Circulating microRNA-155-3p levels predicts response to first line immunotherapy in patients with metastatic renal cell carcinoma.

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties.

DPYSL5 is highly expressed in treatment-induced neuroendocrine prostate cancer and promotes lineage plasticity via EZH2/PRC2.

Treatment-induced neuroendocrine prostate cancer (t-NEPC) is a lethal subtype of castration-resistant prostate cancer resistant to androgen receptor (AR) inhibitors. Our study unveils that AR suppresses the neuronal development protein dihydropyrimidinase-related protein 5 (DPYSL5), providing a mechanism for neuroendocrine transformation under androgen deprivation therapy. Our unique CRPC-NEPC cohort, comprising 135 patient tumor samples, including 55 t-NEPC patient samples, exhibits a high expression of DPYSL5 in t-NEPC patient tumors.

The Use of Salvage Chemotherapy for Patients with Relapsed Testicular Germ Cell Tumor (GCT) in Canada: A National Survey.

Background: Although metastatic germ cell tumor (GCT) is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remain lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada.

Surgery in Early Metastatic Seminoma: A Phase II Trial of Retroperitoneal Lymph Node Dissection for Testicular Seminoma With Limited Retroperitoneal Lymphadenopathy.

Purpose: The long-term toxicities of chemotherapy and radiotherapy can represent a significant burden to testicular cancer survivors. Retroperitoneal lymph node dissection (RPLND) is an established treatment for testicular germ cell tumors with minimal late morbidity although little data exist on its efficacy in early metastatic seminoma. Surgery in early metastatic seminoma is a prospective phase II single-arm, multi-institutional trial of RPLND as first-line treatment for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy.

Primary Mediastinal Germ Cell Tumors: A Thorough Literature Review.

Primary mediastinal germ cell tumors (PMGCTs) are a rare type of cancer affecting young adults. They have different molecular and clinical features compared to testicular germ cell tumors. Non-seminoma PMGCTs have the shortest 5-year overall survival and the poorest prognosis among all of the germ cell tumor presentations, while seminomas share the same survival and prognosis as their testicular counterparts.

Genomic features of mediastinal germ cell tumors: a narrative review.

Background And Objective: Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80% develop from the mediastinum. While the prognosis of seminomas is not affected by the gonadal or extragonadal primary location, the prognosis of nonseminoma primary mediastinal GCTs (NS-PMGCTs) is poor, compared to its gonadal counterpart with an estimated 5-year overall survival of about 50%.

Exploring new frontiers in prostate cancer research: Report from the 2022 Coffey-Holden prostate cancer academy meeting.

Introduction: The 2022 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Exploring New Frontiers in Prostate Cancer Research," was held from June 23 to 26, 2022, at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.

Methods: The CHPCA Meeting is an annual discussion-oriented scientific conference organized by the Prostate Cancer Foundation, that focuses on emerging and next-step topics deemed critical for making the next major advances in prostate cancer research and clinical care. The 2022 CHPCA Meeting included 35 talks over 10 sessions and was attended by 73 academic investigators.

Comprehensive immune profiling of patients with advanced urothelial or renal cell carcinoma receiving immune checkpoint blockade.

Immune checkpoint inhibitors (ICI) are used in the treatment of urothelial and renal cell cancers. While some patients may have exceptional responses, better predictive biomarkers are needed. We profiled the circulating immune compartment of patients receiving ICI to identify possible immune markers associated with immunotherapy response or resistance.

TP53 Alterations Are Associated With Poor Survival in Patients With Primary Mediastinal Nonseminoma Germ Cell Tumors.

Background: Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes.

Methods: DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma).

Emerging Role of Biomarkers in Testicular Germ Cell Tumors.

Purpose Of Review: This review will focus on biomarkers in testicular germ cell tumors (TGCT), focusing on microRNAs with high potential clinical application to drive management of TGCT. We explore the mechanism of action of microRNAs, literature to date, and how microRNAs may be incorporated into clinical practice in the near future.

Recent Findings: MicroRNAs are small non-coding RNAs found in blood which play an important role in post-transcriptional gene regulation and have been explored in TGCT for the past 15 years.

Narrative review of developing new biomarkers for decision making in advanced testis cancer.

Management of testicular germ cell tumor (GCT) patients is based on clinical determinants, mainly CT scan and serum tumor markers (alpha-fetoprotein, beta subunit of HCG and LDH). Treatment decisions are usually straightforward for patients with clear evidence of metastatic disease, confirmed either by imaging tests or by unequivocal elevated tumor markers. However, there are several clinical scenarios where the assessment of metastatic disease is complicated by the limited specificity of the current imaging tests and serum tumor markers.

Primary pure carcinoid tumor of the testis: Radiology, pathology and molecular correlation.

We describe a case of a primary carcinoid tumor of the testis in a 35-year-old man as an incidental finding. Testicular ultrasound showed a 1.1 cm hypoechoic/isoechoic mass with some calcification in the left testicle.

Effectiveness of first-line abiraterone versus enzalutamide among patients ≥80 years of age with metastatic castration-resistant prostate cancer: A retrospective propensity score-weighted comparative cohort study.

Background: Metastatic castration-resistant prostate cancer (mCRPC) disproportionately affects the elderly. There is limited data assessing the efficacy and tolerability of abiraterone acetate (AA) versus enzalutamide in this population.

Objective: To compare the clinical efficacy and tolerability of AA versus enzalutamide in patients ≥ 80 years with mCRPC.

Androgen receptor (AR) antagonism triggers acute succinate-mediated adaptive responses to reactivate AR signaling.

Treatment-induced adaptive pathways converge to support androgen receptor (AR) reactivation and emergence of castration-resistant prostate cancer (PCa) after AR pathway inhibition (ARPI). We set out to explore poorly defined acute adaptive responses that orchestrate shifts in energy metabolism after ARPI and identified rapid changes in succinate dehydrogenase (SDH), a TCA cycle enzyme with well-known tumor suppressor activity. We show that AR directly regulates transcription of its catalytic subunits (SDHA, SDHB) via androgen response elements (AREs).

In Reply.

This letter to the editor responds to the question of whether delayed administration of chemotherapy in patients diagnosed with COVID‐19 is necessary and suggests the importance of evaluating each case carefully before the decision is made.

Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors.

Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumor patients, divided into two cohorts, were enrolled in a prospective multi-institutional study.

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.

Avelumab and axitinib combination therapy for the treatment of advanced renal cell carcinoma.

Owing to an improved understanding of the immunobiological profile of renal cell carcinoma (RCC), the past few years have ushered in significant changes in systemic therapies for advanced stage RCC. First-line treatment with single-agent tyrosine kinase inhibitors (TKI) has been virtually replaced for most patients by immunotherapy combinations. The first of such treatments was the dual immune checkpoint inhibitor combination of ipilimumab and nivolumab.

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

Background: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs).

Materials And Methods: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada.