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1.
Int J Cancer ; 151(11): 2004-2011, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-35603905

RESUMEN

Despite treatment with cisplatin-based chemotherapy and surgical resection, clinical outcomes of patients with locally advanced urothelial carcinoma (UC) remain poor. We compared neoadjuvant/induction platinum-based combination chemotherapy (NAIC) with combination immune checkpoint inhibition (cICI). We identified 602 patients who attended our outpatient bladder cancer clinic in 2018 to 2019. Patients were included if they received NAIC or cICI for cT3-4aN0M0 or cT1-4aN1-3M0 UC. NAIC consisted of cisplatin-based chemotherapy or gemcitabine-carboplatin in case of cisplatin-ineligibility. A subset of patients (cisplatin-ineligibility or refusal of NAIC) received ipilimumab plus nivolumab in the NABUCCO-trial (NCT03387761). Treatments were compared using the log-rank test and propensity score-weighted Cox regression models. We included 107 Stage III UC patients treated with NAIC (n = 83) or cICI (n = 24). NAIC was discontinued in 11 patients due to progression (n = 6; 7%) or toxicity (n = 5; 6%), while cICI was discontinued in 6 patients (25%) after 2 cycles due to toxicity (P = .205). After NAIC, patients had surgical resection (n = 50; 60%), chemoradiation (n = 26; 30%), or no consolidating treatment due to progression (n = 5; 6%) or toxicity (n = 2; 2%). After cICI, all patients underwent resection. After resection (n = 74), complete pathological response (ypT0N0) was achieved in 11 (22%) NAIC-patients and 11 (46%) cICI-patients (P = .056). Median (IQR) follow-up was 26 (20-32) months. cICI was associated with superior progression-free survival (P = .003) and overall survival (P = .003) compared to NAIC. Our study showed superior survival in Stage III UC patients pretreated with cICI if compared to NAIC. Our findings provide a strong rationale for validation of cICI for locally advanced UC in a comparative phase-3 trial.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Carcinoma de Células Transicionales/tratamiento farmacológico , Cisplatino , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Ipilimumab/uso terapéutico , Terapia Neoadyuvante , Nivolumab/uso terapéutico , Platino (Metal)/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología
2.
World J Urol ; 40(5): 1167-1174, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35218372

RESUMEN

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Vejiga Urinaria , Vacuna BCG/uso terapéutico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Cistectomía , Femenino , Humanos , Inmunoterapia , Masculino , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía
3.
World J Urol ; 40(11): 2707-2715, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36169695

RESUMEN

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.


Asunto(s)
Cistectomía , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Terapia Neoadyuvante/métodos , Cisplatino/uso terapéutico , Carboplatino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Músculos , Estudios Retrospectivos , Gemcitabina
4.
Curr Opin Urol ; 30(5): 654-664, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32701719

RESUMEN

PURPOSE OF REVIEW: In this narrative review, we assessed the role of F-fluoro-2-deoxy-D-glucose-positron emission tomography/CT (FDG-PET/CT) in preoperative staging and response evaluation of neoadjuvant chemotherapy in muscle-invasive bladder carcinoma (MIBC), and to assess its incremental value to contrast-enhanced (CE)CT and MRI in terms of patient management at initial diagnosis and detection of recurrence. RECENT FINDINGS: A literature search in PubMed yielded 46 original reports, of which 15 compared FDG-PET/CT with CECT and one with MRI. For primary tumor assessment, FDG-PET/CT proved not accurate enough (13 reports; n = 7-70). For lymph node assessment, sensitivity of FDG-PET/CT is superior to CT with comparable specificity in 19 studies (n = 15-233). For detection of distant metastases, data from eight studies (n = 43-79) suggests that FDG-PET/CT is accurate, although comparative studies are lacking. Limited evidence (four studies, n = 19-50) suggests that FDG-PET/CT is not accurate for response evaluation of neoadjuvant chemotherapy. FDG-PET/CT incited change(s) in patient management in 18-68% of patients (five reports; n = 57-103). For detection of recurrence, seven studies (n = 29-287) indicated that FDG-PET/CT is accurate. SUMMARY: Most studies evaluated FDG-PET/CT for lymph node assessment and reported higher sensitivity than CT, with comparable specificity. FDG-PET/CT showed incremental value to CECT for recurrence and often incited change(s) in patient management.


Asunto(s)
Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Músculos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Cistectomía , Fluorodesoxiglucosa F18 , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática/patología , Músculos/patología , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Radiofármacos , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/patología
6.
J Clin Med ; 12(10)2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37240473

RESUMEN

Occult lymph node (LN)-metastases are frequently found after upfront radical cystectomy (uRC) for bladder cancer (BC). We evaluated whether the implementation of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) influenced nodal staging at uRC. All consecutive BC patients who underwent uRC with bilateral pelvic lymph node dissection (PLND) were identified and divided into two cohorts: cohort A consisted of patients staged with FDG PET/CT and contrast-enhanced CT (CE-CT) (2016-2021); cohort B consisted of patients staged with CE-CT only (2006-2011). The diagnostic performance of FDG PET/CT was assessed and compared with that of CE-CT. Thereafter, we calculated the occult LN metastases proportions for both cohorts. In total, 523 patients were identified (cohort A n = 237, and cohort B n = 286). Sensitivity, specificity, PPV and NPV of FDG PET/CT for detecting LN metastases were 23%, 92%, 42%, and 83%, respectively, versus 15%, 93%, 33%, 81%, respectively, for CE-CT. Occult LN metastases were found in 17% of cohort A (95% confidence interval (CI) 12.2-22.8) and 22% of cohort B (95% CI 16.9-27.1). The median size of LN metastases was 4 mm in cohort A versus 13 mm in cohort B. After introduction of FDG PET/CT, fewer and smaller occult LN metastases were present after uRC. Nevertheless, up to one-fifth of occult (micro-)metastases were still missed.

7.
Bladder Cancer ; 9(1): 49-57, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38994487

RESUMEN

BACKGROUND: Neoadjuvant/induction chemotherapy (NAIC) improves survival in patients with muscle-invasive bladder carcinoma (MIBC). On-treatment response assessment may aid in decisions to continue or cease NAIC. OBJECTIVE: We investigated whether 18F-fluoro-2-deoxy-D-glucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) could predict response to NAIC and compared to contrast-enhanced Computed Tomography (CECT). METHODS: We prospectively included 83 patients treated for MIBC (i.e. high-risk cT2-4N0M0 or cT1-4N+M0-1a) between 2014 and 2018. Response to NAIC was assessed after 2-3 cycles with FDG-PET/CT (Peter-Mac and EORTC criteria) and CECT (RECIST1.1 criteria). We assessed prediction of complete pathological response (pCR; ypT0N0), complete pathological down-staging (pCD;≤ypT1N0), any down-staging from baseline (ypTN < cTN) and progression (inoperable tumor/ypN+/M+). The reference standard was histopathological assessment or clinical follow-up. Sensitivity, specificity, and accuracy were calculated. RESULTS: Pathological response rates were 21% for pCR, 29% for pCD, and 10% progressed. All patients underwent FDG-PET/CT and 61 patients also underwent CECT (73%). Accuracy of FDG-PET/CT for prediction of pCR, pCD, and progression were 73%, 48%, and 73%, respectively. Accuracy of CECT for prediction of pCR, pCD, and progression were 78%, 65%, and 67%, respectively. Specificity of CECT was significantly higher than FDG-PET/CT for prediction of pCD and any down-staging (p = 0.007 and p = 0.022). In all other analyses, no significant differences between FDG-PET/CT and CECT were found. CONCLUSIONS: Routine FDG-PET/CT has insufficient predictive power to aid in response assessment compared to CECT.

8.
Eur Urol Oncol ; 5(3): 366-369, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33583752

RESUMEN

Given the high risk of systemic relapse following initial therapy for muscle-invasive bladder cancer (MIBC), improved pretreatment staging is needed. We evaluated the incremental value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) after standard conventional staging, in the largest cohort of MIBC patients to date. This is a retrospective analysis of 711 consecutive patients with invasive urothelial bladder cancer who underwent staging contrast-enhanced CT (chest and abdomen) and FDG-PET/CT in a tertiary referral center between 2011 and 2020. We recorded the clinical stage before and after FDG-PET/CT and treatment recommendation based on the stage before and after FDG-PET/CT. Clinical stage changed after FDG-PET/CT in 184/711 (26%) patients. Consequently, the recommended treatment strategy based on imaging changed in 127/711 (18%) patients. In 65/711 (9.1%) patients, potential curative treatment changed to palliative treatment because of the detection of distant metastases by FDG-PET/CT. Fifty (7.0%) patients were selected for neoadjuvant/induction chemotherapy based on FDG-PET/CT. Moreover, FDG-PET/CT detected lesions suspicious for second primary tumors in 15%; a second primary malignancy was confirmed in 28/711 (3.9%), leading to treatment change in ten (1.4%) patients. Contrarily 57/711 (8.1%) had false positive secondary findings. In conclusion, FDG-PET/CT provides important incremental staging information, which potentially influences clinical management in 18% of MIBC patients, but leads to false positive results as well. PATIENT SUMMARY: In this report, we investigated the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scanning on treatment of bladder cancer patients. We found that FDG-PET/CT potentially influences the treatment of almost one-fifth of patients. We therefore suggest performing FDG-PET/CT as part of bladder cancer staging.


Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias de la Vejiga Urinaria , Humanos , Metástasis Linfática , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/terapia
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