Immunotherapy and Sonpavde score validation in advanced upper tract urothelial carcinoma: a retrospective study by the Italian Network for Research in Urologic-Oncology (Meet-URO group).

Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. A total of 78 UTUC patients were enrolled.

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study).

Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy.

Incidence and Clinical Impact of Inflammatory Fluorodeoxyglucose Positron Emission Tomography Uptake After Neoadjuvant Pembrolizumab in Patients with Organ-confined Bladder Cancer Undergoing Radical Cystectomy.

Background: Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by [F] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan, in patients receiving immune-checkpoint inhibitors (ICIs) are lacking. We relied on the population of patients enrolled in the PURE-01 study to evaluate such changes.

Objective: To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab.

[18F]Fluoro-Deoxy-Glucose positron emission tomography to evaluate lymph node involvement in patients with muscle-invasive bladder cancer receiving neoadjuvant pembrolizumab.

Background: Data regarding the role of positron emission tomography/computed tomography (PET/CT) to stage lymph nodes in patients receiving neoadjuvant immunotherapy before radical cystectomy are lacking. The aim of this study is to evaluate the role of PET/CT to predict the pathologic lymph node involvement (LNI) in patients with MIBC receiving neoadjuvant pembrolizumab within the PURE-01 trial (NCT02736266).

Material And Methods: Three courses of pembrolizumab were administered before radical cystectomy and extended pelvic lymph node dissection in clinical T2-4aN0M0 MIBC based on contrast-enhanced CT scan.

Prognostic Role of Early Interim Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced Seminoma Undergoing Standard Treatment.

Background: Patients with advanced seminoma have an exceedingly favorable prognosis. Studies aiming to reduce the total treatment burden and side effects in patients with well-defined disease and very good prognosis are warranted.

Patients And Methods: In a prospective observational study, patients with advanced stage seminoma were treated with bleomycin, etoposide, and cisplatin (BEP) or EP according to guidelines.

Predicting the Pathologic Complete Response After Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer.

Background: In the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers.

Methods: In an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)-combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples.

Can Patients with Muscle-invasive Bladder Cancer and Fibroblast Growth Factor Receptor-3 Alterations Still Be Considered for Neoadjuvant Pembrolizumab? A Comprehensive Assessment from the Updated Results of the PURE-01 Study.

In the PURE-01 study, patients with muscle-invasive bladder cancer (MIBC) who achieved a pathological complete response (CR; ypT0N0) had tumor features suggesting that pre-existing immunity may promote response. We focused on fibroblast growth factor receptor-3 (FGFR3) genomic alterations (GAs) as potential tumor resistance features. The primary endpoint of our study was CR.

Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer.

Background: The PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC).

Objective: To evaluate the ability of molecular signatures to predict the pathological complete response (CR: ypT0N0) and progression-free survival (PFS) after pembrolizumab and RC.

Design, Setting, And Participants: We analyzed the expression data from patients with T2-4aN0M0 MIBC enrolled in the PURE-01 study (N=84) and from patients of a retrospective multicenter cohort treated with cisplatin-based neoadjuvant chemotherapy (NAC; N=140).

Multiparametric Magnetic Resonance Imaging as a Noninvasive Assessment of Tumor Response to Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer: Preliminary Findings from the PURE-01 Study.

Background: In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients.

Objective: To evaluate the association between bladder multiparametric magnetic resonance imaging (mpMRI) findings after pembrolizumab and the pathological complete response (CR; pT0).

Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies.

Background: Patients with predominant variant histology (VH) of bladder tumors, defined as involving >50 % of the tumor specimens, are typically excluded from clinical trials, and for these patients, the efficacy of standard chemotherapy is limited.

Objective: To evaluate the activity of preoperative pembrolizumab in patients with muscle-invasive bladder carcinoma (MIBC) and VH, enrolled in PURE-01 study (NCT02736266).

Design, Setting, And Participants: In the open-label, single-arm, phase 2 PURE-01 study, three courses of 200 mg pembrolizumab preceding radical cystectomy (RC) were administered in T2-4aN0M0 MIBC patients.

Erdafitinib for the treatment of urothelial cancer.

: Fibroblast growth-factor receptor (FGFR) inhibition is a promising strategy of treatment in urothelial cancer (UC). mutations or fusions (mut/fus) are common in luminal-1 UC subtype, which exhibits poor responses to immunotherapy. Erdafitinib is a potent and selective pan-FGFR tyrosine kinase inhibitor.

Single-Agent Gemcitabine vs. Carboplatin-Gemcitabine in Advanced Breast Cancer: A Retrospective Comparison of Efficacy and Safety Profiles.

Background: Single-agent gemcitabine is a moderately effective compound in metastatic breast cancer (mBC) treatment. Carboplatin is frequently used in addition to gemcitabine to improve tumor responses, but with an unclear effect on survival outcomes. In this study we evaluated the antitumor efficacy and safety profiles of gemcitabine and carboplatin-gemcitabine in mBC patients.

Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study.

Purpose: To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used.

Patients And Methods: In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c)T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC.

A Combination of Cisplatin and 5-Fluorouracil With a Taxane in Patients Who Underwent Lymph Node Dissection for Nodal Metastases From Squamous Cell Carcinoma of the Penis: Treatment Outcome and Survival Analyses in Neoadjuvant and Adjuvant Settings.

Background: The role of chemotherapy in nodal metastases from penile squamous cell carcinoma is not defined. We evaluated the efficacy of a combination of T-PF (a taxane, cisplatin, and 5-fluorouracil) in neoadjuvant and adjuvant settings.

Patients And Methods: Since June of 2004, T-PF was administered to stage N2 to 3 patients.

Quality of life and pain control following laparoscopic retroperitoneal lymph node dissection in early-stage nonseminoma.

Aims And Background: To evaluate postoperative pain (PoP) and quality of life (QoL) in patients undergoing open (O-) or laparoscopic (L-) retroperitoneal lymph node dissection (RPLND) for clinical stage I (CS I) and normal markers CS IIA nonseminomatous germ cell tumors.

Methods: Since March 2010, a prospective nonrandomized trial evaluated dynamic and rest (R) numeric pain scale (NPS) following patient-controlled analgesia and baseline (T0), 3-month (T3), and 6-month (T6) QoL status assessed by Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and the Italian-validated Functional Assessment of Chronic Illness Therapy (FACT-T-SG) at T6. Secondary endpoints included length of hospital stay (LHS), interval to recovery (ItR), complications, and oncologic outcomes.

Clinical Outcomes of Metastatic Poor Prognosis Germ Cell Tumors: Current Perspective From a Referral Center.

Background: Survival estimates with first-line treatment for patients with metastatic poor prognosis germ cell tumors (GCT) are still suboptimal in the literature. We conducted a retrospective study to evaluate the outcome of patients referred to our tertiary cancer center.

Patients And Methods: A retrospective analysis was conducted on patients who received at least first-line chemotherapy at our center.

Clinical outcome in testicular sex cord stromal tumors: testis sparing vs. radical orchiectomy and management of advanced disease.

Objective: To assess the clinical outcome of testicular sex cord stromal tumors (TSCST) according to management and stage.

Patients And Methods: Clinical and pathologic features, stage, and treatment of patients with TSCST were retrieved from our database. The Kaplan-Meier method estimated the relapse-free survival and cancer-specific survival.

High-dose chemotherapy for germ cell tumors: do we have a model?

Introduction: Since the late nineties, the intensification of chemotherapy doses with hematopoietic stem cell rescue held promise for patients with advanced and poor prognosis germ cell tumors (GCTs). High-dose chemotherapy (HDCT) has, nowadays, a recognized indication in the salvage setting of advanced GCTs and is steadily utilized worldwide.

Areas Covered: We evaluated the available data with the use of HDCT in these patients.

Immunohistochemistry to enhance prognostic allocation and guide decision-making of patients with advanced urothelial cancer receiving first-line chemotherapy.

Background: Knowledge of the expression of molecular drivers and potentially druggable targets might enhance prognostic classification of M UC.

Materials And Methods: We analyzed archival tissue from patients with UC who underwent first-line chemotherapy for locally advanced (LA) and M disease between the years 2000 and 2013. The following biomarkers were evaluated using IHC: excision repair cross complementation (ERCC) group 1 (ERCC1), epidermal growth factor receptor (EGFR), HER2, VEGFR-3, PDGFRα, p53, and p63.

Etoposide, Methotrexate, and Dactinomycin Alternating With Cyclophosphamide and Vincristine (EMACO) for Male Patients With HCG-expressing, Chemoresistant Germ Cell Tumors.

Objectives: To retrospectively analyze the efficacy and safety results of the combination of methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO) regimen for patients with human chorionic gonadotropin (HCG)-producing germ cell tumors and who had failed multiple courses of chemotherapy.

Methods: Patients who had failed at least 2 regimens received methotrexate 100 mg/m, followed by methotrexate 200 mg/m over 12 hours day 1, etoposide 100 mg/m and dactinomycin 0.5 mg days 1 and 2, folinic acid 25 mg orally every 6 hours days 2 and 3, alternating with cyclophosphamide 600 mg/m plus vincristine 1 mg/m day 8, every 21 days.

A prognostic model including pre- and postsurgical variables to enhance risk stratification of primary mediastinal nonseminomatous germ cell tumors: the 27-year experience of a referral center.

Background: Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis.

Patients And Methods: Between the years 1985 and 2012, 86 patients with PMGCT were treated at our center.

Interim fluorine-18 fluorodeoxyglucose positron emission tomography for early metabolic assessment of therapeutic response to chemotherapy for metastatic transitional cell carcinoma.

Background: The prognostic impact of early metabolic response by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) after 2 cycles of first-line chemotherapy is still unrecognized in metastatic transitional cell carcinoma (TCC).

Patients And Methods: Patients with metastatic TCC receiving the modified combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), according to institutional protocol, underwent computed tomography (CT) and FDG-PET imaging at baseline, a restaging with PET imaging after 2 cycles only (PET2), and a CT (± FDG-PET) scan at the end of treatment and during follow-up. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method; univariate (UVA) and multivariate (MVA) Cox models were fitted.

Long-term efficacy and safety outcomes of modified (simplified) MVAC (methotrexate/vinblastine/doxorubicin/cisplatin) as frontline therapy for unresectable or metastatic urothelial cancer.

Background: The classic MVAC (methotrexate/vinblastine/doxorubicin/cisplatin) regimen was the first recognized option for untreated patients with locally advanced or metastatic urothelial cancer (UC). Modifying MVAC by reducing side effects may have the potential to improve efficacy.

Patients And Methods: Changes to classic MVAC were provided at the authors' institution: (1) deletion of day 22 and administration of 25 mg/m(2) cisplatin on days 2 to 5 (modified [m]MVAC); (2) deletion of day 22 only (simplified [s]MVAC1); and (3) deletion of days 15 and 22 in a 3-week schedule (sMVAC2).