European urology oncology最新文献

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: 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.