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15 pages, 1000 KiB

Open AccessArticle

Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients with No Progression and with No More than Five Residual Metastatic Lesions Following First-Line Systemic Therapy: A Retrospective Analysis

by Amélie Aboudaram, Léonor Chaltiel, Damien Pouessel, Pierre Graff-Cailleaud, Nicolas Benziane-Ouaritini, Paul Sargos, Ulrike Schick, Gilles Créhange, Elizabeth Cohen-Jonathan Moyal, Christine Chevreau and Jonathan Khalifa

Cancers 2023, 15(4), 1161; https://doi.org/10.3390/cancers15041161 - 11 Feb 2023

Cited by 9 | Viewed by 2658

Abstract

Local consolidative radiotherapy in the treatment of metastatic malignancies has shown promising results in several types of tumors. The objective of this study was to assess consolidative radiotherapy to the bladder and to residual metastases in metastatic urothelial bladder cancer with no progression [...] Read more.

Local consolidative radiotherapy in the treatment of metastatic malignancies has shown promising results in several types of tumors. The objective of this study was to assess consolidative radiotherapy to the bladder and to residual metastases in metastatic urothelial bladder cancer with no progression following first-line systemic therapy. Materials/methods: Patients who received first-line therapy for the treatment of metastatic urothelial bladder cancer (mUBC) and who were progression-free following treatment with no more than five residual metastases were retrospectively identified through the database of four Comprehensive Cancer Centers, between January 2005 and December 2018. Among them, patients who received subsequent definitive radiotherapy (of EQD2Gy > 45Gy) to the bladder and residual metastases were included in the consolidative group (irradiated (IR) group), and the other patients were included in the observation group (NIR group). Progression-free survival (PFS) and overall survival (OS) were determined from the start of the first-line chemotherapy using the Kaplan–Meier method. To prevent immortal time bias, a Cox model with time-dependent covariates and 6-month landmark analyses were performed to examine OS and PFS. Results: A total of 91 patients with at least stable disease following first-line therapy and with no more than five residual metastases were analyzed: 51 in the IR group and 40 in the NIR group. Metachronous metastatic disease was more frequent in the NIR group (19% vs. 5%, p = 0.02); the median number of metastases in the IR group vs. in the NIR group was 2 (1–9) vs. 3 (1–5) (p = 0.04) at metastatic presentation, and 1 (0–5) vs. 2 (0–5) (p = 0.18) after completion of chemotherapy (residual lesions), respectively. Two grade 3 toxicities (3.9%) and no grade 4 toxicity were reported in the IR group related to radiotherapy. With a median follow up of 85.9 months (95% IC (36.7; 101.6)), median OS and PFS were 21.7 months (95% IC (17.1; 29.7)) and 11.1 months (95% IC (9.9; 14.1)) for the whole cohort, respectively. In multivariable analysis, consolidative radiotherapy conferred a benefit in both PFS (HR = 0.49, p = 0.007) and OS (HR = 0.47, p = 0.015) in the whole population; in the landmark analysis at 6 months, radiotherapy was associated with improved OS (HR = 0.48, p = 0.026), with a trend for PFS (HR = 0.57, p = 0.082). Conclusion: Consolidative radiotherapy for mUBC patients who have not progressed after first-line therapy and with limited residual disease seems to confer both OS and PFS benefits. The role of consolidative radiotherapy in the context of avelumab maintenance should be addressed prospectively. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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11 pages, 459 KiB

Open AccessArticle

Oncological Outcomes for Patients Harboring Positive Surgical Margins Following Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Retrospective Multicentric Study on Behalf of the YAU Urothelial Group

by Gautier Marcq, Luca Afferi, Yann Neuzillet, Timo Nykopp, Charlotte S. Voskuilen, Marc A. Furrer, Wassim Kassouf, Atiqullah Aziz, Anne Sophie Bajeot, Mario Alvarez-Maestro, Peter Black, Morgan Roupret, Aidan P. Noon, Roland Seiler, Kees Hendricksen, Mathieu Roumiguie, Karl H. Pang, Paul Laine-Caroff, Evanguelos Xylinas, Guillaume Ploussard, Marco Moschini and Paul Sargos Show full author list Hide full author list

Cancers 2022, 14(23), 5740; https://doi.org/10.3390/cancers14235740 - 22 Nov 2022

Cited by 11 | Viewed by 2484

Abstract

Introduction: Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival [...] Read more.

Introduction: Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) and identify predictors of each endpoint in patients with PSMs following RC for MIBC. Methods: A collaborative retrospective cohort study was conducted on 394 patients with PSMs who underwent RC for MIBC between January 2000 and December 2018 at 10 tertiary referral centers. Patients receiving perioperative radiotherapy were excluded from the study. Kaplan–Meier curves were used to estimate patient survival. Cox regression analysis was used to identify predictors of survival. Results: Median age at surgery was 70 years (IQR 62–76) with 129 (33%) and 204 (52%) patients had pT3 and pT4 tumors, respectively. Nodal metastasis (pN+) was identified in 148 (38%). Soft tissue PSMs were found in 283 (72%) patients, urethral PSMs in 65 (16.5%), and ureteral PSMs were found in 73 (18.5%). The median follow-up time was 44 months (95% CI 32–60). Median LRFS, MRFS, RFS, CSS, and OS were 14 (95% CI 11–17), 12 (95% CI 10–16), 10 (95% CI 8–12), 23 (95% CI 18–33), and 16 months (95% CI 12–19), respectively. On multivariable Cox regression analysis, the pT3–4 stage, pN+ stage, and multifocal PSMs were independent predictors of LRFS, MRFS, RFS, and OS. Adjuvant chemotherapy improved all oncological outcomes studied (p < 0.05). The number of lymph nodes removed was independently associated with better LRFS, MRFS, and RFS. Advanced age at diagnosis was independently associated with worse OS. Conclusion: Patients with PSMs following RC have poor outcomes since half of them will recur within a year and will die of their disease. Among all PSMs types, patients with multifocal PSMs harbor the worst prognosis. We observed a benefit of adjuvant chemotherapy, but clinical trials evaluating innovative adjuvant strategies for these patients remain an unmet need. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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16 pages, 1397 KiB

Open AccessArticle

Oncological Outcomes of Distal Ureterectomy for High-Risk Urothelial Carcinoma: A Multicenter Study by The French Bladder Cancer Committee

by Alexandra Masson-Lecomte, Victoire Vaillant, Mathieu Roumiguié, Stéphan Lévy, Benjamin Pradère, Michaël Peyromaure, Igor Duquesne, Alexandre De La Taille, Cédric Lebâcle, Adrien Panis, Olivier Traxer, Priscilla Leon, Maud Hulin, Evanguelos Xylinas, François Audenet, Thomas Seisen, Yohann Loriot, Yves Allory, Morgan Rouprêt and Yann Neuzillet

Cancers 2022, 14(21), 5452; https://doi.org/10.3390/cancers14215452 - 6 Nov 2022

Cited by 11 | Viewed by 2575

Abstract

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon disease and its gold-standard treatment is radical nephroureterectomy (RNU). Distal ureterectomy (DU) might be an alternative for tumors of the distal ureter but its indications remain unclear. Here, we aimed to evaluate the oncological [...] Read more.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon disease and its gold-standard treatment is radical nephroureterectomy (RNU). Distal ureterectomy (DU) might be an alternative for tumors of the distal ureter but its indications remain unclear. Here, we aimed to evaluate the oncological outcomes of DU for UTUC of the pelvic ureter. We performed a multicenter retrospective analysis of patients with UTUC who underwent DU. The primary endpoint was 5-year cancer-specific survival (CSS), followed by overall survival (OS), intravesical recurrence-free (IVR) and homolateral urinary tract recurrence-free (HUR) survivals as secondary endpoints. Univariate and multivariate Cox regressions were performed to assess factors associated with outcomes. 155 patients were included, 91% of which were high-risk. 5-year CSS was 84.4%, OS was 71.9%, IVR-free survival was 43.6% and HUR-free survival was 74.4%. Multifocality, high grade and tumor size were the most significant predictors of survival endpoints. Of note, neither hydronephrosis nor pre-operative diagnostic ureteroscopy/JJ stent were associated with any of the endpoints. Perioperative morbidity was minimal. In conclusion, DU stands as a possible alternative to RNU for UTUC of the pelvic ureter. Close monitoring is mandatory due to the high risk of recurrence in the remaining urinary tract. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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12 pages, 1952 KiB

Open AccessArticle

Radiomics for the Prediction of Overall Survival in Patients with Bladder Cancer Prior to Radical Cystectomy

by Piotr Woźnicki, Fabian Christopher Laqua, Katharina Messmer, Wolfgang Gerhard Kunz, Christian Stief, Dominik Nörenberg, Andrea Schreier, Jan Wójcik, Johannes Ruebenthaler, Michael Ingrisch, Jens Ricke, Alexander Buchner, Gerald Bastian Schulz and Eva Gresser

Cancers 2022, 14(18), 4449; https://doi.org/10.3390/cancers14184449 - 13 Sep 2022

Cited by 10 | Viewed by 2311

Abstract

(1) Background: To evaluate radiomics features as well as a combined model with clinical parameters for predicting overall survival in patients with bladder cancer (BCa). (2) Methods: This retrospective study included 301 BCa patients who received radical cystectomy (RC) and pelvic lymphadenectomy. Radiomics [...] Read more.

(1) Background: To evaluate radiomics features as well as a combined model with clinical parameters for predicting overall survival in patients with bladder cancer (BCa). (2) Methods: This retrospective study included 301 BCa patients who received radical cystectomy (RC) and pelvic lymphadenectomy. Radiomics features were extracted from the regions of the primary tumor and pelvic lymph nodes as well as the peritumoral regions in preoperative CT scans. Cross-validation was performed in the training cohort, and a Cox regression model with an elastic net penalty was trained using radiomics features and clinical parameters. The models were evaluated with the time-dependent area under the ROC curve (AUC), Brier score and calibration curves. (3) Results: The median follow-up time was 56 months (95% CI: 48–74 months). In the follow-up period from 1 to 7 years after RC, radiomics models achieved comparable predictive performance to validated clinical parameters with an integrated AUC of 0.771 (95% CI: 0.657–0.869) compared to an integrated AUC of 0.761 (95% CI: 0.617–0.874) for the prediction of overall survival (p = 0.98). A combined clinical and radiomics model stratified patients into high-risk and low-risk groups with significantly different overall survival (p < 0.001). (4) Conclusions: Radiomics features based on preoperative CT scans have prognostic value in predicting overall survival before RC. Therefore, radiomics may guide early clinical decision-making. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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18 pages, 1686 KiB

Open AccessArticle

Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer

by Elliott Diamant, Mathieu Roumiguié, Alexandre Ingels, Jérôme Parra, Dimitri Vordos, Anne-Sophie Bajeot, Emmanuel Chartier-Kastler, Michel Soulié, Alexandre de la Taille, Morgan Rouprêt and Thomas Seisen

Cancers 2022, 14(15), 3797; https://doi.org/10.3390/cancers14153797 - 4 Aug 2022

Cited by 6 | Viewed by 2284 | Correction

Abstract

Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and [...] Read more.

Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and divided into upfront and delayed groups, according to the receipt or not of BCG. Perioperative outcomes were evaluated and the impact of upfront vs. delayed eRC on pathological upstaging, defined as ≥pT2N0 disease at final pathology, was assessed using multivariable logistic regression. Recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS) were compared between upfront and delayed eRC groups using inverse probability of treatment weighting (IPTW)-adjusted Cox model. Results: Overall, 184 patients received either upfront (n = 87; 47%) or delayed (n = 97; 53%) eRC. No difference was observed in perioperative outcomes between the two treatment groups (all p > 0.05). Pathological upstaging occurred in 55 (30%) patients and upfront eRC was an independent predictor (HR = 2.65; 95% CI = (1.23–5.67); p = 0.012). In the IPTW-adjusted Cox analysis, there was no significant difference between upfront and delayed eRC in terms of RFS (HR = 1.31; 95% CI = (0.72–2.39); p = 0.38), CSS (HR = 1.09; 95% CI = (0.51–2.34); p = 0.82) and OS (HR = 1.19; 95% CI = (0.62–2.78); p = 0.60). Conclusion: our results suggest similar perioperative outcomes between upfront and delayed eRC, with an increased risk of upstaging after upfront eRC that did impact survival, as compared to delayed eRC. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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Review

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21 pages, 2622 KiB

Open AccessReview

Advances in Transversal Topics Applicable to the Care of Bladder Cancer Patients in the Real-World Setting

by Marga Garrido Siles, Antonio López-Beltran, Paula Pelechano, Ana María García Vicente, Regina Gironés Sarrió, Eva González-Haba Peña, Alfredo Rodríguez Antolín, Almudena Zapatero, José Ángel Arranz and Miguel Ángel Climent

Cancers 2022, 14(16), 3968; https://doi.org/10.3390/cancers14163968 - 17 Aug 2022

Cited by 2 | Viewed by 2514

Abstract

Recommendations regarding transversal topics applicable to bladder cancer patients independent of tumor grade and stage were established by members of the Spanish Oncology Genitourinary Multidisciplinary Working Group (SOGUG). Liquid biopsy in urine and blood samples is useful in the surveillance of non-muscle-invasive and [...] Read more.

Recommendations regarding transversal topics applicable to bladder cancer patients independent of tumor grade and stage were established by members of the Spanish Oncology Genitourinary Multidisciplinary Working Group (SOGUG). Liquid biopsy in urine and blood samples is useful in the surveillance of non-muscle-invasive and muscle-invasive bladder cancer, respectively. Multiparametric MRI is an accurate, faster and non-invasive staging method overcoming the understaging risk of other procedures. The combination of FDG-PET/MRI could improve diagnostic reliability, but definite criteria for imaging interpretation are still unclear. Hospital oncology pharmacists as members of tumor committees improve the safety of drug use. Additionally, safety recommendations during BCG preparation should be strictly followed. The initial evaluation of patients with bladder cancer should include a multidimensional geriatric assessment. Orthotopic neobladder reconstruction should be offered to motivated patients with full information of self-care requirements. Bladder-sparing protocols, including chemoradiation therapy and immune checkpoints inhibitors (ICIs), should be implemented in centers with well-coordinated multidisciplinary teams and offered to selected patients. The optimal strategy of treatment with ICIs should be defined from the initial diagnostic phase with indications based on scientific evidence. Centralized protocols combined with the experience of professional groups are needed for the integral care of bladder cancer patients. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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31 pages, 1840 KiB

Open AccessReview

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

by Soum D. Lokeshwar, Maite Lopez, Semih Sarcan, Karina Aguilar, Daley S. Morera, Devin M. Shaheen, Bal L. Lokeshwar and Vinata B. Lokeshwar

Cancers 2022, 14(11), 2578; https://doi.org/10.3390/cancers14112578 - 24 May 2022

Cited by 16 | Viewed by 6038

Abstract

Within the last forty years, seminal contributions have been made in the areas of bladder cancer (BC) biology, driver genes, molecular profiling, biomarkers, and therapeutic targets for improving personalized patient care. This overview includes seminal discoveries and advances in the molecular oncology of [...] Read more.

Within the last forty years, seminal contributions have been made in the areas of bladder cancer (BC) biology, driver genes, molecular profiling, biomarkers, and therapeutic targets for improving personalized patient care. This overview includes seminal discoveries and advances in the molecular oncology of BC. Starting with the concept of divergent molecular pathways for the development of low- and high-grade bladder tumors, field cancerization versus clonality of bladder tumors, cancer driver genes/mutations, genetic polymorphisms, and bacillus Calmette-Guérin (BCG) as an early form of immunotherapy are some of the conceptual contributions towards improving patient care. Although beginning with a promise of predicting prognosis and individualizing treatments, “-omic” approaches and molecular subtypes have revealed the importance of BC stem cells, lineage plasticity, and intra-tumor heterogeneity as the next frontiers for realizing individualized patient care. Along with urine as the optimal non-invasive liquid biopsy, BC is at the forefront of the biomarker field. If the goal is to reduce the number of cystoscopies but not to replace them for monitoring recurrence and asymptomatic microscopic hematuria, a BC marker may reach clinical acceptance. As advances in the molecular oncology of BC continue, the next twenty-five years should significantly advance personalized care for BC patients. Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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4 pages, 956 KiB

Open AccessCorrection

Correction: Diamant et al. Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer. Cancers 2022, 14, 3797

by Elliott Diamant, Mathieu Roumiguié, Alexandre Ingels, Jérôme Parra, Dimitri Vordos, Anne-Sophie Bajeot, Emmanuel Chartier-Kastler, Michel Soulié, Alexandre de la Taille, Morgan Rouprêt and Thomas Seisen

Cancers 2022, 14(23), 6001; https://doi.org/10.3390/cancers14236001 - 5 Dec 2022

Cited by 1 | Viewed by 1274

Abstract

In the original article [...] Full article

(This article belongs to the Special Issue Advance and New Insights in Bladder Cancer)

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