European urology oncology最新文献

Background: Salvage radiation therapy (SRT) is a mainstay of treatment for biochemical relapse following radical prostatectomy; however, few studies have examined genomic biomarkers in this context.

Objective: We characterized the prognostic impact of previously identified deleterious molecular phenotypes-loss of PTEN, ERG expression, and TP53 mutation-for patients undergoing SRT.

Design, setting, and participants: We leveraged an institutional database of 320 SRT patients with available tissue and follow-up. Tissue microarrays were used for genetically validated immunohistochemistry assays.

Intervention: All men underwent SRT with or without androgen deprivation therapy OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox-proportional hazard models assessed the association of molecular phenotypes with biochemical recurrence-free (bRFS) and metastasis-free (MFS) survival after SRT.

Results and limitations: Loss of PTEN (n = 123, 43%) and ERG expression (n = 118, 39%) were common in this cohort, while p53 overexpression (signifying TP53 missense mutation) was infrequent (n = 21, 7%). In univariable analyses, any loss of PTEN portended worse bRFS (hazard ratio [HR] 1.86; 95% confidence interval 1.36-2.57) and MFS (HR 1.89; 1.21-2.94), with homogeneous PTEN loss being associated with the highest risk of MFS (HR 2.47; 1.54-3.95). Similarly, p53 overexpression predicted worse bRFS (HR 1.95; 1.14-3.32) and MFS (HR 2.79; 1.50-5.19). ERG expression was associated with worse MFS only (HR 1.6; 1.03-2.48). On the multivariable analysis adjusting for known prognostic features, homogeneous PTEN loss remained predictive of adverse bRFS (HR 1.82; 1.12-2.96) and MFS (HR 2.08; 1.06-4.86). The study is limited by its retrospective and single-institution design.

Conclusions: PTEN loss by immunohistochemistry is an independent adverse prognostic factor for bRFS and MFS in prostate cancer patients treated with SRT. Future trials will determine the optimal approach to treating SRT patients with adverse molecular prognostic features.

Patient summary: Loss of the PTEN tumor suppressor protein is associated with worse outcomes after salvage radiotherapy, independent of other clinical or pathologic patient characteristics.

Background: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa).

Objective: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion.

Design, setting, and participants: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis.

Outcome measurements and statistical analysis: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2.

Results and limitations: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set.

Conclusions: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy.

Patient summary: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.

Background and objective: Prostate Imaging for Recurrence Reporting (PI-RR) was introduced in 2021 to standardize the interpretation and reporting of multiparametric magnetic resonance imaging (MRI) for prostate cancer following whole-gland treatment. The system scores image on a scale from 1 to 5 and has shown promising results in single-center studies. The aim of our systematic review and meta-analysis was to assess the diagnostic performance of the PI-RR system in predicting the likelihood of local recurrence after whole-gland treatment.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for diagnostic test accuracy were followed. Relevant databases were searched up to December 2023. Primary studies met the eligibility criteria if they reported MRI diagnostic performance in prostate cancer recurrence using PI-RR. Diagnostic performance for MRI was assessed using two different cutoff points (≥3 or ≥4 for positivity according to the PI-RR system). A meta-analysis with a random-effects model was used to estimate pooled sensitivity and specificity values.

Key findings and limitations: Sixteen articles were identified for full-text reading, of which six were considered eligible, involving a total of 467 patients. Using a cutoff of PI-RR ≥3 (4 studies) for recurrent disease, the sensitivity was 77.8% (95% confidence interval [CI] 69.9-84.1%) and the specificity was 80.2% (95% CI 58.2-92.2%). Using a cutoff of PI-RR ≥4 (4 studies), the sensitivity was 61.9% (95% CI 35.6-82.7%) and the specificity was 86.6% (95% CI 75.1-93.3%). Overall, the inter-rater agreement varied from fair to excellent.

Conclusions and clinical implications: PI-RR is accurate in detecting local recurrence after whole-gland treatment for prostate cancer and shows fair-to-good to excellent inter-reader agreement. Overall, a PI-RR cutoff of ≥3 showed high sensitivity and specificity.

Patient summary: We reviewed studies that reported on how good MRI scans using a scoring system called PI-RR were in detecting recurrence of prostate cancer. We found that this system shows good performance, with fair to excellent agreement between different radiologists.

The National Comprehensive Cancer Network (NCCN) very low risk (VLR) category for prostate cancer (PCa) represents clinically insignificant disease, and detection of VLR PCa contributes to overdiagnosis. Greater use of magnetic resonance imaging (MRI) and biomarkers before patient selection for prostate biopsy (PBx) reduces unnecessary biopsies and may reduce the diagnosis of clinically insignificant PCa. We tested a hypothesis that the proportion of VLR diagnoses has decreased with greater use of MRI-informed PBx using data from our 11-hospital system. From 2018 to 2023, 351/3197 (11%) men diagnosed with PCa met the NCCN VLR criteria. The proportion of VLR diagnoses did not change from 2018 to 2023 (p = 0.8) despite an increase in the use of MRI-informed PBx (from 49% to 82%; p < 0.001). Of patients who underwent combined systematic and targeted PBx and were diagnosed with VLR disease, cancer was found in systematic PBx regions in 79% of cases and in targeted PBx regions in 31% of cases. When performing both systematic and targeted PBx, prebiopsy MRI-based risk calculators could limit VLR diagnosis by 41% using a risk threshold of >5% for Gleason grade group ≥3 PCa to recommend biopsy; the reduction would be 77% if performing targeted PBx only. These findings suggest that VLR disease continues to account for a significant minority of PCa diagnoses and could be limited by targeted PBx and risk stratification calculators. PATIENT SUMMARY: We looked at recent trends for the diagnosis of very low-risk (VLR) prostate cancer. We found that VLR cancer still seems to be frequently diagnosed despite the use of MRI (magnetic resonance imaging) scans before biopsy. The use of risk calculators to identify men who could avoid biopsy and/or biopsy only for lesions that are visible on MRI could reduce the overdiagnosis of VLR prostate cancer.

Background and objective: A meta-analysis of two randomized STAMPEDE platform trials revealed that 3 yr of abiraterone acetate in addition to androgen deprivation therapy and radiation therapy significantly improved metastasis-free and overall survival (OS) in high-risk nonmetastatic prostate cancer (PCa) and should be considered a new standard of care. The aim of our study was to assess long-term cancer-specific survival (CSS) and OS for surgically treated patients with newly diagnosed nonmetastatic node-negative PCa meeting the STAMPEDE criteria for high risk.

Methods: This was a retrospective, multicenter cohort study of patients with European Association of Urology (EAU) high-risk PCa who underwent radical prostatectomy and extended pelvic lymph node dissection. CSS was assessed using cumulative incidence curves and the Kaplan-Meier method was used to evaluate OS. We used a Fine and Gray model to evaluate the prognostic value of STAMPEDE high-risk factors (SHRFs) for CSS, and a Cox proportional-hazards model to assess the association of SHRFs with OS.

Key findings and limitations: A total of 2994 patients with EAU high-risk PCa were divided into groups with 0, 1, 2, or 3 SHRFs. The 10-yr survival estimates for patients with 0-1 versus 2-3 SHRFs were 95% versus 82% for CSS and 81% versus 64% for OS (both p < 0.0001). In comparison to patients with 0 SHRFs, hazard ratios were 1.2 (p = 0.5), 3.9 (p < 0.0001), and 5.5 (p < 0.0001) for CSS, and 1.1 (p = 0.4), 2.2 (p < 0.0001), and 2.5 (p = 0.0004) for OS for patients with 1, 2, and 3 SHRFs, respectively.

Conclusions and clinical implications: Our results confirm that the STAMPEDE high-risk criteria identify a subgroup of patients with highly aggressive PCa features and adverse long-term oncological outcomes. This population is likely to benefit most from aggressive multimodal treatment. Nevertheless, we have shown for the first time that surgery remains a viable treatment option for patients with STAMPEDE high-risk PCa.

Patient summary: Prostate cancer that meets the high-risk definitions from the STAMPEDE trial is an aggressive type of cancer. Our results for long-term cancer control outcomes indicate that surgery is a viable option for the subgroup of patients with this type of prostate cancer.

Background: Although several studies have shown favorable outcomes in upper tract urothelial carcinoma (UTUC) with fibroblast growth factor receptor 3 (FGFR3) mutations and/or expression, the relationship between immune cell markers and FGFR3 expression remains unknown.

Objective: To clarify the FGFR3-based immune microenvironment and investigate biomarkers to predict the treatment response to pembrolizumab (Pem) in patients with UTUC.

Design, setting, and participants: We conducted immunohistochemical staining in 214 patients with UTUC. The expression levels of FGFR3, CD4, CD8, CD68, CD163, CD204, and programmed cell death ligand 1 (PD-L1) were examined.

Intervention: All UTUC patients underwent radical nephroureterectomy.

Outcome measurements and statistical analysis: We assessed the relationship between these immune markers and patient prognosis.

Results and limitations: A total of 109 (50.9%) patients showed high FGFR3 expressions and a favorable prognosis compared with the remaining patients. Among the six immune markers, CD8 high expression was an independent favorable factor, whereas CD204 expression was an independent prognostic factor for cancer death. From the FGFR3-based immune clustering, three immune clusters were identified. Cluster A showed low FGFR3 with tumor-associated macrophage-rich components (CD204⁺) followed by a poor prognosis due to a poor response to Pem. Cluster B showed low FGFR3 with an immune hot component (CD8⁺), followed by the most favorable prognosis owing to a good response to Pem. Cluster C showed high FGFR3 expression but an immune cold component, followed by a favorable prognosis due to the high FGFR3 expression, but a poor response was confirmed with Pem.

Conclusions: Although most patients exhibit a poor response to Pem, individuals with low FGFR3 expression and immune hot status may benefit clinically from Pem treatment.

Patient summary: We conducted immunohistochemical staining to evaluate fibroblast growth factor receptor 3 (FGFR3)-related immune microenvironment by evaluating the expressions of CD4, CD8, CD68, CD163, CD204, and PD-L1 in 214 upper tract urothelial carcinoma patients. We identified three distinct immune clusters based on FGFR3 expressions and found that patients with a low FGFR3 expression but immune hot status received the maximum benefit from an immune checkpoint inhibitor.