Genitourinary syndrome of menopause is a chronic and high prevalent condition with a substantial negative impact in women's quality of life and vaginal health. The prevalence of GSMis even higher among breast cancer survivors receiving endocrine adjuvant therapy. This study aimed to evaluate the efficacy and safety of CO2 laser (CO2L), radiofrequency (RF), and promestriene in treating genitourinary syndrome of menopause (GSM) in this population. A multi-arm randomized clinical trial enrolled postmenopausal women with breast cancer undergoing endocrine adjuvant therapy. Participants were randomized to receive CO2L, RF, or promestriene treatment. The study assessed before, 4, and 10 months after treatment GSM symptoms, Vaginal Health Index (VHI), sexual function, and urinary symptoms using validated tools. Statistical analysis was performed to compare treatment outcomes and adverse events. The intensity and frequency of GSM signs and symptoms before and after the proposed therapies were evaluated, along with their impact on health-related quality of life, patient satisfaction, and the presence of adverse events related to the treatments, during the 10 months follow-up. Fifty-eight women completed the treatment and the 10-month follow-up (21 CO2L, 19 RF, 18 promestriene). The groups were similar regarding the intensity of vaginal health symptoms and demographic parameters. All treatment groups showed significant improvement in GSM symptoms, VHI, and sexual function. Urinary symptoms were reduced in the CO2L and RF groups, with sustained improvement at the 10-month follow-up. Adverse events were mild and well tolerated, with no serious complications reported. CO2L, RF, and promestriene demonstrated efficacy in improving GSM symptoms, VHI, and sexual function in breast cancer survivors receiving adjuvant endocrine therapy. These treatments offer safe and effective alternatives for managing GSM in this population, with potential benefits for health-related quality of life and treatment adherence.
Statins and ezetimibe are widely used and safe lipid-lowering therapies for the prevention of atherosclerotic cardiovascular disease. However, concerns persist, especially among the lay public, about the possibility of a long-term association with cancer incidence and cancer-related mortality. To evaluate the association between statin therapy, statin intensity, ezetimibe, and statin-ezetimibe combination therapy with cancer incidence and cancer-related mortality using a network meta-analysis of randomized controlled trials. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials comparing statin monotherapy, statin-ezetimibe combination, or ezetimibe monotherapy with no lipid-lowering therapy (no-LLT), including head-to-head comparisons of statin intensities. PubMed/MEDLINE, Embase, and Cochrane were searched through February 2026. Treatment effects were estimated using random-effects Bayesian models and expressed as risk ratios (RRs) with 95% credible intervals (CrIs). A total of 69 randomized controlled trials, including 238,533 participants, were analyzed, of whom 199,286 received statins, 35,836 received statins plus ezetimibe, and 3,411 received ezetimibe alone. For cancer incidence, high-intensity statins (RR 0.95, 95% CrI 0.87-1.03), moderate-intensity statins (RR 1.01, 95% CrI 0.96-1.05), low-intensity statins (RR 1.06, 95% CrI 0.72-1.61), and moderate-intensity statin plus ezetimibe (RR 1.04, 95% CrI 0.96-1.14) were not associated with a reduction compared with no-LLT. For cancer mortality, no significant differences were observed with high-intensity statins (RR 0.94, 95% CrI 0.79-1.09), moderate-intensity statins (RR 1.00, 95% CrI 0.92-1.08), low-intensity statins (RR 1.70, 95% CrI 0.50-6.06), moderate-intensity statin plus ezetimibe (RR 1.12, 95% CrI 0.97-1.32), or ezetimibe alone (RR 1.32, 95% CrI 0.82-2.15), all compared with no-LLT. All head-to-head comparisons among active treatment nodes (statin intensities, statin-ezetimibe combination, and ezetimibe monotherapy) were similarly null, with point estimates close to unity and 95% CrIs crossing 1.0 for all comparisons. Node-splitting revealed no significant inconsistency between direct and indirect evidence for any evaluable comparison. Subtype analyses for lung, breast, gastrointestinal, genitourinary, hematological, skin, and central nervous system cancers showed no significant differences across treatment strategies. In this network meta-analysis of randomized trials, statin therapy across all intensities and ezetimibe, alone or in combination, were not associated with an increased risk of cancer incidence or cancer-related mortality, supporting their oncologic safety within the duration of follow-up available in randomized clinical trials. This study found no evidence that statins, ezetimibe, or their combination increase the risk of developing or dying from cancer during the follow-up evaluated in randomized clinical trials.We analyzed data from 69 randomized clinical trials involving more than 238,000 participants and found no increased risk of overall cancer, cancer-related death, or any major cancer subtype with statins, ezetimibe, or statin-ezetimibe combination therapy.These findings provide reassurance regarding the cancer safety of guideline-recommended lipid-lowering therapies while emphasizing that longer-term studies remain important to evaluate potential very late cancer outcomes.
Inhibition of androgen receptor (AR) signaling remains the cornerstone of systemic therapy for advanced prostate cancer (PC). However, a subset of aggressive tumors either arises de novo with neuroendocrine features or emerges under treatment pressure through lineage plasticity and AR independence. These lethal states are encompassed within the spectrum of aggressive-variant prostate cancer (AVPC), an umbrella term that includes both histologically confirmed neuroendocrine prostate cancer (NEPC)-comprising de novo NEPC and treatment-emergent NEPC (t-NEPC)-and clinically or molecularly defined AVPC lacking histologic confirmation but sharing neuroendocrine-like, AR-indifferent, or small-cell features. These phenotypes are characterized by rapid progression, visceral dissemination, low or discordant prostate-specific antigen (PSA) levels relative to tumor burden, and poor prognosis. Treatment options for NEPC/AVPC remain limited and largely rely on platinum-based chemotherapy, which usually provides only modest and transient benefit. This unmet need has intensified interest in lineage-associated vulnerabilities. Delta-like ligand 3 (DLL3), an inhibitory Notch ligand with restricted expression in normal adult tissues, is aberrantly upregulated in several neuroendocrine malignancies and has emerged as a clinically actionable target. In prostate cancer, DLL3 expression is enriched in neuroendocrine tumor cells, being detected in approximately 76.6% of castration-resistant NEPC compared with only 12.5% of castration-resistant adenocarcinoma, supporting its development as both a biomarker and therapeutic vulnerability. Clinical success of DLL3-targeted therapies in small-cell lung cancer further supports evaluation of DLL3-directed strategies in NEPC and related AVPC states. This review summarizes the biological rationale, translational evidence, and emerging clinical data supporting DLL3-targeted therapies in prostate cancer. Investigational platforms include antibody-drug conjugates, bispecific and trispecific T-cell engagers, and DLL3-directed radiopharmaceuticals. Early clinical studies suggest that activity is largely confined to DLL3-expressing neuroendocrine tumors, highlighting the importance of biomarker-guided patient selection. Delta-like ligand 3-directed therapies may reshape the management of DLL3-expressing prostate cancer if ongoing efforts to refine biomarkers improve patient enrichment and optimize trial design are successfully translated into clinical practice.
Histological subtypes of bladder cancer are generally associated with more aggressive disease, higher stage at presentation, and worse prognosis compared to conventional urothelial carcinoma. Recent updates in classification systems have further refined the distinction between true histologic subtypes and divergent differentiation, underscoring the complexity of these tumors. Emerging molecular profiling studies have identified subtype-specific genomic alterations, including ERBB2 amplification in micropapillary subtype carcinoma, CDH1 loss in plasmacytoid subtype carcinoma, and TP53 and RB1 co-alterations in neuroendocrine bladder cancer, which may contribute to differences in tumor biology and therapeutic response. Despite these advances, the histological subtypes of bladder cancer remain underrepresented in prospective clinical trials, leading to significant gaps in evidence-based management. Treatment responses vary widely across subtypes, with some demonstrating sensitivity to platinum-based chemotherapy or immunotherapy, while others appear less responsive to conventional approaches. This review summarizes the current understanding of the epidemiology, molecular landscape, and clinical behavior of major bladder cancer subtypes and highlights emerging opportunities for personalized treatment strategies, biomarker-driven therapies, and more inclusive clinical trial design to improve outcomes in this high-risk population.
Urothelial cancer typically affects older adults, yet early-onset urothelial cancer (EO-UC, age ≤ 45 years) cases are rising and remain poorly characterized. We hypothesized that EO-UC exhibits distinct clinical and genomic features that reflect a different biological etiology from standard-onset UC (SO-UC). We compared clinical, pathologic, and genomic characteristics of patients with EO-UC versus SO-UC evaluated at Memorial Sloan Kettering Cancer Center from 2000 through 2024. Clinical data included 9,221 patients, with tumor and germline genomic profiling by MSK-IMPACT in 2,753 patients. EO-UC accounted for 335/9,221 (3.6%) cases. EO-UC patients were more likely never-smokers (43% vs 26%, p < 0.001), female (30% vs 25%, p = 0.034), and of Asian race (7.4% vs 3.1%, p < 0.001). EO-UC tumors were more often low-grade (41% vs 23%, p < 0.001) and of pure non-urothelial histology (4.0% vs 1.7%, p = 0.003). EO-UC showed marked enrichment for HRAS mutations, independent of histologic subtype, and HRAS-mutated tumors had reduced APOBEC-associated mutation signatures. Germline pathogenic variants were detected in 21.0% of EO-UC vs 17.2% of SO-UC patients (p = 0.43), driven mostly by mismatch repair and MUTYH gene alterations. Rare cases of somatic mosaicism in HRAS and ERCC2 were observed in patients with very early-onset disease. EO-UC represents a biologically distinct subset characterized by HRAS-driven oncogenesis, reduced APOBEC mutagenesis, frequent germline variants, and, rarely, somatic mosaicism. These findings suggest developmental or genetic mechanisms underlying EO-UC, and supporting age- and biology-informed approaches to risk assessment, genetic counseling, and targeted therapy development.
Atrial fibrillation (AF) and cancer frequently coexist, particularly in elderly patients, creating a complex clinical scenario with both increased thromboembolic and hemorrhagic risk. In these patients, in addition to established risk factors, cancer-related factors, such as thrombocytopenia, organ dysfunction, and drug-drug interactions, should be considered when managing anticoagulant treatment. Despite the growing prevalence of this clinical overlap, cancer patients have been under-represented in randomized controlled trials of direct oral anticoagulants for AF. Consequently, evidence guiding anticoagulation decisions in this population derives largely from post-hoc analyses and observational studies. The CHA₂DS₂-VA(Sc) and HAS-BLED scores, widely used for thromboembolic and bleeding risk stratification in the general AF population, have demonstrated suboptimal predictive performance in cancer patients, underscoring the need for a risk factor based approach specific for cancer patients. Emerging data consistently suggest that direct oral anticoagulants (DOACs) are at least as effective and safe as vitamin K antagonists (VKAs) in cancer patients with AF, with potential advantages in reducing stroke, major and intracranial bleeding, and mortality. However, DOACs use is still debated in some settings such as gastrointestinal and genitourinary cancer, brain metastasis and in case of strong drug-drug interactions. This review summarizes current evidence on ischemic and bleeding risk assessment in cancer patients with AF, evaluates the performance of existing risk stratification tools, identifies cancer-specific bleeding risk factors, and proposes a practical management algorithm for anticoagulation in this challenging population.
Recent advances in cancer screening, diagnosis, and treatment have greatly improved survival rates among women with gynecologic cancers. More survivors now live long enough to experience treatment-related menopause. Vasomotor symptoms, genitourinary syndrome of menopause, sexual dysfunction, sleep issues, and long-term risks from estrogen deficiency can seriously impact quality of life. Despite increased survival, managing menopausal symptoms remains difficult, as concerns about cancer recurrence and hormone therapy safety often result in inconsistent or insufficient treatment. This article explores clinical considerations for menopausal hormone therapy (MHT) in women with a history of gynecologic cancer. It reviews evidence on the safety of MHT after vulvar, vaginal, cervical, uterine, and ovarian cancers, providing an overview of tumor histology, stage, and hormonal sensitivity. It also synthesizes observational studies, systematic reviews, and international guidelines to help clinicians deliver menopausal care to cancer survivors. Current evidence suggests that systemic MHT may be suitable for carefully chosen survivors of non-hormone-dependent gynecologic cancers, including most vulvar, vaginal, cervical, and epithelial ovarian cancers. Patients with hormonally sensitive tumors should generally avoid systemic MHT, while local vaginal hormonal administration and non-hormonal options remain important in these cases. Given the disproportionate burden of gynecologic cancers in low- and middle-income countries, where younger women face increased risks of treatment-induced menopause and limited survivorship resources, this paper emphasizes context-specific, resource-aware strategies to promote equitable care. By enhancing personalized and evidence-based decision-making, we aim to improve quality of life for women during menopause after cancer treatment, while ensuring safe, fair, and widely applicable survivorship approaches.
Clinical research has evolved into a multidisciplinary field integrating Medical Devices (MD), In Vitro Diagnostics (IVD), and Artificial Intelligence (AI), governed by a modernized European regulatory framework including the Clinical Trial Regulation (CTR), the Medical Device Regulation (MDR), and the In Vitro Diagnostics Regulation (IVDR). In 2021, the Istituto Oncologico Veneto (IOV) IRCCS established the Clinical Trial Quality Team (CTQT) to provide support for non-profit trials and ensure high-quality standards. A descriptive analysis of trials managed between 2021 and 2025 was conducted using the REDCap platform. A team of 15 professionals assessed performance via Key Performance Indicators (KPIs) categorized into: ethical-regulatory compliance, operational efficiency and data quality. The CTQT manages 18 studies (83% interventional, 50% multicentre), primarily focused on brain (17%) and genitourinary (23%) tumours. The mean time from internal feasibility to Ethics Committee discussion is 13 days. Total approval time (ethical and administrative) is 107 days. Operational metrics are strong, with Site Initiation Time averaging 27 days and First Patient In (FPI) at 41 days. A centralized, multidisciplinary structure effectively supports non-profit research in a complex regulatory environment. While operational speed is high, challenges such as staff turnover and query management variability remain. Future efforts will focus on standardizing post-approval administrative phases and optimizing data management to further improve trial efficiency and integrity.
Speaker roles at major international oncology meetings mark academic visibility and leadership, yet representation of Latin America and Caribbean (LAC)-affiliated investigators remains poorly characterized. We evaluated LAC-affiliated faculty appearances at the ASCO Genitourinary Cancers Symposium (ASCO GU) from 2021 to 2025. We systematically reviewed ASCO GU programs (2021-2025). Eligible sessions included General Session, Oral Abstract Session, and Rapid Oral Abstract Session. Affiliation was determined by institutional listing. We recorded total faculty appearances and stratified faculty appearances into invited educational, abstract-linked, and leadership roles. We additionally examined discussant and moderator appearances separately and identified the assigned speaker for each Oral or Rapid Oral presentation with at least one LAC-affiliated author. Among 84 eligible sessions comprising 540 faculty speakers, only six LAC-affiliated faculty appearances were identified, representing only 1% of the total faculty. No LAC-affiliated faculty appeared in 2021 or 2022, with minimal representation in subsequent years (2023: n = 1; 2024: n = 2; 2025: n = 3). By contrast, LAC-affiliated investigators were identified in 53 appearances as authors or coauthors in Oral or Rapid Oral sessions, predominantly affiliated with institutions in Brazil, Argentina, Chile, Mexico, and Colombia. Three of six LAC-affiliated faculty were linked to specific clinical trial presentations rather than independent educational lectures. LAC-affiliated investigators remain markedly under-represented among ASCO GU faculty despite robust scientific contributions, highlighting potential structural inequities and the need for deliberate initiatives to support equitable participation in international scientific discourse.
We report a rare case of adenocarcinoma with endometrioid features in an 80-year-old male with a history of long-term hormonal therapy for prostate cancer. Over a 13-year course of estrogen therapy, multiple lesions developed sequentially, beginning approximately three years after treatment initiation. These lesions involved the left vas deferens, prostatic urethra, and left pelvic-to-inguinal region. Histologically, the prostatic lesion showed adenocarcinoma with endometrioid features, whereas the other lesions demonstrated features reminiscent of atypical endometrial hyperplasia or an ovarian-type endometrioid borderline tumor. Notably, all specimens showed a consistent immunoprofile characterized by positivity for PAX8, ER, PgR, and negativity for NKX3.1, supporting a Müllerian origin. Although previous reports have suggested an association between endometrioid tumors and estrogen therapy for prostate cancer, this case is distinctive in that sustained tumor regression and long-term survival were achieved solely through discontinuation of estrogen therapy. The clinical course and anatomical distribution of the lesions suggest a possibility of multicentric development from Müllerian remnants under prolonged hormonal stimulation.
The purpose of the present study is to confirm the efficacy and feasibility of moderately hypofractionated proton beam therapy (PBT) at a total dose of 63 Gy relative biological effectiveness (RBE) in 21 fractions for prostate cancer. This phase II clinical trial (PPS-002: UMIN 000017679) enrolled 125 men with histologically confirmed prostate cancer (cT1c-3aN0M0). The primary endpoint was grade ≥2 late gastrointestinal (GI) toxicities. Secondary endpoints included biochemical recurrence rates, clinical recurrence rates, overall survival (OS) and acute toxicities and late genitourinary (GU) toxicities. With a median follow-up period of 71.0 months (IQR: 60-84), the 5-year cumulative incidences of late grade 2 or higher GI and GU adverse events (AEs) were 3.3% and 8.1%, respectively. Biochemical recurrences were observed in three patients; no clinical recurrences occurred. The 5-year biochemical recurrence-free, clinical recurrence-free and OS rates were 97.6% (95% CI: 94.9-100.0), 100% and 97.5% (95% CI: 94.8-100.0), respectively. The long-term follow-up results of moderately hypofractionated PBT of 63 Gy (RBE) in 21 fractions confirmed low incidences of late AEs, successfully meeting the primary endpoint. Furthermore, the low incidence of tumor recurrence supports the overall safety and feasibility of this fractionation schedule.
There are few bladder-sparing treatment options for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer that are effective and have a manageable adverse event profile. Cretostimogene grenadenorepvec (hereafter, cretostimogene) is an oncolytic immunotherapy with dual mechanisms of action-it replicates in and lyses cancer cells with retinoblastoma-E2F pathway alterations and amplifies the immune response. We evaluated the response and safety/tolerability of cretostimogene in patients with high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer. BOND-003 Cohort C is a single-arm, international, phase 3 study done in 41 centres (community practices and academic centres) located in North America, Asia, and Australia. Sites were selected through a study team-led qualification process that evaluated feasibility, protocol alignment, operational capabilities, and regulatory readiness, as applicable. We enrolled patients aged at least 18 years with Eastern Cooperative Oncology Group performance status of 0-2 and pathologically confirmed, high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ, with or without resected high-grade Ta or T1 disease. Patients received intravesical cretostimogene (1 × 1012 viral particles per 0·8 mL per week) as 6-week induction followed by maintenance; re-induction was permitted for persistent disease at 3 months. The primary endpoint was centrally confirmed complete response at any time in patients who received at least one dose of cretostimogene and completed the 3-month assessment; safety was assessed in those who received at least one dose of cretostimogene. This trial is registered with ClinicalTrials.gov (NCT04452591) and is ongoing. Between Oct 9, 2020, and Aug 3, 2023, 165 patients were assessed for eligibility; 115 patients were enrolled in the study and 112 received cretostimogene. 83 (74%) were male and 29 (26%) were female; median age was 74·0 years (IQR 68·5-79·5). As of June 23, 2025, after a median follow-up of 25·8 months (IQR 22·1-33·1), complete response at any time was observed in 83 (75% [95% CI 66·3-83·2]) of 110 patients. 71 (63%) of 112 patients had at least one treatment-related adverse event, the most common being bladder spasm in 28 (25%) patients, pollakiuria in 25 (22%) patients, and micturition urgency in 23 (21%) patients; there were no grade 3 or 4 treatment-related adverse events and no treatment-related discontinuations or deaths. Two (2%) patients had serious treatment-related adverse events (one non-infective cystitis and one urinary bladder haemorrhage, both grade 2). Cretostimogene showed clinically meaningful anti-tumour response, with an adverse event profile characterised predominantly by low-grade, transient events. Cretostimogene shows promise as an innovative bladder-sparing treatment for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ. CG Oncology.
Acquired resistance to the CYP17 inhibitor abiraterone is a critical challenge in the clinical treatment of metastatic prostate cancer; however, the mechanisms driving this resistance remain elusive. This study suggests that aberrant RON expression plays an important role in the development of acquired abiraterone resistance in prostate cancer cells. Increased RON expression was observed in most clinical tumor samples with an abiraterone-insensitive phenotype. In established prostate cancer cell lines, aberrant RON expression is associated with increased abiraterone resistance and enhanced migratory activity. These effects are mediated through dual regulatory functions of DNA methyltransferase 1(DNMT1): RON-mediated regulation of the canonical methyltransferase activity of DNMT1, which inhibits receptor-interacting protein kinase 3(RIPK3) expression, leading to increased cellular survival with impaired RIPK3/MLKL-involved cell death signaling. Concurrently, RON-driven non-methyltransferase activity of DNMT1 is associated with altered mitochondrial functions, thereby potentially enhancing cellular migration. The multi-kinase inhibitor BMS-777607, which has activity against RON, in combination with abiraterone suppressed both proliferation and metastasis in abiraterone-resistant xenograft tumors. The discovery of the RON-DNMT1-RIPK3 functional axis and the association between RON-DNMT1 and mitochondrial bioenergetic activity in this work strongly suggest RON as a critical driver of abiraterone resistance and a potential therapeutic target in prostate cancer.
The onset of the COVID-19 pandemic in March of 2020 led to the delay of routine prostate cancer screening. While screening rates recovered after the first wave of the COVID-19 pandemic, the degree to which this recovery occurred in different populations remains unknown. We sought to determine the association of the COVID-19 pandemic with prostate cancer screening, particularly for traditionally underserved patients. We performed a retrospective cohort study using electronic health records (EHR) data from the Optum de-identified Electronic Health Record dataset for all male patients between the ages of 55 to 69 eligible for prostate cancer screening from quarter 1 (Q1) of 2016 through Q2 of 2021. We studied trends in prostate cancer screening over time using adjusted generalized estimating equation (GEE) logit models to account for clustering of data within patients. A total of 7,361,765 patients were included. After adjusting for all selected patient demographics, the percentage of eligible patients with prostate cancer screening per quarter decreased from 2.2% in Q4 of 2019 to 1.3% in Q2 of 2020. There was a rebound in screening to 2.3% in Q3 of 2020 and a subsequent decline to 1.6% in Q2 of 2021. This trend was seen even after stratifying based on age, race, ethnicity, Census division of residence, and insurance status. Prostate cancer screening rates declined during the first and second waves of the COVID -19 pandemic across all demographic groups. This trend was unaffected by patient characteristics, such as age, race, insurance status, or Census division of residence.
Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited therapeutic options in advanced and recurrent diseases. Advanced PSCC is typically managed with multimodal therapy, including neoadjuvant chemotherapy or chemoradiation followed by surgery; however, durable responses remain uncommon, and outcomes after recurrence are poor. Cancer vaccines represent a promising immunotherapeutic strategy, as these treatments induce tumor-specific immunity and heightened immune surveillance against penile cancer cells. While therapeutic cancer vaccines have not yet demonstrated consistent clinical efficacy as monotherapy in PSCC, their integration with complementary immune-modulating approaches, particularly immune checkpoint blockade, represents a rational strategy to enhance antitumor immunity. This review summarizes the rationale for vaccine development in PSCC, with emphasis on HPV-derived antigens, neoantigens, and emerging tumor-associated targets. We examine major vaccine platforms, including viral-vector, peptide-based, nucleic acid, and dendritic cell-based approaches. We also discuss how spatial transcriptomics, single-cell RNA sequencing, artificial intelligence-assisted antigen prediction, and nanotechnology-enhanced delivery systems may support future personalized vaccine development. Overall, therapeutic vaccines remain investigational in PSCC but may become relevant within biomarker-driven, combination-based immunotherapy strategies.
Prostate cancer is a leading cause of cancer-related morbidity and mortality in men, with a subset of patients developing aggressive, castrate-resistant disease. We describe an underrecognized pattern of thoracic metastasis - peribronchial cuffing - in patients with advanced prostate cancer, with the aim to elucidate clinical, radiographic, and pathologic features and thus facilitate early recognition and management. This was a retrospective case series conducted at a quaternary cancer center between February 2020 and June 2025. Patients with prostate cancer and radiographic evidence of peribronchial cuffing were identified through a multidisciplinary service review. Clinical data were abstracted, radiographic cross-sectional imaging findings were independently confirmed, pathologic specimens were revisited for histochemical staining with H-scoring, and next-generation sequencing results were analyzed. A total of nine patients demonstrated lower lobe-predominant peribronchial thickening, with 78% exhibiting right-sided involvement. All lesions were FDG- and/or PSMA-avid on positron emission tomography studies. Mediastinal lymphadenopathy and parenchymal lung metastases were concomitantly present in 66 and 22% of patients, respectively. The median time from PSA rise from baseline to cross-sectional imaging was 12.9 months, and from imaging to biopsy was 3.8 months. Tumor TP53 gene alterations were found in 66% of cases. In 33% of patients, the diagnosis of peribranchial metastases resulted in cancer upstaging. On follow-up, 55% of patients died within a median of 5.3 months from radiographic detection. Peribronchial metastasis represents a rare and underrecognized pattern of advanced prostate cancer spread. Its subtle presentation may result in delays in diagnosis and treatment. Recognition of this pattern in patients with rising PSA can be facilitated by new-generation molecular PET imaging studies to guide earlier biopsy and treatment initiation. Future studies are needed to characterize the pathobiologic mechanisms underlying this form of prostate cancer metastasis.
Background/Objectives: Metastatic prostate cancer is increasing in the Gulf Cooperation Council countries. This study presents a multimodal treatment protocol incorporating radiotherapy to primary and metastatic sites, guided by PSMA PET/CT, combined with systemic therapy for non-metastatic pelvic node-positive and de novo low-volume metastatic prostate cancer. Methods: We conducted a retrospective cohort study of patients treated with radical radiotherapy doses (68 Gy/25 Fr or 78 Gy/39 Fr) to the prostate gland and gross pelvic disease, and SBRT (35-40 Gy/5 Fr) to distant bone metastases. All patients received LHRH agonists ± abiraterone/prednisone or enzalutamide. Results: Twenty-four consecutive patients were analyzed. The median age was 70.1 years (IQR, 65.7-77.7), the median baseline PSA was 27.9 ng/mL (IQR = 19.7-53.8), and median follow up was 24 months (IQR = 20.4-31.2). Clinical staging was cT3b in (46%), cT2 in (25%), cT4 in (17%), cT3a in (13%) of patients. Pelvic nodal involvement (cN1) was present in 91.7% of patients, while 54.1% had metastatic disease. Treatment was well tolerated. Acute toxicity was predominantly grade 1 genitourinary (GU) toxicity, occurring in 87.5% of patients, with grade 2 GU toxicity observed in 8.2% and no acute gastrointestinal (GI) toxicity. Late toxicity remained minimal, with grade 1 and grade 2 GU toxicity reported in 45.8% and 4.2% of patients, respectively, and no late GI toxicity. Mild systemic treatment-related toxicities were reported in 25% of patients, including sexual dysfunction, hypokalemia, muscle weakness, osteoporosis and depression/anxiety. At the six-month follow-up PSMA PET/CT assessment, 85.7% achieved a complete metabolic response, and 14.2% achieved a partial response. Biochemically, 75% of patients achieved undetectable PSA levels (<0.01 ng/mL), with all patients achieving a PSA nadir < 0.2 ng/mL. Conclusions: This first, hypothesis-generating real-world experience from the GCC, suggests that an integrated approach combining systemic therapy with metastasis-directed therapy is feasible. Prospective randomized studies are required to validate these results.
Women have poorer survival rates in advanced, metastatic, or muscle-invasive bladder cancer (MIBC) than men. Enfortumab vedotin (EV) has changed the therapy and outcomes of MIBC and advanced bladder cancer dramatically. Therefore, the primary aim of this systematic review and meta-analysis was to evaluate sex-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), and overall survival (OS) in those patients. In October 2025, we performed a systematic literature search using MEDLINE via PubMed, Embase, and Cochrane Library. This study was prospectively registered at PROSPERO (CRD420251064260). The detailed review protocol is accessible via CRD. The systematic literature search identified 249 studies, of which 17 fulfilled the inclusion criteria. No significant sex-specific difference was observed for OS (10 studies; hazard ratio [HR] 0.88; 95% confidence interval [CI], 0.73-1.06; P = .17; I² = 32%). For PFS (8 studies), female sex was associated with a significantly better outcome (HR 0.67; 95% CI, 0.57-0.78; P < .001; I² = 0%). Because the funnel plot suggested a significant publication bias, we conducted adjustment analyses, which yielded an HR of 0.41 (95% CI, 0.24-0.57; P < .001). Only limited data were available for DFS, CSS, and EFS. Overall, the risk of bias was assessed as moderate. There is very limited evidence that women have a significantly better PFS than men during treatment with EV for bladder cancer. Further studies should incorporate explicit sex-specific analyses, eg, hormonal levels or genetic aspects, which are needed.
There is considerable uncertainty regarding the optimum approaches to target volume and organ at risk (OAR) delineation and tolerances to reirradiation for locally recurrent prostate cancer. To address these uncertainties, we undertook a literature review of treatment planning approaches of stereotactic body radiotherapy (SBRT) or brachytherapy reirradiation in published and ongoing prospective studies. Twenty published and 11 ongoing studies were identified. No phase 3 clinical trials were identified. Both focal and whole gland with/without simultaneous integrated boost approaches to target volume delineation were used. SBRT dose-fractionation schedules ranged from 25 to 42.5Gy in 5 fractions and 36-38Gy in 6 fractions with varying approaches to target objectives. Brachytherapy studies utilised both low dose rate and high dose rate approaches and employed a range of dose-fractionation schedules. Approaches to OAR delineation and constraints were heterogenous. No published and only 1 ongoing study utilises cumulative OAR constraints. Acceptable rates of genitourinary and gastrointestinal toxicities were observed in the majority of studies although some studies reported relatively high rates of severe toxicity events. The relatively short follow-up of some published series may underestimate the incidence of late toxicities. There remains uncertainty regarding optimum dose-fractionation schedules, target volumes and OAR constraints and how these influence toxicity. Prostate reirradiation using SBRT or brachytherapy can be used for treatment of locally recurrent prostate cancer. Treatment is recommended within prospective studies or registries with robust target definition, treatment delivery and comprehensive assessment of toxicity so that evidence to optimise treatment can be generated.
Variant histology (VH) bladder cancer is characterized by aggressive biology and adverse outcomes; however, evidence in the robot-assisted radical cystectomy (RARC) era remains limited. We evaluated oncologic outcomes following RARC for VH using propensity score matching (PSM) in a multi-institutional cohort. We retrospectively analyzed 280 patients who underwent RARC at 5 institutions (January 2018-November 2024); 60 had VH, and 220 had pure urothelial carcinoma (PUC). Using 11 pretreatment covariates (including institution, smoking status, and comorbidities), 1:1 nearest-neighbor matching (caliper 0.10) yielded 51 matched pairs. The primary endpoint was perioperative and pathologic outcomes. Adjuvant therapy use was recorded as a descriptive measure. Disease-free (DFS), cancer-specific (CSS), and overall survival (OS) were exploratory endpoints. Before matching, VH was associated with more advanced clinical stage and significantly worse unadjusted DFS, CSS, and OS. After expanded PSM, baseline characteristics were well balanced. The VH group retained significantly higher rates of ≥ pT3 disease (68.6% vs. 37.3%, P = .003) and transfusion (29.4% vs. 9.8%, P = .025); operative time, blood loss, complications, and hospital stay were comparable. Adjuvant therapy use was more frequent in the VH group (37.3% vs. 9.8%, P = .002). On exploratory Cox analysis, VH remained independently associated with significantly worse DFS, CSS, and OS (hazard ratios 2.3-2.8; all P < .05) after expanded adjustment. In this multi-institutional RARC cohort, after PSM for an expanded set of pretreatment clinical and comorbidity factors, perioperative outcomes other than transfusion rate were comparable between VH and PUC, supporting RARC as a feasible surgical approach for VH. However, VH retained significantly higher rates of ≥ pT3 disease, and exploratory survival analysis showed persistently worse DFS, CSS, and OS despite a greater use of adjuvant therapy, indicating that the adverse oncologic behavior of VH is not fully explained by pretreatment factors. Close postoperative surveillance and multimodal systemic therapy remain essential.