European urology oncology最新文献

For prostate cancer patients with metachronous nodal oligorecurrences detected by positron emission tomography, the randomized phase 2 PEACE V-STORM trial (NCT03569241) demonstrated that, compared with metastasis-directed therapy (MDT), elective nodal pelvic radiotherapy (ENRT) in combination with 6 mo of androgen deprivation therapy (ADT) improved locoregional disease control and metastasis-free survival. In the 190 evaluable patients (MDT: 97 and ENRT: 93) of the 196 randomized in the study, health-related quality of life (HRQoL) was assessed by European Organization for Research and Treatment of Cancer QLQ-C-30 and QLQ-PR-25 questionnaires over a 4-yr period as a part of a statistically defined quality of life analysis. During a median follow-up of 50 mo (interquartile range 42-58), QLQ-C30 scores showed no significant differences between MDT and ENRT, except for worse physical functioning at month 24 in the ENRT group (mean decline -7.7 vs -1.3) and worse emotional functioning at month 12 in the MDT group (mean decline 5.8 vs -0.4, p = 0.034). No significant differences in QLQ-PR25 scores were observed, except slightly better bowel symptoms at 18 mo for ENRT, but with no difference before or after. The decline in sexual activity and increase in ADT-related symptoms during the first 6 mo were comparable between arms, returning to baseline by month 12. Consistent with physician-reported treatment-related adverse events, HRQoL analyses show no significant differences between ENRT and MDT.

Background and objective: Real-world evidence on the effectiveness of first-line immuno-oncology (IO)-based combinations or cabozantinib (CABO) over traditional targeted therapies in metastatic non-clear cell renal cell carcinoma (nccRCC) is limited. This study aims to compare the outcomes of first-line therapies for metastatic nccRCC according to histologic subtypes, including papillary renal cell carcinoma (RCC), unclassified RCC, and chromophobe RCC with or without sarcomatoid dedifferentiation.

Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium, patients with metastatic nccRCC who received (1) IO plus vascular endothelial growth factor (IOVE) combination therapy, (2) IOIO doublet therapy, (3) CABO monotherapy, (4) sunitinib or pazopanib (SUN/PAZ) monotherapy, or (5) mammalian target of rapamycin (mTOR) monotherapy were included. Baseline patient characteristics, clinician assessment of objective response rates (ORRs), and overall survival (OS) were compared across first-line therapy regimens.

Key findings and limitations: The most common nccRCC histology was papillary found in 725 (47%), and sarcomatoid dedifferentiation was found in 236 (15%) of the 1551 patients included. Within the papillary RCC cohort, ORRs and median OS were, respectively, 31% and 33.2 mo for IOVE, 26% and 31.9 mo for IOIO, and 37% and 30.7 mo for CABO, as compared with 13% and 17.2 mo for SUN/PAZ and 3.4% and 13.1 mo for mTOR. Within the sarcomatoid dedifferentiation cohort, receipt of IOIO was associated with the highest ORR and the longest median OS (39.0% and 31.9 mo, respectively).

Conclusions and clinical implications: Distinct patient outcomes were observed across histologic subtypes. More histology-specific strategies are required given the differential activity of first-line therapy regimens against each nccRCC histology.

Background and objective: Partners of prostate cancer (PCa) patients may play an important role in the care process. Therefore, Europa Uomo initiated the Europa Uomo Prostate cancer Partners in Europe Research (EU-ProPER) study to study the partner's perspective. The study aims to assess the quality of life of partners of PCa patients, and the impact of a PCa diagnosis and its subsequent treatment on the partner.

Methods: Based on information of the PCa-partner program of the annual Dutch PCa Foundation meetings and expert input, a partner survey was developed. The survey includes themes on communication, relationship, social functioning, and general health (12-item Short Form Health Survey v2) of the partner, and the impact of urinary incontinence (UI) and sexual dysfunction (SD). The EU-ProPER survey was pretested in 16 partners and was available online in 17 languages.

Key findings and limitations: Between October 9 and Dec 31, 2023, 1135 partners completed the survey. The median age at completion was 68 yr (interquartile range [IQR] 62-73); it was 61 yr (IQR 55-67) at the time of diagnosis. Of the partners, 89% can openly talk about PCa to their partner and 73% feels that communication has not gotten worsen since the PCa diagnosis. Communication about UI and SD is more private. Regarding communication with health care professionals, PCa patients and partners are more often informed about UI (66%) than about intimacy/SD (20-24%). Most partners feel, however, that information about sexuality should be provided upfront to both the PCa patient and the partner (87%).

Conclusions and clinical implications: Europa Uomo has engaged an unprecedented number of partners of PCa patients. Communication is an important topic in which intimate topics such as UI and SD are more private. Communication with health care professionals about intimacy/sexuality is currently suboptimal and needs to be improved.

Background and objective: The surgical plan in robotic-assisted radical prostatectomy (RARP) aims to achieve optimal perioperative, oncological, and functional outcomes by recommending the extent of resection and use of function sparing techniques. However, there is a lack in high-level evidence on the optimal process to define the plan preoperatively. We therefore undertook a consensus exercise to develop the best practice statement to supplement evidence-based guidelines.

Methods: A consensus exercise was undertaken using a modified RAND/University of California Los Angeles approach. Consensus was a priori defined as ≥75% agreement/disagreement. A total of 101 statements were developed by the steering group based on a previously published systematic review and were reviewed in three rounds by 14 panellists.

Key findings and limitations: Overall, 73 statements reached consensus and 34 reached consensus across six domains. The process concluded that a preoperative surgical plan is essential prior to undertaking any RARP and will facilitate the optimal execution of surgery, as it provides the best available information to the surgeon to refine the technique and potentially improve oncological, functional, and perioperative outcomes.

Conclusions and clinical implications: The consensus statements draw out the best practices in the surgical planning process and can assist surgeons in standardising their approach. Gaps (areas of nonconsensus) have also been identified that can direct future work.

Background and objective: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown that prostate-specific antigen (PSA)-based screening reduces prostate cancer (PCa)-specific mortality (PCSM). However, the mediating role of a stage shift and curative treatment in the causal pathway from screening to reduced PCSM has not been elucidated.

Methods: In the ERSPC trial, men were randomly allocated to either a screening arm, with regular PSA measurements, or a control arm. During 16-yr follow-up, 8046 men from Finland, 3701 from the Netherlands, and 1382 from Sweden were diagnosed with PCa and were aged 55-69 yr at the time of randomization. A directed acyclic graph was used to define the impact of screening on the PCa-specific restricted mean survival time (RMST) after randomization, mediated by risk group and treatment at diagnosis.

Key findings and limitations: The absolute increase in RMST over 16 yr for men in the screening arm versus the control arm was 0.13 yr (95% confidence interval [CI] 0.05-0.22) in Finland, 0.48 yr (95% CI 0.24-0.62) in the Netherlands, and 0.44 yr (95% CI 0.22-0.68) in Sweden. This effect was mainly attributable to risk group at diagnosis, and not through treatment at the time of diagnosis. A limitation of the study is that we only included the three largest ERSPC centers.

Conclusions and clinical implication: The reduced PCSM achieved by early PCa detection via PSA-based screening is caused by more favorable prognostic features and subsequent improved treatment outcomes. Our findings confirm that the observed results are a causal effect of screening.

Background and objective: Management of oligometastatic renal cell carcinoma (omRCC) remains undefined, especially in favorable- and intermediate-risk patients, in whom treatment de-escalation may reduce toxicity and preserve quality of life. This study aims to evaluate sequential stereotactic ablative radiotherapy (SAbR) as first-line therapy in systemic therapy-naïve patients with omRCC.

Methods: A prospective, single-arm, phase 2b trial enrolled systemic therapy-naïve renal cell carcinoma (RCC) patients with three or fewer extracranial metastases, all treated with SAbR to all sites. The primary endpoint was to measure the percentage of patients with time to systemic therapy (TTST) >1 yr. Modified progression-free survival (mPFS) was defined as the earliest time of developing one of the following predefined criteria for local therapy escalation: more than three new metastases, more than six total metastases, local failure at an SAbR-treated site, brain metastases, or lesions not amenable to SAbR. The secondary endpoints included mPFS, progression-free survival on subsequent therapy, overall survival (OS), cancer-specific survival (CSS), local control, toxicity, and health-related quality of life (HRQoL).

Key findings and limitations: Twenty-three patients received SAbR to 69 lesions. The median follow-up was 45 mo. TTST >1 yr was achieved in 91% of patients; the median TTST was 55.6 mo. The median mPFS was 40 mo. Local control was 100%. The 3-yr OS and CSS rates were 68.7% and 87.0%, respectively. One patient developed grade 3 colitis possibly related to SAbR, progressing to grade 5 following immunotherapy. HRQoL remained stable. Single-arm design limits causal inference and generalizability.

Conclusions and clinical implications: Sequential SAbR achieved durable disease control and was not associated with significant changes in patient-reported quality of life, supporting a survivorship-centered, de-escalation strategy that avoids early systemic therapy in selected omRCC patients.

Background and objective: The role of ultrahypofractionated (UH) whole-pelvis radiotherapy (WPRT) as an alternative to conventionally fractionated (CF) WPRT is not well defined.

Methods: HOPE is a phase 2, multi-institutional, unblinded, randomized clinical trial designed to compare toxicity and patient-reported outcomes between UH-WPRT and CF-WPRT using the Expanded Prostate Cancer Index Composite (EPIC-50) questionnaire at 1 yr after treatment. Eighty patients with unfavorable intermediate-risk, high-risk, or very high-risk disease for whom high-dose-rate prostate brachytherapy was planned were randomly assigned 1:1 to either CF-WPRT or UH-WPRT.

Key findings and limitations: Baseline clinical characteristics were similar for the CF-WPRT (39 patients) and UH-WPRT (41 patients) arms. All patients received treatment according to their randomization allocation. Median follow-up was 3.34 yr. At 1 yr after radiotherapy, the mean (± standard deviation) EPIC bowel function score was noninferior between the CF-WPRT and UH-WPRT arms (88.4 ± 12.1 vs 90.6 ± 11.1; p = 0.0016 for noninferiority). Similarly, the mean EPIC bowel total score (86.7 ± 14.2 vs 89.0 ± 12.3; p = 0.24) and bother score (85.0 ± 18.0 vs 87.4 ± 16.3; p = 0.28) did not significantly differ between the arms. No significant differences in EPIC urinary subdomains at 1 yr were observed between the arms. No late (>6 wk) grade 3-5 genitourinary or gastrointestinal toxicities were reported in the CF-WPRT arm, while one patient in the UH-WPRT arm experienced grade 3 genitourinary toxicity. The data are not yet mature enough for evaluation of oncological endpoints.

Conclusions and clinical implications: Results from the HOPE trial demonstrate that UH-WPRT is as well tolerated as CF-WPRT when combined with a high-dose-rate brachytherapy boost to the prostate.