European urology oncology最新文献

Background and objective: Different substaging methods have been proposed for risk stratification of T1 non-muscle-invasive bladder cancer; however, no consensus exists. This systematic review and meta-analysis evaluates the prognostic value of various T1 substaging systems.

Methods: A systematic literature search was conducted using the PubMed/Medline, Embase, Scopus, and Web of Science databases to identify reports published until January 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The primary outcomes were disease recurrence and progression. A subgroup analysis evaluated histoanatomical and micrometric substaging within the same population.

Key findings and limitations: Fifty-seven studies met the inclusion criteria. Muscularis mucosae invasion was associated with progression (hazard ratio [HR]: 2.65, 95% confidence interval [CI]: 1.79-3.92, p < 0.001) but not with recurrence (HR: 1.19, 95% CI: 0.88-1.61, p = 0.3). Micrometric substaging (T1m/T1e, 0.5 mm cutoff) correlated with both recurrence (HR: 2.01, 95% CI: 1.53-2.64, p < 0.001) and progression (HR: 3.33, 95% CI: 2.47-4.49, p < 0.001). Considering the substaging systems applied to the same population, the pooled risk ratio (RR) for T1a versus T1b/c was 0.60 (95% CI: 0.45-0.80, p < 0.001), while the RR for T1m versus T1e was 0.39 (95% CI: 0.29-0.52, p < 0.001). The main limitation was heterogeneity in postsurgery management.

Conclusions and clinical implications: Histoanatomical substaging significantly associate with progression but not with recurrence. Micrometric substaging demonstrated an association with both recurrence and progression, potentially enhancing patient stratification. Rete Oncologica Lombarda substaging shows some promising results in stratifying patients. These results may support a global pathological consensus on the optimal T1 substaging system.

Background and objective: Radical nephroureterectomy is the standard of care for management of upper tract urothelial carcinoma (UTUC), but treatment-associated morbidity is not uncommon. Intracavitary therapy has emerged as a less invasive alternative for selected cases, particularly carcinoma in situ (CIS) and low-grade papillary tumors. We conducted a systematic review to evaluate the outcomes, recurrence rates, and adverse events associated with intracavitary therapy (immunotherapy or chemoablation) for UTUC.

Methods: The review protocol was registered on PROSPERO and adhered to PRISMA guidelines. The MEDLINE, Embase, and Cochrane databases were searched in October 2024 using terms related to UTUC and intraluminal therapy. Both randomized and nonrandomized studies and single-arm studies were included.

Key findings and limitations: We included 11 articles reporting on nine unique studies (368 patients in total) in the review. Four studies were in upper tract CIS and five were in papillary UTUC. For CIS, Bacillus Calmette-Guérin immunotherapy resulted in a CR rate ranging from 72.7% to 100%, and a 12-mo persistent response rate of 63.6-80%. For gemcitabine-docetaxel instillation in upper-tract CIS, the recurrence-free survival rate at 12 mo was 78%. For papillary UTUC, chemoablation with mitomycin gel (UGN-101) achieved CR rates of 36.4-57.7%, with 12-mo recurrence-free survival rates ranging from 13.6% to 53.1%. Adverse events included ureteric stricture (4.5-10%), hematuria (3.1-32.8%), and loin pain (18.8-34.4%).

Conclusions and clinical implications: Intracavitary therapy for UTUC in the form of BCG for CIS and mitomycin C for papillary disease shows considerable efficacy, with acceptable safety profiles. These therapies represent a renal-preserving alternative for patients unfit for surgery or at high risk of renal failure, and the evidence supports their use in carefully selected patients.

Background and objective: While gender disparities in bladder cancer are well documented in sexual and functional health domains, mental and social well-being among survivors are not elucidated fully. We aimed to investigate gender differences in mental well-being, social connectedness, and perceptions of respect among bladder cancer survivors.

Methods: We conducted a cross-sectional analysis from the All of Us Research Program of the National Institutes of Health, a nationwide cohort integrating survey responses and electronic health records (EHRs). Individuals with a diagnosis of malignant neoplasm of the bladder were included. The primary outcomes were self-reported overall mental and social health and EHR-documented depressive disorder. Multivariable logistic regression was adjusted for age, race, education/marital status, time since diagnosis, and comorbidities.

Key findings and limitations: Among 1085 individuals diagnosed with bladder cancer (319 women and 766 men), women had significantly higher odds of EHR-documented depressive disorder than men (adjusted odds ratio [interquartile range]: 2.86 [1.59, 3.82]; p < 0.001). A higher proportion of women reported lacking companionship (p = 0.007), feeling isolated (p = 0.025), experiencing stress (p < 0.001), and inability to cope (p < 0.001). Female scores for general mental and social health were decreased but were not significantly different after adjusting for covariates. No gender differences were observed in perceived respect/courtesy from health care providers.

Conclusions and clinical implications: Women with bladder cancer experience disproportionate psychosocial burden compared with men, particularly related to depression and social isolation. Certain disparities were not apparent after adjustment for socioeconomic factors and comorbidities, underscoring the need to support patients with predisposing factors to adverse mental outcomes. Routine psychosocial screening should be integrated into bladder cancer survivorship to identify and support vulnerable individuals.

Background and objective: While magnetic resonance imaging (MRI)-guided targeted biopsy (TBx) is becoming an integral part of early detection of prostate cancer (PC), its role in screening of younger men remains unclear. We analyzed the additional value of systematic biopsy (SBx) in improving detection of clinically significant PC (csPC).

Methods: A total of 525 men aged 45-54 yr with confirmed prostate-specific antigen ≥3.0 ng/ml underwent multiparametric MRI followed by combined TBx and SBx between February 2014 and August 2023 within a multicenter prospective screening trial in Germany. Software-based MRI/ultrasound fusion TBx (2 cores per lesion) combined with SBx was performed via a transrectal or transperineal approach. The primary objective was to analyze differences in csPC detection rates between SBx and TBx in relation to MRI. Secondary objectives were detection rates by International Society of Urological Pathology grade group (GG) and the distribution of SBx and/or TBx findings.

Key findings and limitations: PC was detected in 209 men (39%), of which 148/209 cases were csPC (71%; GG ≥2). SBx missed 24/148 csPC cases (16%) and TBx missed 49/148 (33%). SBx detected 25 more low-risk PC cases than TBx (51 vs 26). For 64% of the cases in which SBx detected higher GG than TBx (n = 89, including GG 1), the positive cores were located within MRI-detected lesions. Five GG ≥3 PC cases were not identified on MRI. Limitations include the lack of centralized MRI review before biopsy, variability in biopsy technique, retrospective subgroup analysis, and short follow-up.

Conclusions and clinical implications: A relevant proportion of csPC cases were missed by two-core TBx, although they were correctly identified on MRI, suggesting limitations in targeting accuracy and/or the fusion technique. SBx cores or targeted perilesional sampling, particularly in young men with smaller prostate volume, might be a valuable complement to TBx to ensure reliable and early detection of (cs)PC in this age group.

Patient summary: We looked at the effectiveness of systematic biopsy (usually 12 cores taken from the prostate gland) and targeted biopsy (cores from a suspicious area seen on a scan) of the prostate among men aged 45-54 years as part of a prostate cancer screening trial. The results show that using only two targeted cores per lesion seen on an MRI (magnetic resonance imaging) scan may miss a significant number of clinically relevant prostate cancers. One reason could be that MRI-targeted biopsies are not always perfectly accurate. To improve diagnostic accuracy in younger men, it may be necessary to take additional systematic tissue samples, or at least more samples from around any suspicious area. This trial is registered on ISRCTN as ISRCTN37591328.

Background and introduction: Over the past 15 yr, significant progress has been made in the management of prostate cancer (PC), including the development of chemotherapy, androgen receptor pathway inhibitors (ARPIs), and, more recently, radium-223 radioligand therapy. However, metastatic PC is still the third leading cancer-related cause of death among men in Europe, with a 5-yr survival rate of ∼30% and median overall survival (OS) of <3 yr for castration-resistant PC (CRPC). Current strategies are moving towards personalised treatment, with the emergence of PARP inhibitors (PARPi) that exploit a vulnerability in the DNA repair system in patients with alterations in genes involved in homologous recombination.

Methods: We reviewed the literature on PARPi treatment for CRPC and provide a narrative synthesis of the evidence for the rapidly evolving treatment landscape in this setting.

Key findings and limitations: Phase 3 studies evaluating the efficacy of PARPi agents available (olaparib, niraparib, rucaparib, and talazoparib) for the treatment of metastatic CRPC have confirmed their ability to prolong OS, especially in patients carrying BRCA1/2 mutations. Studies on PARPi + ARPI combinations have shown longer radiological progression-free survival, and better OS with talazoparib + enzalutamide, regardless of mutational status for DNA repair genes, with synergistic activity identified. However, response to PARPi seems to vary depending on the genes altered, with a greater benefit for patients with mutations in genes encoding the repair effector proteins BRCA1/2, CDK12, and PALB2.

Conclusions and clinical implications: Promising results have led to the approval of several PARPi agents as monotherapy or in combination with ARPIs in selected or unselected patients when chemotherapy is not clinically indicated. However, some questions remain regarding patient selection and treatment sequencing.

Background and objective: It is thought that androgen deprivation therapy (ADT) resistance and subsequent prostate cancer progression via epithelial-mesenchymal transition (EMT) is induced by the SRC and MEK pathways. We hypothesized that inhibition of these pathways could reduce EMT.

Methods: In this phase 2 trial, 45 patients undergoing prostatectomy for International Society of Urological Pathology grade group ≥3, prostate-specific antigen >20 ng/ml, and/or stage ≥cT3a localized prostate adenocarcinoma were randomized 1:1:1 to receive 6-8 wk of neoadjuvant ADT (enzalutamide + degarelix) alone or in combination with either an SRC inhibitor (dasatinib) or MEK inhibitor (trametinib). The primary endpoint was the abundance of EMT markers (N-cadherin and vimentin) on immunohistochemistry (IHC) after prostatectomy. Secondary outcomes included clinicopathologic outcomes, changes in EMT markers between biopsy and prostatectomy according to IHC and RNA abundance, and safety.

Key findings and limitations: IHC results for N-cadherin and vimentin after treatment did not differ by arm. No differences were observed in time to biochemical recurrence, time to testosterone recovery, or pathologic minimal residual disease. MAP2K1, MAP2K2, and SRC RNA abundance decreased significantly in all three arms. No patients experienced a grade ≥3 treatment-related adverse event.

Conclusions and clinical implications: Neoadjuvant SRC or MEK inhibition does not appear to mitigate the EMT response to ADT or influence clinical or pathological outcomes.

Background and objective: PROpel (NCT03732820) demonstrated a statistically significant radiographic progression-free survival (rPFS) benefit with olaparib plus abiraterone (Ola + Abi) versus placebo plus abiraterone (P + Abi) in first-line metastatic castration-resistant prostate cancer (mCRPC). We conducted exploratory analyses in the intention-to-treat (ITT) population and subgroups stratified by homologous recombination repair gene mutation (HRRm) and BRCA1 and/or BRCA2 mutation (BRCAm) status.

Methods: In PROpel, patients with mCRPC, without selection by HRRm status, were randomised 1:1 to first-line treatment with Ola (300 mg twice daily; n = 399) or P (n = 397), each with Abi (1000 mg daily) and prednisone/prednisolone (5 mg twice daily). The primary endpoint was investigator-assessed rPFS. Exploratory endpoints were the objective response rate (ORR), duration of response (DoR), confirmed ≥50 decrease in prostate-specific antigen (PSA₅₀-RR), and time to PSA progression; post hoc subgroup analyses by HRRm and BRCAm status were conducted.

Key findings and limitations: In the ITT population, the ORR was 58.4% with Ola + Abi versus 48.1% with P + Abi. The confirmed PSA₅₀-RR was 79.3% with Ola + Abi and 69.2% with P + Abi. Median time to PSA progression in the ITT population was 24.2 mo with Ola + Abi and 12.0 mo with P + Abi (HR 0.59; 95% CI, 0.49-0.71). In the HRRm, no-HRRm, BRCAm, and no-BRCAm subgroups, results for ORR, DoR, confirmed PSA₅₀-RR, and time to PSA progression favoured Ola + Abi, but these analyses were not powered for statistical significance.

Conclusions and clinical implications: Results for ORR, DoR, confirmed PSA₅₀-RR, and time to PSA progression favoured Ola + Abi over P + Abi in the ITT population and biomarker subgroups. The data support consideration of Ola + Abi as first-line treatment for mCRPC.

Background and objective: Prostate cancer is typically a disease of older men. As patients age, they develop comorbidities and require more medications, which may adversely affect or be affected by prostate cancer treatments. We investigated whether the survival benefits and favorable safety profile of darolutamide in the phase 3 ARASENS trial could be seen regardless of age.

Methods: Patients received darolutamide 600 mg or placebo orally twice daily plus androgen-deprivation therapy and docetaxel. Outcomes were assessed in subgroups of patients aged <75 yr (n = 1086) and ≥75 yr (n = 219).

Key findings and limitations: Most patients in both age groups had comorbidities (<75 yr: 94%; ≥75 yr: 97%) and concomitant medications (median 8-9). In both age subgroups, compared with placebo, darolutamide increased overall survival (<75 yr: hazard ratio 0.70 [95% confidence interval 0.58-0.84]; ≥75 yr: 0.61 [0.41-0.91]), delayed time to metastatic castration-resistant prostate cancer (<75 yr: 0.35 [0.30-0.43]; ≥75 yr: 0.42 [0.28-0.64]), and delayed time to initiation of subsequent therapy (<75 yr: 0.40 [0.34-0.48]; ≥75 yr: 0.35 [0.22-0.54]). Treatment-emergent adverse events were similar in the darolutamide/placebo groups, with slightly higher incidences in older patients. This analysis is limited by its post hoc nature.

Conclusions and clinical implications: In the 219 patients aged ≥75 yr in ARASENS, darolutamide demonstrated improved efficacy versus placebo and favorable safety, consistent with the findings in patients aged <75 yr. Thus, darolutamide and androgen-deprivation therapy with docetaxel can be considered a standard of care triplet therapy for metastatic hormone-sensitive prostate cancer regardless of patients' age.

Background and objective: The Targeted Prostate Health Check (TPHC) programme was set up to identify men with prostate cancer (PC) in the Surrey and Sussex region of England that was undetected during the COVID-19 era. We report outcomes for more than 18 000 prostate-specific antigen (PSA) checks using modern diagnostic techniques.

Methods: Men aged 50-70 yr, or 45-70 yr if Black or with a family history of PC, were identified via primary care (general practitioner [GP]) records. Text messages invited men to visit www.talkprostate.co.uk for information on PC and consent to PSA checks coordinated by Medefer, a virtual health care provider. Elevated age-related PSA (40-49 yr: >2.5 ng/ml; 50-59 yr: >3.5 ng/ml, 60-70 yr: >4.5 ng/ml) or a level ≥3 ng/ml triggered referral for multiparametric magnetic resonance imaging (mpMRI) and, if indicated, local anaesthetic transperineal (LATP) biopsy. GPs were informed of the results.

Key findings and limitations: From 137 993 text messages inviting 66 911 individuals, 21 905 (33%) completed online surveys and consented to a PSA check. Of 18 317 men with a PSA result, 865 had elevated PSA (4.7%). After 817 mpMRI examinations, 344 patients underwent biopsy, 263 were diagnosed with PC, and 221 had International Society of Urological Pathology grade group 2-5 PC (84% of those diagnosed, 1.2% of those with a PSA test). The detection rate for grade group 2-5 PC was 26% with the age-related PSA cutoffs, and 25% with the ≥3 ng/ml cutoff. The average PC knowledge score increased by 1.87 points after the survey.

Conclusions and clinical implications: The TPHC programme screened men for PC untested during the COVID-19 pandemic without burdening primary care. Men were targeted from at-risk groups and their awareness was raised. Real-world data demonstrate the detection of significant PC via a modern pathway using MRI and LATP biopsies.

We conducted a post hoc analysis of the EB-StaR study (NCT02993211) to assess the impact of intravesical bacillus Calmette-Guérin (BCG) therapy following en bloc resection of bladder tumour (ERBT) or standard resection (SR) in patients with non-muscle-invasive bladder cancer (NMIBC). The outcome measures were the 1-yr recurrence and progression rates. Among the 276 patients included in the analysis, 1-yr recurrence rates were 33% (95% confidence interval [CI] 21-43%) in the ERBT alone group versus 41% (95% CI 30-50%) in the SR alone group (p = 0.02); and 5% (95% CI 0-14%) in the ERBT + BCG group versus 26% (95% CI 5.8-42%) in the SR + BCG group (p = 0.059). The 1-yr progression rates were 0% in the ERBT alone group versus 2% (95% CI 0-4.6%) in the SR alone group (p = 0.13); and 0% in the ERBT + BCG group versus 5.6% (95% CI 0-16%) in the SR + BCG group (p = 0.4). The combination of ERBT and intravesical BCG therapy appeared to yield excellent oncological control, resulting in a 1-yr recurrence rate of 5% among patients with high-risk NMIBC. Good-quality surgery plus good adjuvant therapy should be considered vital components in optimising long-term oncological outcomes in NMIBC.