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Background: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear., Methods: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks., Results: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass., Conclusions: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT., (© 2024 American Cancer Society.)

Introduction: Lurbinectedin is FDA approved for treatment of metastatic small cell lung cancer (SCLC) following progression on or after platinum-based chemotherapy. Prostatic small cell or neuroendocrine carcinoma (SC/NEPC) behaves like SCLC; however, no safety or efficacy data for lurbinectedin in SC/NEPC exists., Patients and Methods: All SC/NEPC patients treated with lurbinectedin across 4 academic oncology centers were identified. Baseline patient data and lurbinectedin outcomes including radiographic responses (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]), progression free survival (PFS), overall survival (OS), and treatment-related adverse events (trAEs) were described. Clinical benefit rate (CBR) included CR, PR, or SD on imaging. Descriptive statistics were performed., Results: At first lurbinectedin dose, all 18 patients had metastatic disease. Median age was 63.5 (Range: 53-84), number of prior systemic therapies was 4 (Range: 2-7), and lurbinectedin cycles completed was 5 (Range: 1-10). ADT was administered during lurbinectedin treatment in 9/18 patients. CBR was 9/16 (56%). The most common trAEs were fatigue and anemia. Median OS and PFS were 6.01 (0.23-16.69) and 3.35 (0.16-7.79) months., Conclusions: Lurbinectedin showed modest but significant clinical benefit in some patients with SC/NEPC and demonstrated an acceptable toxicity profile with no hospitalizations from trAEs. SC/NEPC is an aggressive disease with a poor prognosis for which more treatment options are needed. Evidence for subsequent treatments after platinum-based chemotherapy is lacking. Lurbinectedin is an active treatment option for SC/NEPC; however, larger confirmatory studies are needed., Competing Interests: Disclosures Haley M Meyer. No Relationships to Disclose, Rajitha Sunkara, No Relationships to Disclose, Himisha Beltran, Consulting or Advisory Role - Amgen; AstraZeneca; Bayer; Blue Earth Diagnostics; Curie Therapeutics; Daicchi Sankyo; Foundation Medicine; Janssen Oncology; Loxo/Lilly; Merck; Novartis; Pfizer; Sanofi, Research Funding - Abbvie/Stemcentrx (Inst); Bristol Myers Squibb Foundation (Inst); Daiichi Sankyo (Inst); Janssen (Inst). Travel, Accommodations, Expenses - Janssen Oncology, Emily Rothmann, No Relationships to Disclose, Kevin Dale Courtney. Consulting or Advisory Role - Novartis, Research Funding - Amgen (Inst); Astellas Pharma (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Celgene/Bristol-Myers Squibb (Inst); Clovis Oncology (Inst); Exelixis (Inst); Harpoon therapeutics (Inst); Lilly (Inst); Myovant Sciences (Inst); Novartis (Inst); Pfizer (Inst); Stemline Therapeutics (Inst); Surface Oncology (Inst), Patents, Royalties, Other Intellectual Property - My spouse receives patent royalties from Athena Diagnostics, Inc. (I) Andrew J. Armstrong. Consulting or Advisory Role - Astellas Scientific and Medical Affairs Inc; AstraZeneca; Bayer; Bristol-Myers Squibb; Epic Sciences; Exelixis; GoodRx; Janssen; Merck; Myovant Sciences; Novartis; Pfizer; ZAlpha, Research Funding - Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bayer (Inst); BeiGene (Inst); Bristol-Myers Squibb (Inst); Bristol-Myers Squibb (Inst); Constellation Pharmaceuticals (Inst); FORMA Therapeutics (Inst); Gilead Sciences (Inst); Janssen Oncology (Inst); Merck (Inst); Novartis (Inst); Pfizer (Inst); Roche/Genentech (Inst), Patents, Royalties, Other Intellectual Property - Circulating tumor cell novel capture technology (Inst), Travel, Accommodations, Expenses - Astellas Scientific and Medical Affairs Inc, Alan Haruo Bryce, Honoraria - Advanced Accelerator Applications/Novartis; Astellas Pharma; Astellas Pharma; AstraZeneca; Bayer; Bayer; Bayer; Castle Biosciences; Horizon CME; Janssen; Janssen Oncology; Lilly; Myovant Sciences; Myovant Sciences; Novartis; Novartis; Pfizer; Pfizer; Pfizer; Research to Practice; Research to Practice; Verity Pharmaceuticals; Verity Pharmaceuticals, Consulting or Advisory Role - Astellas Pharma, Research Funding - Janssen Oncology (Inst). Travel, Accommodations, Expenses - Bayer; Clovis Oncology (Inst); Pfizer; Pfizer (Inst); Phosplatin Therapeutics (Inst), Andrea Lippucci, Andrea Lippucci is currently a Genitourinary Oncology medical science liaison for Johnson and Johnson. The content production and involvement with this research project and manuscript were completed prior to her employment with Johnson and Johnson. This publication in no way reflects the viewpoint of Johnson and Johnson nor is it an endorsement of a particular treatment approach. Melissa L. Stanton, Consulting or Advisory Role - PAREXEL, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Guidelines recommend somatic and germline testing for men with advanced prostate cancer (PCa). Barriers to widespread implementation result in underutilization of germline testing. Somatic testing alone risks missing pathogenic germline variants (PGVs). We sought to determine whether the addition of germline testing to tumor-only sequencing improves detection of PGVs in men with advanced PCa. Secondarily, we sought to define the added value of combining somatic and germline testing to optimize detection of clinically actionable alterations., Patients and Methods: We analyzed results of independent germline testing and tumor-only sequencing from 100 men with advanced PCa from a prospective clinical trial (ClinicalTrials.gov identifier: NCT03328091). The primary outcome was the proportion of PGVs not reported with tumor-only sequencing. The secondary outcome was the association of locus-specific loss of heterozygosity for PGVs in homologous recombination genes with clinical-genomic features., Results: In the 100 men who underwent germline testing and tumor-only sequencing, 24 PGVs were identified, 17 of which were clinically actionable, in 23 patients. Tumor-only sequencing failed to report four (17%) of the PGVs. One additional PGV (4.2%) had variant allele frequency on tumor-sequencing below the threshold for follow-up germline testing. When integrating tumor-only sequencing with germling testing results, 33% of patients harbored clinically actionable alterations. Rates of locus-specific loss of heterozygosity were higher for BRCA2 PGVs in castration-resistant PCa than PGVs in other homologous recombination genes in hormone-sensitive PCa ( P = .029)., Conclusion: Tumor-only sequencing failed to report more than 20% of PGVs in men with advanced PCa. These findings strongly support guideline recommendations for universal germline and somatic testing in this population. Combining tumor and germline sequencing doubled the chance of detecting a clinically actionable alteration.

A 24-year-old woman underwent video-assisted thoracoscopic thymectomy for Osserman IIB myasthenia gravis (MG). In preparation for thymectomy, high-dose intravenous immunoglobulin (IVIG) was administered 1 week before the surgical procedure. After uneventful thoracoscopic thymectomy, the postoperative hemoglobin value decreased from 12.1 mg/dL to 8.2 mg/dL. A diagnosis of IVIG-associated hemolytic anemia was made based on a peripheral smear with numerous spherocytes, a positive direct antiglobulin test result, and increased reticulocyte count. Hemoglobin levels after IVIG administration should be monitored closely before and after elective surgical procedures to identify severe anemia. Transfusion of type-matched blood should be avoided and risk factors understood., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report a case of 68 years old gentleman who developed a delayed local recurrence, 30 years following curative radiation treatment for muscle invasive bladder cancer. This case emphasizes the importance of lifelong post treatment surveillance for bladder cancer.