Real-World Outcomes and Molecular Profiling for Patients with Metastatic Castration-resistant Prostate Cancer with Lung Metastases: A Long-term Multicenter Experience.

Background And Objective: The prognostic impact of lung metastases (LuMs) in metastatic castration-resistant prostate cancer (mCRPC) remains poorly defined. Our aim was to evaluate the clinical and molecular characteristics of patients with mCRPC with LuMs and their outcomes.

Methods: This retrospective multicenter study included 930 patients with mCRPC across 13 centers in Italy.

Validation of a Combined Prognostic Score Using Plasma Tumor DNA and Clinical Features in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Taxanes.

Purpose: There is an urgent need of biomarkers to personalize metastatic castration-resistant prostate cancer (mCRPC) treatment. A new prognostic model described by our group combines molecular characteristics (ptDNA levels), metabolic features from PET-scans (metabolic tumor volume), clinical parameters (visceral metastases), and lab tests (lactate-dehydrogenase levels) in abiraterone or enzalutamide-treated patients. This study aims to validate the score on mCRPC patients undergoing taxane treatment.

Changing metastatic patterns associate with dynamics of circulating tumor DNA in metastatic castration-resistant prostate cancer.

Background: Circulating tumor DNA (ctDNA) acts as an early biomarker of the efficacy of androgen receptor signaling inhibitor (ARSI) therapy. In this study, we aimed to reveal if ctDNA can supplement imaging to better predict metastasis burden and radiographic progression disease (PD) in metastatic castration-resistant prostate cancer (mCRPC).

Methods: Targeted next-generation sequencing was performed to assess ctDNA fraction.

An evaluation of talazoparib plus enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

Introduction: Prostate cancer (PCa) is the second most common cancer diagnosis among men worldwide, with poor prognosis in its advanced stage. Treatment strategies have evolved, including the use of androgen receptor pathway inhibitors (ARPIs) and poly (ADP-ribose) polymerase inhibitors (PARPis).

Areas Covered: This review evaluates the clinical efficacy, safety, and future potential of combining talazoparib, a potent PARPi, with enzalutamide, a strong androgen receptor (AR) antagonist.

Correlation of [Ga]Ga-PSMA PET/CT response and PSA decline in first-line enzalutamide for metastatic castration-resistant prostate cancer patients.

Purpose: to assess the utility of response monitoring to enzalutamide by using [Ga]Ga-PSMA PET in mCRPC patients treated with enzalutamide as first-line therapy.

Methods: patients underwent [Ga]Ga-PSMA PET less than 8 weeks before and 3 months after starting enzalutamide. On the basis of EAU/EANM criteria, patients were categorized as PSMA responders (PET-R) or PSMA non-responders (PET-NR), whilst, based on PSA, they were classified as biochemical responders (PSA-R) or non-responders (PSA-NR).

Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study.

Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown.

Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance.

Design Setting And Participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes.

Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care.

Background: Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC.

Methods: A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified.

Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors.

The outcome of metastatic testicular germ cell tumor patients has been dramatically improved by cisplatin-based chemotherapy combinations. However, up to 30% of patients with advanced disease relapse after first-line therapy and require salvage regimens, which include treatments with conventional-dose chemotherapy or high-dose chemotherapy with autologous stem cell transplantation. For these patients, prognosis estimation represents an essential step in the choice of medical treatment but still remains a complex challenge.

Impact of the time interval between primary or interval surgery and adjuvant chemotherapy in ovarian cancer patients.

Introduction: Primary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes.

Methods: We conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC.

Immunogenomic profiles associated with response to life-prolonging agents in prostate cancer.

Prostate cancer is the most commonly diagnosed cancer but the management of advanced prostate cancer remains a therapeutic challenge, despite the survival benefits imparted by several therapeutic discoveries targeting different molecular pathways. The mechanisms of resistance to androgen deprivation and tumour progression to lethal metastatic variants are often regulated by androgen receptor (AR) bypass mechanisms and/or neuroendocrine differentiation. Moreover, recent data also suggested the involvement of adaptive and innate infiltrated immune cells in prostate tumour progression.

The New Frontier of Immunotherapy: Chimeric Antigen Receptor T (CAR-T) Cell and Macrophage (CAR-M) Therapy against Breast Cancer.

Breast cancer represents one of the most common tumor histologies. To date, based on the specific histotype, different therapeutic strategies, including immunotherapies, capable of prolonging survival are used. More recently, the astonishing results that were obtained from CAR-T cell therapy in haematological neoplasms led to the application of this new therapeutic strategy in solid tumors as well.

Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors.

Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected.

Circulating inflammatory cells in patients with metastatic breast cancer: Implications for treatment.

Adaptive and innate immune cells play a crucial role as regulators of cancer development. Inflammatory cells in blood flow seem to be involved in pro-tumor activities and contribute to breast cancer progression. Circulating lymphocyte ratios such as the platelet-lymphocytes ratio (PLR), the monocyte-lymphocyte ratio (MLR) and the neutrophil-lymphocyte ratio (NLR) are new reproducible, routinely feasible and cheap biomarkers of immune response.

Inflammatory Biomarkers for Outcome Prediction in Patients With Metastatic Testicular Cancer.

Germ cell tumors are the most common malignant tumors in male young adults. Platinum-based chemotherapy has dramatically improved the outcome of metastatic germ cell tumor patients and overall cure rates now exceed 80%. The choice of medical treatment can be guided by the prognosis estimation which is an important step during the decision-making process.

Baseline Plasma Tumor DNA (ctDNA) Correlates with PSA Kinetics in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.

Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples.

Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel.

Background: Cabazitaxel improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel. In this prospective study, we evaluated the prognostic role of CTC gene expression on cabazitaxel-treated patients and its association with plasma androgen receptor (AR) copy number (CN).

Methods: Patients receiving cabazitaxel 20 or 25 mg/sqm for mCRPC were enrolled.

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications.

Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies.

Combining liquid biopsy and functional imaging analysis in metastatic castration-resistant prostate cancer helps predict treatment outcome.

Plasma tumour DNA (ptDNA) is a potential early noninvasive biomarker of treatment outcome in metastatic castration-resistant prostate cancer (mCRPC). Herein, we investigated whether pretreatment ptDNA levels reflect metabolic tumour burden in mCRPC and better predict treatment outcome in combination with functional imaging. Targeted next-generation sequencing was performed to estimate the ptDNA fraction from 102 mCRPC patients receiving abiraterone or enzalutamide.

Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration-resistant cancer patients.

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC.

Melphalan as a Promising Treatment for BRCA-Related Ovarian Carcinoma.

Introduction: Melphalan, as a bifunctional alkylating agent has been shown to be selectively efficient in BRCA-deficient case reports of epithelial ovarian cancer (EOC). The clinical benefit of melphalan on unselected platinum-resistant EOC population and stratified by BRCA status has not been clearly elucidated. We aimed to determine the response to melphalan in patients with recurrent EOC after platinum-based therapy.

Docetaxel and prednisone with or without enzalutamide as first-line treatment in patients with metastatic castration-resistant prostate cancer: CHEIRON, a randomised phase II trial.

Background: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC).

Methods: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D).

Plasma androgen receptor and response to adapted and standard docetaxel regimen in castration-resistant prostate cancer: A multicenter biomarker study.

Background: Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown.

Patients And Methods: This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician.

Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review.

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic.

An update on our ability to monitor castration-resistant prostate cancer dynamics with cell-free DNA.

: Prostate cancer is one of the most frequent tumors worldwide. Due to the lack of reliable markers, patients are usually diagnosed at a late stage when it becomes castration-resistant prostate cancer (CRPC) with a worse outcome. Thus, it is essential to ameliorate the clinical management of these patients.