BACKGROUND/AIM:Prostate cancer is one of the most common malignancies in men. Although androgen deprivation therapy (ADT) offers substantial benefit, resistance to androgen signaling ultimately develops, leading to castration-resistant prostate cancer (CRPC). Approximately 10-17% of CRPC cases evolve into treatment-induced neuroendocrine prostate cancer (t-NEPC), an aggressive, androgen receptor (AR)-independent subtype. The TMPRSS2-ERG fusion gene is among the most frequent genomic alterations in prostate cancer; however, its involvement in t-NEPC development remains unclear. PATIENTS AND METHODS:We retrospectively analyzed nine Japanese cases of t-NEPC diagnosed across multiple institutions. Immunohistochemical staining for AR and ERG and RT-PCR for TMPRSS2-ERG fusion gene expression were performed on paired adenocarcinoma and t-NEPC samples. Clinical data - including prostate specific antigen levels, Gleason scores, metastatic patterns, and outcomes - were compared between ERG-positive and ERG-negative groups. RESULTS:ERG-positive prostate cancer was found in three of nine cases (33.3%), all of which were AR-positive, indicating that active AR signaling is required for TMPRSS2-ERG expression. ERG positivity was not clearly associated with prognosis or drug sensitivity, but time to NEPC differentiation tended to be shorter in ERG-positive cases. Only the e1e4 isoform of TMPRSS2-ERG was detected, while e2e4 was absent. CONCLUSION:This study highlights heterogeneity in TMPRSS2-ERG fusion dynamics during t-NEPC evolution and suggests a potential association between ERG expression and earlier NE differentiation. This study provides a rare opportunity to analyze paired pre- and post-NEPC tissues, offering valuable insight into the relationship between ERG and TMPRSS2-ERG fusion gene expression and clinical parameters.
BACKGROUND:Sarcopenia is increasingly recognized as a prognostic factor in oncology; however, most studies have focused on static baseline muscle mass in heterogeneous populations. Whether dynamic skeletal muscle loss during systemic therapy carries independent prognostic value, particularly in clinically stable patients with controlled disease, remains unclear. We investigated the prognostic relevance of three-dimensional volumetric muscle assessment in advanced urothelial carcinoma (UC) patients who achieved disease control with first-line platinum-based chemotherapy and subsequently received maintenance therapy. METHODS:This multicenter retrospective study included 82 patients with unresectable or metastatic UC across 10 institutions. Psoas muscle volume (PMV) was quantified using three-dimensional computed tomography (CT) reconstruction. The relative percentage change in PMV during induction chemotherapy (ΔPMV) was calculated as: (PMV at pre-maintenance - PMV at baseline)/PMV at baseline × 100. A predefined PMV loss ≥ 5% (defined as ΔPMV ≤ -5%) was considered clinically significant. Baseline cross-sectional muscle indices, including skeletal muscle index (SMI), total psoas index (TPI), and paraspinal muscle index (PMI), as well as inflammatory and nutritional markers, were evaluated. Overall survival (OS) was analyzed using multivariable Cox regression. RESULTS:During a median follow-up of 19 months, 35 deaths occurred. Baseline cross-sectional muscle indices (SMI, TPI, and PMI) were not associated with OS. In contrast, patients with PMV loss ≥ 5% (ΔPMV ≤ -5%) had significantly shorter OS. In multivariable analysis adjusting for clinical, inflammatory, and nutritional factors, PMV loss ≥ 5% remained independently associated with worse OS (HR 2.14, 95% CI 1.02-4.50, p = 0.044). Dynamic volumetric muscle decline may reflect clinically meaningful physiologic vulnerability despite tumor control. CONCLUSIONS:Dynamic loss of PMV during systemic therapy is a strong independent prognostic marker in advanced UC patients with controlled disease, whereas static baseline muscle indices lack prognostic significance. These findings highlight the clinical importance of preserving skeletal muscle mass during systemic therapy and support further investigation of targeted nutritional or supportive interventions.
Background:The Institut Mutualiste Montsouris (IMM) 3-level complexity classification has been validated for laparoscopic liver resection (LLR) in several studies with small sample size. However, it has not been well-validated in large studies down to the individual procedure type. Hence, in order to address current limitations in the studies validating the IMM complexity classification, we performed an international multicenter study to validate the IMM complexity classification across its three complexity levels and the categorization of the 11 distinct procedure types. Methods:A retrospective cohort study of 22,252 patients undergoing LLR across 64 centers worldwide between 2005 and 2021 was performed. Baseline characteristics and perioperative outcomes were analyzed across the three difficulty levels and 11 procedure types of the IMM complexity classification. Results:A total of 14,765 patients were included in our final analysis. The main indications for LLR in our study was hepatocellular carcinoma or intrahepatic cholangiocarcinoma (n=7,781, 52.7%) followed by liver metastasectomy (n=3,911, 26.5%). In terms of underlying liver pathology, 5,127 (34.7%) cases had cirrhosis, and 1,214 (8.3%) had portal hypertension. Perioperative outcomes including operative time, open conversion rate, intraoperative blood loss, need for intraoperative blood transfusion, need for Pringle's application, length of stay, postoperative morbidity, major postoperative morbidity and 90-day mortality all demonstrated a significant increasing trend with increasing IMM complexity grades (P<0.001). These trends remained significant following adjustment for baseline characteristics (P<0.001). Notably, when examining the 11 LLR procedure types, all procedures within each IMM complexity grade were individually higher than all procedures in the preceding complexity grade for operative time, blood loss, length of stay, postoperative morbidity and major postoperative morbidity. Conclusions:The three IMM complexity grades were well associated with LLR complexity as determined by key surrogate perioperative measures. Our findings also supported the categorization of the 11 distinct LLR procedures into the three complexity levels.
Background The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. Patients and methods Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). Results Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. Conclusion Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.
