European urology oncology最新文献

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated. PATIENT SUMMARY: We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies.

Background and objective: Survivors of testicular germ cell tumor (TGCT) may experience long-term cognitive changes. The aim of our prospective study was to longitudinally assess cognitive function among TGCT survivors to identify potential lasting cognitive changes over a period of 5 yr.

Methods: TGCT survivors (n = 151) completed Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaires annually, with median time to first follow-up visit (FUV) of 8 (range 4-24) yr since completion of treatment. Treatment after orchiectomy included: active surveillance (AS) alone (n = 21); chemotherapy (CTx; n = 109); radiotherapy (RT) to the retroperitoneum (n = 11); and combined CTx + RT (n = 10). Scores for four FACT-Cog domains and overall cognitive scores were evaluated annually for 5 yr. In a subgroup analysis we compared results for survivors who received cisplatin at a dose of <400 mg/m² (n = 48) versus ≥400 mg/m² (n = 70).

Results: The CTx + RT group had persistently lower scores for the perceived cognitive abilities (CogPCA) domain annually between the first and fifth FUVs in comparison to the AS group (all p < 0.05), with lower overall cognitive scores from the second to the fifth FUV (all p < 0.03). The group that received ≥400 mg/m² cisplatin had lower CogPCA scores at the first and second FUVs, and lower overall cognitive scores at the second FUV in comparison to the AS group. However, no significant change in cognitive scores across all domains was observed over 5 yr for all survivors.

Conclusions: Cognitive impairment in TGCT survivors persisted over long-term follow-up. Survivors who received both CTx and RT consistently had the worst cognitive performance at all FUVs over a 5-yr period. In addition, survivors who received a higher cisplatin dose showed worse cognitive function at all FUVs.

Patient summary: Our study results show that survivors of testicular cancer experienced long-term cognitive dysfunction that persisted over time. Survivors who underwent both chemotherapy and radiotherapy and those who received a higher dose of chemotherapy had the worst cognitive problems.

Background and objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is increasingly used for primary staging in prostate cancer. Owing to accurate detection of small metastases on PSMA-PET/CT, patient selection for robot-assisted radical prostatectomy (RARP) has likely changed. This study analyzes oncological outcomes in patients undergoing RARP and extended pelvic lymph node dissection (ePLND) after PSMA-PET/CT staging, compared with those without PSMA-PET/CT.

Methods: Patients who underwent staging with PSMA-PET/CT before RARP and ePLND ("PSMA cohort"; 2016-2021) were compared with patients staged without PSMA-PET/CT ("historical cohort"; 2013-2016). Propensity score matching using preoperative variables was performed to limit confounding. As primary outcome measure of biochemical recurrence (BCR)-free survival (BFS) was analyzed, with BCR defined as a prostate specific antigen value of ≥0.2 ng/ml or start of additional therapy after surgery.

Key findings and limitations: After matching, 880 patients were included (440 in each cohort). The median follow-up was 35 mo (interquartile range 21-60) for the entire cohort. In the PSMA cohort, 126/440 patients (29%) experienced BCR versus 205/440 (47%) in the historical cohort (log-rank test p = 0.032). A multivariable Cox regression analysis showed an independent effect of preoperative PSMA-PET/CT staging on BFS (hazard ratio 0.70, 95% confidence interval 0.55-0.89, p = 0.0030).

Conclusions and clinical implications: Patients who underwent staging with PSMA-PET/CT had longer biochemical progression-free survival after RARP and ePLND than those without PSMA-PET/CT. This suggests that PSMA-PET/CT staging alters patient selection for RARP and ePLND, and is associated with improved early oncological outcomes for patients who still undergo surgery.

Patient summary: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) at the diagnosis of prostate cancer leads to better visualization of metastases and therefore better selection of prostate cancer patients for surgery. Patients who underwent a PSMA-PET/CT scan at the time of diagnosis showed improved oncological outcomes, including longer progression-free survival and less prostate-specific antigen persistence after surgery.

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.

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.