Urologic Oncology-seminars and Original Investigations最新文献

{"title":"Perioperative and survival outcomes of synchronous vs. metachronous upper tract urothelial carcinoma among bladder cancer patients treated with radical cystectomy and nephroureterectomy: Results from an International Multicenter Collaborative Study-On behalf of the Young Academic Urology (YAU) Urothelial Working Group.","authors":"Roberta Corvino, Giuseppe Basile, Valerio Santarelli, Vincenzo Asero, Ettore De Berardinis, Alessandro Sciarra, Luigi Vittori, Yasmin Abu-Ghanem, Rajesh Nair, Muhammad Shamim Khan, Ramesh Thurairaja, Ravi Barod, Wojciech Krajewski, Jan Laszkiewicz, Simone Albisinni, Keiichiro Mori, Felix Guerrero-Ramos, David D'Andrea, Andrea Gallioli, Ekaterina Laukhtina, Agata Suleja, Elisabeth Grobet-Jeandin, Andrea Mari, Laura S Mertens, Marco Moschini, Mario De Angelis, Pietro Scillipoti, Francesco Soria, Alessandro Bosio, Jeremy Teoh, Francesco Claps, Antonio Amodeo, Aleksander Ślusarczyk, Roberto Contieri, Daniel Subiela, Ana Tagalos, Karl H Tully, Renate Pichler, Alessandro Antonelli, Riccardo Bertolo, Alessandro Veccia, Sarah Malandra, Rodolfo Hurle, Francesco Sormani, Felice Crocetto, Roman Mayr, Angelo Porreca, Giuseppe Simone, Gabriele Tuderti, Bernardo Rocco, Alchiede Simonato, Franco Alchiede Simonato, Gautier Marcq, Paolo Gontero, Zhe Tian, Pierre Karakiewicz, Benjamin I Chung, Benjamin Pradere, Francesco Del Giudice","doi":"10.1016/j.urolonc.2026.08.007","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.08.007","url":null,"abstract":"<p><strong>Background and objective: </strong>Patients undergoing radical cystectomy (RC) for bladder cancer may present with synchronous or metachronous upper tract urothelial carcinoma (UTUC). These scenarios may differ in oncological outcomes and surgical complexity. This study sought to compare oncologic and perioperative outcomes in patients undergoing RC and radical nephroureterectomy (RNU) for synchronous or metachronous UTUC.</p><p><strong>Methods: </strong>Data from 23 tertiary referral centers were retrospectively collected (2002-2024). Perioperative outcomes included length of stay (LOS) and complications (Clavien-Dindo classification). Disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were estimated from RC using Kaplan-Meier and landmark analysis. Multivariable Cox regression modeling identified predictors of DFS and OS and explored the impact of RNU timing on oncological outcomes.</p><p><strong>Key findings and limitations: </strong>Among 177 RC patients (n = 142 [80%] males), 106 (60%) underwent RNU subsequent to RC for metachronous UTUC. Concomitant RC and RNU led to longer LOS (10 vs. 7 days, P = 0.004), and statistically significant higher rate of major complications (Clavien-Dindo ≥ IIIa, 29.6% vs. 15.1%, P = 0.03). Metachronous disease showed better 60-month DFS (69.1% vs. 47.6%), CSS (80.3% vs. 66.4%) and OS (69.2% vs. 47.6%). Histological subtype at RNU independently predicted worse DFS (HR 2.64, P = 0.01) and OS (HR 3.22, P = 0.01), while metachronous presentation predicted better DFS (HR 0.36, P < 0.001) and OS (HR 0.53, P = 0.04). Limitations include the retrospective design and a relatively limited sample size.</p><p><strong>Conclusions and clinical implications: </strong>Synchronous panurothelial disease at diagnosis requiring RC and RNU is related to worse perioperative and survival outcomes compared to metachronous disease. Our results highlight the need for dedicated studies to define individualized treatment and surveillance strategies for this challenging patient population.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXD1 upregulates DARS2-mediated glycolysis to drive cisplatin resistance in bladder cancer.","authors":"Xianyong Li, Mingqiang Su, Jingxian Luo, Dengjun Han, Liangliang Qing, Dayong Zhang, Sheng Liu, Junfa Liu, Guangqing Fu","doi":"10.1016/j.urolonc.2026.07.027","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.07.027","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy remains the most effective systemic treatment for bladder cancer (BLCA), with cisplatin as the primary agent. However, the frequent development of cisplatin resistance limits its clinical efficacy. Forkhead box D1 (FOXD1) is implicated in BLCA progression, yet its role in mediating cisplatin resistance remains unexplored.</p><p><strong>Methods: </strong>FOXD1 expression and its correlation with patient prognosis in BLCA were analyzed using the TCGA database. Cisplatin-resistant BLCA cell lines (T24-R and HT-1376-R) were established by treatment with gradient concentrations of cisplatin. qRT-PCR and Western blot were performed to detect the expression levels of FOXD1, β-catenin, and Aspartyl-tRNA Synthetase 2 (DARS2). Cell viability, proliferation, cell cycle, and apoptosis were assessed using CCK-8, colony formation assays, and flow cytometry. Co-IP was performed to examine the interaction between FOXD1 and β-catenin. Glycolysis levels in BLCA cells were determined using specific assay kits.</p><p><strong>Results: </strong>FOXD1 was highly expressed in BLCA tissues and correlated with poor prognosis. Knockdown of FOXD1 inhibited proliferation and cell cycle progression, promoted apoptosis, and enhanced cisplatin sensitivity in T24-R cells, while reducing β-catenin nuclear translocation and DARS2 expression. Overexpression of FOXD1 exerted the opposite effects on HT-1376-R cells and increased DARS2 expression, which were reversed by β-catenin knockdown. Moreover, knockdown of TCFs/LEF suppressed DARS2 expression. DARS2 was enriched in the glycolysis pathway. Its overexpression promoted glycolysis, proliferation, and cell cycle progression, while inhibiting apoptosis and cisplatin sensitivity in HT-1376-R cells-effects were reversed by 2-DG.</p><p><strong>Conclusion: </strong>FOXD1 facilitates β-catenin nuclear translocation and upregulates DARS2 to enhance glycolysis, thereby promoting cisplatin resistance in BLCA. These findings identify the FOXD1/β-catenin/DARS2 axis as a potential therapeutic target for overcoming cisplatin resistance in BLCA clinically.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative indocyanine green fluorescence guidance to reduce ureteroenteric anastomotic strictures during robot-assisted radical cystectomy. A systematic review and meta-analysis.","authors":"Emmanuel Oberdá Nominato, Arthur Ávila Reis Roncarati Miranda, Maria Eduarda Martins Fernandes, Victor Lima Amaral, Angélica Steckelberg Pimenta Macedo, Kenzo Higashi Lima, Marcelo Albuquerque Barbosa Martins, Guilherme Canabrava Rodrigues Silva","doi":"10.1016/j.urolonc.2026.08.003","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.08.003","url":null,"abstract":"<p><p>Ureteroenteric anastomotic stricture (UAS) is a clinically relevant complication of robot-assisted radical cystectomy (RARC), primarily driven by ureteral ischemia. Indocyanine green (ICG) fluorescence has been proposed to identify ischemic segments prior to anastomosis. This systematic review and meta-analysis aimed to evaluate UAS incidence with ICG versus no ICG during RARC. PubMed, Embase, and Cochrane were searched up to February 2026. Eligible studies were comparative observational studies on adults undergoing RARC exclusively. Random-effects models were used to pool risk ratios (RR) and mean differences (MD) with 95% confidence intervals. Four observational studies were included (n = 886 patients; 1,739 ureters): 369 (41.6%) underwent ICG - guided assessment and 517 (58.4%) standard assessment without ICG. Pooled analysis showed no statistically significant reduction in UAS per ureter (RR 0.31, 95% CI 0.08-1.16; P = 0.08; I² = 76.4%). Sensitivity analysis excluding the highest-bias study eliminated heterogeneity and shifted results in favor of ICG (RR 0.20, 95% CI 0.09-0.46; I² = 0%), suggesting that the primary pooled estimate is unstable and heavily influenced by between-study heterogeneity. No significant differences were observed in ureteral excision length, node positivity, or operative time. Current evidence is limited to non-randomized studies with serious risk of bias and very low certainty. The instability of the pooled estimate highlights the inadequacy of the current evidence base and the need for prospective randomized studies to define the true clinical benefit of ICG. PROSPERO: CRD420261322254.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic landscape of upper tract urothelial carcinoma: Intraluminal agents, perioperative chemotherapy, and immunotherapy.","authors":"Sri Saran Manivasagam, Jay D Raman","doi":"10.1016/j.urolonc.2026.08.002","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.08.002","url":null,"abstract":"<p><strong>Background: </strong>Upper tract urothelial carcinoma (UTUC) is an uncommon genitourinary malignancy with distinct anatomical and clinical challenges. Historically, treatment strategies have been extrapolated from bladder cancer, leaving gaps in evidence for UTUC-specific management. Recent advances in intraluminal drug delivery and systemic therapy have presented new options across localized, locally advanced, and metastatic disease.</p><p><strong>Methods: </strong>We reviewed prospective trials, retrospective cohort studies, and ongoing studies evaluating intraluminal chemo-ablative agents, perioperative chemotherapy, immunotherapy, and targeted therapies for UTUC. Outcomes of efficacy, safety, and innovation in drug delivery systems were synthesized.</p><p><strong>Results: </strong>Kidney-sparing approaches for localized UTUC have advanced with intraluminal chemoablation. UGN-101, a mitomycin-C containing reverse-thermal gel, demonstrated meaningful complete response rates and durable remission, while mitomycin-C (aqueous) and Bacillus Calmette-Guérin-based regimens showed variable efficacy. Novel delivery systems, including reverse-thermal gels and biodegradable drug-eluting stents, aim to improve drug dwell time and reduce recurrence. For high-risk localized disease, adjuvant platinum-based chemotherapy significantly improved disease-free survival and is now standard of care. Neoadjuvant chemotherapy offers long-term survival benefits and preserves eligibility for cisplatin. Immunotherapy has emerged perioperatively, with adjuvant checkpoint inhibitors improving disease-free survival and ongoing trials exploring chemo-immunotherapy combinations. In metastatic UTUC, antibody-drug conjugates combined with immunotherapy have demonstrated superior progression-free and overall survival compared with chemotherapy. Targeted therapies, such as FGFR inhibitors, provide additional options for biomarker-selected patients.</p><p><strong>Conclusions: </strong>UTUC management is evolving towards stage-specific strategies integrating chemoablation, systemic therapy, and molecularly guided approaches. Future priorities include randomized trials, optimized drug delivery, and long-term safety evaluation.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technical requirements and platform considerations for molecular residual disease in genitourinary tumors.","authors":"Jong Taek Kim","doi":"10.1016/j.urolonc.2026.07.022","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.07.022","url":null,"abstract":"<p><p>Liquid biopsy ctDNA testing is becoming an essential part of cancer patient care. Many types of molecular assays for ctDNA MRD or ctDNA profiling are available. They differ in methodology, can be targeted vs. nontargeted, and tumor-informed vs. tumor-uninformed. There are technical benefits and pitfalls that come with each type of ctDNA assays. Factors such as level of detection, turnaround time, cost/reimbursement, and tumor indication may play a role in picking the most appropriate test. Given there are many available ctDNA MRD testing assays available, this paper will provide technical reviews of various methods and analytical qualifications of various ctDNA MRD detection assays.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmet needs in penile cancer: Review and perspectives from the Global Society of Rare Genitourinary Tumors.","authors":"Luis G Medina, Salvador Jaime-Casas, Federico Eskenazi, Juan Dugarte, Jad Chahoud, Philippe E Spiess","doi":"10.1016/j.urolonc.2026.06.003","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.06.003","url":null,"abstract":"<p><p>Penile cancer is an uncommon yet aggressive disease, especially at advanced stages. Management can be morbid, and patients often face a significant psychosocial impact alongside a lack of patient advocacy/support system in most parts of the globe. Local treatments can preserve penile function and provide acceptable oncologic control in selected patients. The use of organ-sparing treatments is higher in experienced centers, where adherence to guidelines is greater. Inguinal lymph node dissection remains essential in the management of this disease as it is both diagnostic and therapeutic. Several modifications to the initially described technique have been proposed with the intention of decreasing the morbidity of this procedure, which is approximately 30% for all comers. However, lack of standardization on the complication reporting and limited high-quality evidence further hinders progress in this field. For locally advanced and metastatic disease, the combination of paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy is the gold standard. However, this regimen offers limited benefit in advanced stages. In contrast, chemoimmunotherapy and other systemic therapies show promising results in a few small prospective, single-arm trials several of which are still under investigation. The objective of this manuscript is to synthesize evidence on the 4 main unment needs in penile cancer: patient advocacy/quality of life, local/organ-sparing treatment, inguinal lymph node dissection (ILND), and systemic therapy, highlighting gaps in clinical care and research priorities. A focused effort in those areas is needed to advance further patient care, quality of life, and their ability to navigate this disease.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing testicular cancer therapy: Survivorship perspectives on reducing late toxicities without compromising outcomes.","authors":"Kai Wen Cheng, Jersey-Kate Castillo, Antoin Douglawi, Martin Hofmann, Herbert C Ruckle, Gagan Prakash, Brian Hu, Muhannad Alsyouf","doi":"10.1016/j.urolonc.2026.05.021","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.05.021","url":null,"abstract":"<p><p>Testicular cancer is the most common malignancy in young men with excellent survival rates. However, this success is associated with significant treatment-related toxicities. This review explores the current landscape of testicular cancer management, focusing on strategies to minimize long-term morbidity while maintaining oncologic efficacy. We reviewed contemporary literature and clinical trial data concerning treatment-related burdens (chemotherapy, radiation, and surgery), advancements in surgical techniques, novel biomarkers, and evolving surveillance protocols. Conventional therapies like platinum-based chemotherapy and radiotherapy are associated with dose-dependent toxicities, including cardiovascular disease, ototoxicity, and secondary malignancies. In contrast, retroperitoneal lymph node dissection (RPLND) offers a curative option with minimal long-term systemic toxicity albeit surgical risks. Recent trials (surgery in early metastatic seminoma [SEMS], COTRIMS, Primetest) demonstrate that primary RPLND in Stage II seminoma can significantly reduce the cumulative need for chemotherapy. Furthermore, surgical refinements such as the midline extraperitoneal approach and robotic-assisted techniques have reduced perioperative morbidity and hospital stays. The emergence of microRNA-371 as a potential sensitive biomarker shows promise in identifying micrometastatic disease, monitoring treatment response, and reducing surgical overtreatment for benign pathology. Finally, trials like TRISST and WATChmAN support less intensive surveillance through magnetic resonance imaging (MRI), reduced imaging frequency, and telehealth. The paradigm of testicular cancer care is shifting toward emphasis on toxicity reduction. By integrating advanced surgical techniques, de-escalated systemic therapies, and biology-based decision-making through novel biomarkers, clinicians can optimize survivorship outcomes without compromising oncologic outcomes in this young patient population.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare genitourinary cancers: Spotlight on an unmet need in urologic oncology.","authors":"Benjamin T Ristau, Philippe E Spiess","doi":"10.1016/j.urolonc.2026.04.289","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.04.289","url":null,"abstract":"","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary management of adrenocortical carcinoma: A narrative review.","authors":"Ankit Misra, Aditya Phadte, Vasanthapriya Subramani, Aditya Dhanawat, Santosh Menon, Amandeep Arora, Ramya Nagarajan, Priyamvada Maitre, Mahendra Pal, Amit Joshi, Anurag Lila, Gagan Prakash, Vedang Murthy","doi":"10.1016/j.urolonc.2026.04.010","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.04.010","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy arising from the adrenal cortex, characterized by local invasion and frequent distant metastases. Tumor size is a key predictor of malignancy, with lesions larger than 4 cm carrying a high likelihood of being malignant. Subsets of ACCs are functional, secreting excess glucocorticoids, sex steroids, or mineralocorticoids, leading to characteristic clinical syndromes. Diagnosis is often delayed due to nonspecific presentations, and management remains challenging because of limited effective systemic therapies, high recurrence rates, and the rarity of the disease, which restricts large-scale clinical trials. This review provides an overview of the current strategies in the diagnosis, staging, and treatment of ACC, and discusses the evolving therapeutic modalities. A narrative literature review was conducted using relevant publications from PubMed, Scopus, and recent international guidelines. Data from key trials and consensus statements were incorporated. Complete surgical resection, which entails adrenalectomy with local lymph node dissection, is the mainstay of curative treatment. Adjuvant mitotane and radiation therapy are currently the cornerstone of treatment post-surgery in those with high-risk features. High-risk tumors are those with incomplete resection, high grade, and Ki67>10%. Studies are ongoing to determine the role of chemotherapy in the adjuvant setting. The etoposide-doxorubicin-cisplatin (EDP) regimen, combined with mitotane, is the current standard of care for advanced disease. New therapies targeting tumor genomics or the immune microenvironment are under investigation. Adrenocortical carcinoma management requires a multidisciplinary and individualized approach. Further research into molecular and immunotherapeutic strategies is needed to improve patient outcomes.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147933935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urethral cancer management in contemporary practice: A review.","authors":"Herney Andrés García-Perdomo, Angélica María Dávila-Raigoza, Philippe E Spiess","doi":"10.1016/j.urolonc.2026.04.006","DOIUrl":"https://doi.org/10.1016/j.urolonc.2026.04.006","url":null,"abstract":"<p><p>Primary urethral carcinoma (PUC) is a very rare and aggressive genitourinary cancer. Its low incidence has limited the availability of clinical trials and robust information, with most evidence derived from retrospective series, population-based registries, and expert consensus. This review synthesizes contemporary knowledge on epidemiology, diagnosis, histopathology, molecular biology, treatment, and future perspectives in PUC. Sex-specific and anatomical differences strongly influence presentation and histology: squamous cell carcinoma predominates in men with distal disease, urothelial carcinoma is more frequent in the prostatic urethra, and adenocarcinoma arises mainly from female periurethral diverticula. Chronic inflammation, strictures, long-term catheterization, and human papillomavirus infection are established etiologic factors. Diagnostic delays are common, particularly in women, underscoring the need for heightened suspicion, early biopsy, and advanced imaging for accurate staging. Surgical resection remains the cornerstone for localized disease, with penile- or urethra-preserving approaches favored in distal tumors to optimize functional outcomes. Radical surgery, including penectomy or anterior exenteration, is often required in proximal or advanced cases but carries significant morbidity. Radiotherapy, historically applied in women and unfit surgical candidates, retains a role in organ preservation when combined with other therapies. Systemic treatment, centered on cisplatin-based regimens, has demonstrated improved survival in advanced disease, with neoadjuvant strategies enhancing resectability. Emerging evidence supports integrating immunotherapy and targeted agents guided by molecular alterations. Multimodal therapy has become the standard in advanced stages, improving survival while enabling functional preservation in selected patients. Prognosis is dictated by stage, nodal status, histology, and surgical margins. Future priorities include international collaborations, harmonized registries, biomarker-driven personalization, and integration of patient-reported outcomes to align oncologic control with quality of life. PUC management today is defined by risk-adapted, multidisciplinary strategies delivered in specialized centers, reflecting both historical lessons and modern advances.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}