European urology oncology最新文献

Background and objective: Non-muscle-invasive bladder cancer (NMIBC) patients treated with additional bacillus Calmette-Guérin (BCG) may become unresponsive to BCG. Recently, sequential intravesical gemcitabine and docetaxel (gem/doce) are being used for NMIBC. This study aims to compare oncologic outcomes between sequential intravesical gem/doce versus additional BCG in patients with BCG-unresponsive NMIBC.

Methods: Data were collected from ten academic institutions on patients with BCG-unresponsive NMIBC based on the Food and Drug Administration guidelines. Information on high-grade recurrence-free (HGRFS), progression-free (PFS), cystectomy-free (CFS), metastasis-free (MFS), cancer-specific (CSS), and overall (OS) survival was collected. The Kaplan-Meier method and Cox proportional hazard ratios (HRs) were used to determine differences in oncologic outcomes between the Gem/Doce and BCG groups.

Key findings and limitations: Of 299 total patients, 204 underwent additional BCG treatment at the time of BCG unresponsiveness and 95 underwent gem/doce treatment. Rates of PFS (HR 2.6, 95% confidence interval [CI] 1.1-5.0, p = 0.03), CFS (HR 2.0, 95% CI 1.2-3.4, p = 0.01), and CSS (HR 3.7, 95% CI 1.1-12.3, p=0.03) were higher in patients receiving gem/doce. HGRFS, MFS, and OS were similar between both groups.

Conclusions and clinical implications: The findings from this study suggest that intravesical gem/doce is associated with lower rates of progression than additional BCG in patients with BCG-unresponsive NMIBC who decline or are ineligible for cystectomy.

Patient summary: In this report, we looked at outcomes between patients with noninvasive bladder cancer who were treated with additional bacillus Calmette-Guérin (BCG) or gemcitabine-docetaxel combination after not responding to primary BCG therapy. We found that intravesical gemcitabine-docetaxel was associated with fewer progression events than additional salvage BCG therapy.

Background and objective: There is a lack of data on the impact of hypoglycemia agents, especially metformin, on prognosis for non-muscle-invasive bladder cancer (NMIBC). Our aim was to investigate the association between hypoglycemia agents, especially metformin, and long-term survival outcomes for patients with NMIBC treated with bacillus Calmette-Guérin.

Methods: All patients with NMIBC treated with intravesical BCG therapy from 2001 to 2020 were identified in a territory-wide database in Hong Kong. Patients were stratified into two groups according to whether or not they were taking a hypoglycemia agent at BCG treatment initiation. We analyzed data for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust for potential confounding factors and estimate hazard ratio (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to assess the specific influence of metformin on survival outcomes.

Key findings and limitations: Of 2602 patients with NMIBC treated with intravesical BCG, 19.5% (n = 507) were taking a hypoglycemia agent at BCG initiation (treatment group) and 80.5% (n = 2095) were not (control group). At median follow-up of 11 yr, Kaplan-Meier analysis revealed a significant difference in OS between the groups (p < 0.01), but not in CSS (p = 0.36), RFS (p = 0.19), or PFS (p = 0.05). Subgroup analysis comparing outcomes for patients taking metformin, patients taking a hypoglycemia agent other than metformin, and control subjects revealed significant differences in OS (p < 0.01) and RFS (p = 0.02), but not in CSS (p = 0.59) or PFS (p = 0.08). Multivariable Cox regression analysis identified metformin-based treatment for hypoglycemia as an independent risk factor for RFS (HR 1.22, 95% CI 1.02-1.46), whereas hypoglycemia agents other than metformin were not significantly associated with RFS (HR 0.71, 95% CI 0.47-1.06).

Conclusions and clinical implications: Metformin-based hypoglycemia treatment was an independent risk factor for RFS in BCG-treated NMIBC. Hypoglycemia treatment with an agent other than metformin was not related to long-term survival outcomes.

Patient summary: We investigated the relationship between treatment for high blood sugar and long-term survival for patients with intermediate-risk or high-risk non-muscle-invasive bladder cancer. The patients had received BCG (bacillus Calmette-Guérin) treatment in Hong Kong for their bladder cancer over the past two decades. Our results show that metformin, but not other drugs used to treat high blood sugar, was associated with poorer survival free from bladder cancer recurrence for these patients.

Targeted microwave ablation (TMA) is a novel focal therapy modality for prostate cancer (PC). TMA-HK is the first phase 2 trial investigating the efficacy and functional outcomes of transperineal TMA (NCT04113811) in 30 men with low- or intermediate-risk PC. TMA was performed transperineally with magnetic resonance imaging (MRI)-ultrasound fusion guidance and organ-based tracking. All participants underwent prostate MRI at 6 mo after TMA, followed by targeted and 18-core systematic prostate biopsy. The primary outcome was cancer detection on biopsy in each ablated area at 6 mo. Secondary outcomes included per-patient analysis of positive biopsy results, complications, and functional outcomes at 12 mo. A total of 42 areas were treated in 30 patients (seven low-risk and 23 intermediate-risk PC), with no cancer detected in 90.5% (38/42) of the treated areas. Per-patient analysis revealed in-field recurrence in 10.0% (three of 30) of patients, of whom two had grade group 1 and one had grade group 2 disease. At 12 mo, out-of-field biopsies were positive in 40.0% (12/30) of the patients (ten grade group 1, two grade group 2 disease). Only self-limiting grade 1 and 2 complications were reported. Three patients (10.0%) reported de novo failure to achieve penetrative sexual intercourse. The results demonstrate that TMA for PC resulted in effective ablation, with good cancer control up to 12 mo. PATIENT SUMMARY: We performed the first efficacy trial of targeted microwave treatment for prostate cancer in 30 patients with low- or intermediate-risk disease. Our results show that this treatment achieved excellent local control of the cancer up to 12 months, with a low rate of complications. More research in larger patient groups and over longer follow-up is needed to confirm these findings.

Background and objective: Owing to the expansion of treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) and an appreciation of clinical subgroups with differential prognosis and treatment responses, prognostic and predictive biomarkers are needed to personalize care in this setting. Our aim was to evaluate a multimodal artificial intelligence (MMAI) biomarker for prognostic ability in mHSPC.

Methods: We used data from the phase 3 CHAARTED trial; 456/790 patients with mHSPC had evaluable digital histopathology images and requisite clinical variables to generate MMAI scores for inclusion in our analysis. We assessed the association of MMAI score with overall survival (OS), clinical progression (CP), and castration-resistant PC (CRPC) via univariable Cox proportional-hazards and Fine-Gray models.

Key findings and limitations: In the analysis cohort, 370 patients (81.1%) were classified as MMAI-high and 86 (18.9%) as MMAI-intermediate/low risk. Estimated 5-yr OS was 39% for the MMAI-high, 58% for the MMAI-intermediate, and 83% for the MMAI-low groups (log-rank p < 0.001). The MMAI score was associated with OS (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.33-1.73; p < 0.001), CP (subdistribution HR 1.54, 95% CI 1.36-1.74; p < 0.001), and CRPC (subdistribution HR 1.63, 95% CI 1.45-1.83; p < 0.001). The proportion of MMAI-high cases was 50.0%, 83.7%, 66.7%, and 92.1% in the subgroups with low-volume metachronous (n = 74), low-volume synchronous (n = 80), high-volume metachronous (n = 48), and high-volume synchronous (n = 254) mHSPC, respectively. The MMAI biomarker remained prognostic after adjustment for treatment, volume status, and diagnosis stage.

Conclusions and clinical implications: Our findings show that the MMAI biomarker is prognostic for OS, CP, and CRPC among patients with mHSPC, regardless of clinical subgroup or treatment received. Further investigations of MMAI biomarkers in advanced PC are warranted.

Patient summary: We looked at the performance of an artificial intelligence (AI) tool that interprets images of samples of prostate cancer tissue in a group of men whose cancer had spread beyond the prostate. The AI tool was able to identify patients at higher risk of worse outcomes. These results show the potential benefit of AI tools in helping patients and their health care team in making treatment decisions.

Background and objective: Current guidelines on radiological follow-up (FU) for patients after treatment for nonmetastatic renal cell carcinoma (RCC) are not based on robust evidence. This review aims to evaluate whether the 2022 European Association of Urology (EAU) guidelines are noninferior, in terms of recurrence and (overall) survival, to a higher imaging frequency of computed tomography (CT) of the chest and abdomen.

Methods: A literature search of relevant search machines (PubMed/Medline and EMBASE) was performed up to May 29, 2024. Studies describing patients with nonmetastatic RCC who underwent curative treatment by means of partial or radical nephrectomy were included. Studies with a higher number of CT scans than recommended by the EAU were compared with those that followed guidelines by examining recurrences and survival data. Outcomes were classified into risk groups according to the 2022 EAU guidelines.

Key findings and limitations: Twenty studies met our inclusion criteria. Sixteen (80%) studies employed a higher imaging frequency during FU compared with 2022 EAU guideline recommendations, two studies (10%) followed the guidelines, and two studies (10%) performed less imaging. Recurrences were rare in low-risk studies (0-7.6%) and varied among high-risk studies, ranging between 33% and 40% in randomized controlled trials and 11% and 28% in retrospective studies. A meta-analysis was not suited due to clinical diversity, and the risk of bias was high among cohort studies.

Conclusions and clinical implications: Most studies employ a higher imaging frequency during FU after treatment for nonmetastatic RCC than recommended by the 2022 EAU guidelines. Survival and recurrence rates suggest that more frequent imaging than recommended by the EAU may not be advantageous, although high-quality evidence is needed to further improve guidelines.

Patient summary: In this review, we assessed radiological follow-up schedules for patients after surgery for kidney cancer and compared these with the follow-up schedules recommended by the European Association of Urology guidelines. We found that most studies apply more frequent imaging during follow-up than recommended by guidelines, although survival and recurrence rates are similar among studies with different imaging frequencies. We conclude that more frequent imaging than recommended by guidelines may not be necessary and that prospective studies are needed to determine whether imaging can be reduced further during follow-up.

Background and objective: Despite the evidence for prostate-specific antigen (PSA) screening reducing prostate cancer (PCa) mortality, the optimal PSA cutoff and the clinical significance of low initial PSA levels in predicting long-term PCa mortality remain subjects of ongoing research. We assessed PCa mortality among men with initial PSA levels below 3 ng/ml during the first screening round of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).

Methods: A retrospective cohort study was conducted, including 20 268 men from the screening arm of the FinRSPC with an initial PSA level of <3 ng/ml, with follow-up spanning up to 20 yr. Hazard ratios (HRs) and their 95% corresponding confidence intervals (CIs) were estimated using a Cox regression analysis.

Key findings and limitations: During a median follow-up of 17.8 yr, 1840 PCa cases were diagnosed and 128 PCa deaths occurred, with the cumulative PCa mortality of 0.6% and a mortality rate of four per 10 000 person-years. PCa mortality was five-fold higher at PSA levels of 2-2.99 ng/ml (HR 5.0, 95% CI 3.1-8.1) than at <1 ng/ml. Deaths from cases with Gleason score <7 and European Association of Urology low-risk group tumors showed a stronger association with PSA, particularly in the 2-2.99 ng/ml range versus <1 ng/ml. Additionally, PCa mortality in younger men (55-58 yr at entry) exhibited a stronger association with PSA than that in older men (67-71 yr at baseline). Addition of the cumulative number of PSA tests slightly improved the overall prediction of PCa death based on Harrell's C-statistic (base model 0.683 vs 0.717). The relatively small number of deaths, particularly among men with low-risk disease, may potentially limit the statistical precision of the results.

Conclusions and clinical implications: Our findings highlight the importance of a nuanced approach to PSA in PCa screening, suggesting utility for combining PSA with other tests at low levels and indicating minimal risk associated with discontinuing screening at ages 67-71 yr when PSA is low.

Patient summary: In this study, we analyzed prostate cancer deaths in Finnish men with low initial prostate-specific antigen (PSA) levels. We found that the risk of prostate cancer death increases in relation to PSA, especially in younger men. Screening might safely be stopped at ages 67-71 yr if PSA remains low.

Background and objective: Advanced prostate cancer (PCa) is enriched for alterations in DNA damage repair genes; poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a class of drugs that have demonstrated effectiveness in PCa, particularly in tumors with alterations in BRCA1/2 and other homologous recombination repair (HRR) genes, acting through a synthetic lethal mechanism. To prevent or delay drug resistance, and to expand the patient population that can benefit from this class of drug, combination treatment strategies have been developed in preclinical and clinical studies.

Methods: This review examines the latest developments in clinical trials testing PARPi for advanced PCa and their emerging role in earlier disease settings. Furthermore, it discusses the critical role of careful patient selection and identification of additional biomarkers to enhance treatment efficacy.

Key findings and limitations: Two PARPi (olaparib and rucaparib) have been approved as monotherapy in metastatic castration-resistant PCa, thereby establishing the first biomarker-guided drug indications in PCa. Several combinations of PARPi with androgen receptor pathway inhibitors have now also been approved. Anemia and fatigue are the main adverse events associated with this drug class in clinical trials; gastrointestinal toxicities are common but usually manageble.

Conclusions and clinical implications: PARPi are active against PCa with HRR mutations, especially in those with germline or somatic BRCA1/2 mutations.  There is still a need to further optimize patient stratification strategies, particularly for combination approaches. Future research should focus on refining predictive biomarkers, improving treatment delivery strategies, and exploring the potential benefits of PARPi in earlier stages of the disease.

Patient summary: Here, we summarize the results from clinical trials testing different poly (ADP-ribose) polymerase inhibitors (PARPi), a novel targeted drug class, in prostate cancer. Overall, the data from these trials confirm the efficacy of this drug class in those metastatic prostate cancers that show specific gene alterations, such as mutations in the BRCA1/2 genes. Several studies combining PARPi with other standard drugs for prostate cancer suggest that there may be efficacy in larger patient populations, but some of these data still need validation in longer follow-up analyses.

Background and objective: Circulating tumor DNA (ctDNA) testing provides valuable prognostic and predictive information for guiding therapeutic choices and monitoring disease progression and drug resistance for urological tumors. Our review focuses on emerging opportunities for ctDNA analysis in urological tumors and the development of potential circulating biomarkers within a multidisciplinary framework to improve personalized treatment.

Methods: A nonsystematic literature review was conducted in the PubMed and MEDLINE databases. Prospective and retrospective peer-reviewed studies, review articles, and research abstracts on the use of ctDNA for urological tumors were included.

Key findings and limitations: Several studies have demonstrated that ctDNA analysis is a promising tool that can help clinicians in the diagnosis and clinical management of urological tumors. In prostate and urothelial cancers, the ctDNA fraction increases proportionally from localized to metastatic disease, indicating a higher tumor burden and more aggressive behavior. Thus, ctDNA seems to be a useful tool for improving prognostic risk stratification and treatment selection. Data on the use of liquid biopsy in renal cell carcinoma are still limited, and assessment of prognostic and predictive biomarkers is a critical unmet need.

Conclusions and clinical implications: ctDNA analysis promises to revolutionize the management of urological tumors in different disease settings. Integration of ctDNA testing in routine clinical practice will require a multidisciplinary approach that involve patients, clinicians, and molecular biologists.

Patient summary: We reviewed how testing for tumor DNA in blood (circulating tumor DNA, ctDNA) is used in urological cancers. A great deal of evidence supports the usefulness of this noninvasive test. However, further research via a multidisciplinary approach is needed before ctDNA testing becomes part of routine patient care.