European urology最新文献

Background and objective: Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy.

Methods: Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group. The outcome measures of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression estimated hazard ratios (HRs) for the three RFs and cN1 disease.

Key findings and limitations: A total of 3604 patients from ten trials were evaluated, with a median PSA value of 24 ng/ml. Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), cT3-4 disease (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with poorer outcomes. Adjusted 5-yr MFS rates were 83% and 78%, and 10-yr MFS rates were 63% and 53% for patients with one and two to three RFs, respectively; corresponding 10-yr adjusted OS rates were 67% and 60%, respectively. In cN1 patients, adjusted 5- and 10-yr MFS rates were 67% and 36%, respectively, and 10-yr OS was 47%.

Conclusions and clinical implications: HRLPC patients with two to three RFs (and cN0) or cN1 disease had the poorest outcomes on RT and ltADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC.

Patient summary: Radiotherapy and long-term hormone therapy are standard treatments for high-risk and locoregional prostate cancer. In this report, we defined prognostic groups within high-risk/locoregional prostate cancer and showed that outcomes to standard therapy are poorest in those with two or more "high-risk" factors or evidence of lymph node involvement. Such patients may therefore be the best candidates for intensification of treatment.

Background and objective: The 2024 US Food and Drug Administration approval of erdafitinib for the treatment of metastatic urothelial carcinoma (mUC) with FGFR3 alterations ushered in the era of targeted therapy for bladder cancer. In this review, we summarize the effects of FGFR pathway alterations in oncogenesis, clinical data supporting FGFR inhibitors in the management of bladder cancer, and the challenges that remain.

Methods: Original articles relevant to FGFR inhibitors in urothelial cancer between 1995 and 2024 were systematically identified in the PubMed and MEDLINE databases using the search terms "FGFR" and "bladder cancer". An international expert panel with extensive experience in FGFR inhibitor treatment was convened to synthesize a collaborative narrative review.

Key findings and limitations: Somatic FGFR3 alterations are found in up to 70% of low-grade non-muscle-invasive bladder cancers; these activate downstream signaling cascades and culminate in cellular proliferation. Beyond a link to lower-grade/lower-stage tumors, there is little consistency regarding whether these alterations confer prognostic risks for cancer recurrence or progression. FGFR3-altered tumors have been linked to a non-inflamed tumor microenvironment, but paradoxically do not seem to impact the response to systemic immunotherapy. Several pan-FGFR inhibitors have been investigated in mUC. With the introduction of novel intravesical drug delivery systems, FGFR inhibitors are poised to transform the therapeutic landscape for early-stage UC.

Conclusions and clinical implications: With deepening understanding of the biology of bladder cancer, novel diagnostics, and improved drug delivery methods, we posit that FGFR inhibition will lead the way in advancing precision treatment of bladder cancer.