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- Palou, J., et al.
(författare)
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Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG : not as bad as previously thought
- 2018
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Ingår i: World journal of urology. - : SPRINGER. - 0724-4983 .- 1433-8726. ; 36:10, s. 1621-1627
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG.Methods: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model.Results:During a median follow-up of 5.2years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P<0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P<0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen.Conclusions: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.
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| 2. |
- Soria, Francesco, et al.
(författare)
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Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy
- 2018
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Ingår i: World journal of urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 36:11, s. 1775-1781
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG.Methods: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups.Results: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024)Conclusions: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.
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| 3. |
- Necchi, A., et al.
(författare)
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A phase III study of INCB054828 as adjuvant therapy in patients (pts) with high-risk urothelial carcinoma (UC) harboring fibroblast growth factor receptor 3 (FGFR3) genomic alterations
- 2018
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 328-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: After neoadjuvant chemotherapy (NAC), about 20% of pts with muscle-invasive UC are found to have advanced pT-stage or lymph node involvement and 5-year overall survival (OS) of them is < 30%. Tumor samples from these pts may provide information about chemotherapy resistance, and may predict for the activity of new drugs given postoperatively. Alterations of FGFR3 gene represent a therapeutic target in UC and FGFR3 mutations/fusions are enriched in UC Luminal-1 subtype. The pan-FGFR inhibitor INCB054828 has shown promising results in chemotherapy-treated patients with genomic alterations of FGFR3 in tumor tissue and is currently being evaluated in an international phase 2 study (fight-201, NCT02872714). Our study aims to assess the safety and efficacy of adjuvant INCB054828 in pts with FGFR3 mutations/fusions. Trial design: This is an open-label, single-arm, phase 2 study. Subjects will receive INCB054828 at a once-daily (QD) dose of 13.5 mg on a 2-weeks-on and 1-week-off schedule. Treatment should start within 60 days of surgery and will continue until 12 months, or until the evidence of disease recurrence or unacceptable toxicity onset. Key inclusion criteria are predominant UC histology, FGFR3 mutations/fusions (FoundationOne), bladder or upper tract UC, previous radical cystectomy or nephroureterectomy, previous administration ≥3 cycles of CDDP-based NAC, pT3-4 and/or pN1-3 stage. Relapse-free survival (RFS) is the primary endpoint, assessed every 9 weeks until disease recurrence or death. No interim analyses are planned. It is expected that about 30% of the total screened pts will harbor FGFR3 aberrations. In a single-stage design, with 90% power and one-sided alpha at 0.10, the total enrolled pts will be 56 (H0: 2-y RFS: 30%; H1: 2-y RFS: 45%). Translational research on tissue samples will include associations of immune-inflamed phenotype with next-generation sequencing results and outcome of treatment, and response to any subsequent immunotherapy. The study is sponsored by the EAU-Research Foundation and will involve 15 centers in Europe (EudraCT number 2017-004426-15). Clinical trial identification: EudraCT: 2017-004426-15.
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