Browsing by Subject "Urothelial carcinoma"

Now showing 1 - 4 of 4
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    Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter
    (Sage, 2019-01-08) Bianconi, Maristella; Cimadamore, Alessia; Faloppi, Luca; Scartozzi, Mario; Santoni, Matteo; Lopez-Beltran, Antonio; Cheng, Liang; Scarpelli, Marina; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
    Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1-2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15-60%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.
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    Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)
    (BMC, 2021-05-24) Grivas, P.; Loriot, Y.; Morales-Barrera, R.; Teo, M. Y.; Zakharia, Y.; Feyerabend, S.; Vogelzang, N.J.; Grande, E.; Adra, N.; Necchi, A.; Rodriguez-Vida, A.; Gupta, S.; Josephs, D.H.; Srinivas, S.; Wride, K.; Thomas, D.; Simmons, A.; Loehr, A.; Dusek, R.L.; Nepert, D.; Chowdhury, S.; Medicine, School of Medicine
    Background: ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). Methods: Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. Results: Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. Conclusions: Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.
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    Narrative review: update on immunotherapy and pathological features in patients with bladder cancer
    (AME Publishing, 2021-03) Aurilio, Gaetano; Cimadamore, Alessia; Lopez-Beltran, Antonio; Scarpelli, Marina; Massari, Francesco; Verri, Elena; Cheng, Liang; Santoni, Matteo; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
    Over the last few years efficacy of immunotherapy using immune checkpoint inhibitors (ICI) has been investigated in patients with bladder cancer (BC) at all stages. The present article aims to assess new therapeutic options with emerging agents in BC patients, shedding light on ICI-based treatments encompassing all disease stages, from non-muscle invasive (NMIBC) to muscle-invasive (MIBC) BC, concluding with metastatic MIBC. In bacillus Calmette-Guerin (BCG) unresponsive patients with carcinoma in situ, pembrolizumab has been recently approved. In the neoadjuvant setting, results from two clinical trials seem to identify pathological and genomic features of highly responsive tumors. Squamous cells and lymphoepithelioma/like histotypes, programmed cell-death ligand 1 (PD-L1) expression and high levels of activate T cells have been associated with higher response rate. In the metastatic setting, only 30% of patient may respond to ICI. A panel of biomarkers for patient selection is an actual need since the correlation between response and PD-L1 expression seem inconsistent across clinical trials, with some exceptions. Molecular characterization of BC, tumor mutation burden and immune-gene expression profiling might introduce new molecular biomarkers, hopefully transferable into the clinical-pathological practice.
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    Urine Cytology in Patients with Gender Confirmation Surgery and Hormone Therapy: Evaluation of Urine Cytology Performance in an Underserved Patient Population
    (Elsevier, 2023-07-01) Khorsandi, Nikka; Ding, Chien-Kuang Cornelia; VandenBussche , Christopher J.; Verduzco, Carlo De la Sancha; Greenland, Nancy; Vohra, Poonam; Pathology and Laboratory Medicine, School of Medicine
    Introduction: There is a practice gap and educational need regarding urine cytology (UC) performance in patients with history of gender confirmation surgery (GCS) and/or hormone therapy (HT). This potentially impacts diagnostic accuracy in this medically underserved population. We report a methodology that identifies relevant cases and evaluates the performance of UC in this cohort. Materials and methods: Two institutional pathology archives from 2000 to 2021 were searched using relevant keywords to identify UC specimens from patients with GCS and/or HT for this retrospective study. For each specimen, patient demographics, relevant clinical history, and history of HT and/or GCS were noted. Each case was blindly reviewed by a cytopathologist according to The Paris System. Results: A total of 32 UC specimens from 15 patients with history of GCS and/or HT were identified. There were 13 male to female and 2 female to male transgender patients. The original diagnosis was negative for high-grade urothelial carcinoma (NHGUC) in 24 of 32 (75%) and atypical urothelial cells (AUC) in 8 of 32 (25%) cases. The most common atypical features were irregular nuclear membranes and prominent small nucleoli in 7 of 8 (87.5%). Degenerative changes were present in 5 of 8 (62.5%). On re-review, with relevant clinical history, 100% of cases were re-classified as NHGUC. Conclusions: The original diagnosis of AUC in these cases likely reflects reactive changes post GCS and/or HT. This cohort may be at risk of AUC overdiagnosis, particularly if the pathologist is unaware of this clinical history. Pathologists need to recognize reactive cytomorphologic changes in these patients. Further multi-institutional studies are warranted to expand knowledge about UC performance in these patients.