence of the cribriform pattern in the PCa.
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