In advanced renal cell carcinoma, a transition of drug therapies from cytokines to molecular‐targeted drugs and immune‐oncology drugs provides more clinical benefits to patients, while adequate ...management is required for various and sometimes serious adverse events. At present, the relationship between the pharmacokinetics of many drugs and their effectiveness or adverse events has been elucidated, and therapeutic drug monitoring is being applied to some immunosuppressive, anti‐epileptic and antibacterial drugs in daily clinical practice. Most of the molecular‐targeted drugs used in patients with renal cell carcinoma are orally active, and are affected by absorption and disposition, which can be different for each individual. The monitoring of the circulating drug concentration could be beneficial to patients by providing information for the adjustment of drug dose and the maintenance of a therapeutic plasma concentration range. Genetic polymorphisms are known to be involved in pharmacokinetics, and cause individual differences in clinical efficacy and adverse events. Therefore, a more scientific strategy should be used in regard to the treatment of patients with advanced renal cell carcinoma treated with molecular‐targeted drugs by accumulating evidence on pharmacodynamics and pharmacogenetics.
Accompanied by the development of systemic therapy for metastatic renal cell carcinoma, the concept of focal treatment, including surgical treatment, has been changing. Although immediate ...cytoreductive nephrectomy was essentially considered for synchronous metastatic renal cell carcinoma patients, the CARMENA trial and SURTIME trial revealed the negative impact of immediate cytoreductive nephrectomy. Therefore, immediate cytoreductive nephrectomy is currently considered only for a limited number of patients. Besides, deferred cytoreductive nephrectomy seems to have efficacy for overall survival in prior retrospective studies. Two randomized controlled trials, the PROBE trial (NCT04510597) and the NORDIC‐SUN trial (NCT03977571), are underway to elucidate deferred cytoreductive nephrectomy. Metastasectomy is also considered in metastatic renal cell carcinoma patients because previous studies demonstrated the overall survival benefit of metastasectomy. However, since all reports were retrospective studies, physicians could exclude the patients who were not expected to show the efficacy of metastasectomy. Therefore, an adequate patient selection for metastasectomy is important. A common factor predicting better overall survival was complete resection. Radiotherapies for metastatic lesions during systemic therapy showed approximately 90% local disease control rate at 1 year. However, no report has demonstrated that radiotherapy improves survival so far. Since surgical and focal treatments for metastatic renal cell carcinoma patients generally have minimal evidence, further investigations are needed.
Background
The decline of health-related quality-of-life (QOL) during the year after radical prostatectomy is severe. General self-efficacy (GSE) is an effective psychological factor for long-term ...regulation of patient behavior and emotions. GSE is expected to facilitate enhanced health-related quality of life. We evaluated changes in GSE and analyzed the relationship between GSE and prostate cancer-specific and general health-related QOL.
Methods
We conducted a longitudinal survey with 104 patients who underwent radical prostatectomy and administered the General Self-efficacy Scale (GSES), Expanded Prostate Cancer Index Composite (EPIC), and SF8 Health Survey (SF-8). ANCOVA was performed to compare EPIC and SF-8 between GSES high and low-medium groups.
Results
GSES scores increased significantly after 6 months. Regarding EPIC urinary summary scores, high GSES group was significantly higher than low-medium group at 1 month (mean score difference MSD, 7.3; 95% CI 1.1–13.2,
P
= 0.016), 3 months (MSD, 6.8; 95% CI 0.7–12.8,
P
= 0.028), and 6 months (MSD, 6.3; 95% CI 0.9–11.7,
P
= 0.022). High GSES group had significantly higher SF-8 physical component summary score at 6 months (MSD, 3.2; 95% CI 1.4–5.0,
P
= 0.001), and significantly higher SF-8 mental component summary score at 1 month (MSD, 2.6; 95% CI 0.4–4.9,
P
= 0.022), 3 months (MSD, 2.7; 95% CI 0.8–4.6,
P
= 0.007), and 6 months (MSD, 2.8; 95% CI 1.0–4.6,
P
= 0.003).
Conclusion
This study suggests that high GSE was associated with better prostate cancer-specific and general health-related QOL after radical prostatectomy.
Background
The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in ...patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan.
Methods
Patients with locally advanced or metastatic UC that had not progressed with 4–6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and safety.
Results
In Japanese patients (
n
= 73) randomized to avelumab + BSC (
n
= 36) or BSC alone (
n
= 37), median OS was 24.7 months (95% CI, 18.2-not estimable) vs 18.7 months (95% CI, 12.8–33.0), respectively (HR, 0.81 95% CI, 0.41–1.58), and median PFS was 5.6 months (95% CI, 1.9–9.4) vs 1.9 months (95% CI, 1.9–3.8), respectively (HR, 0.63 95% CI, 0.36–1.11). In the avelumab + BSC and BSC-alone arms, grade ≥ 3 treatment-emergent adverse events (AEs) occurred in 50.0% vs 8.1%, including grade ≥ 3 treatment-related AEs in 13.9% vs 0%, respectively. Efficacy and safety results in Japanese patients were generally consistent with findings in the overall trial population.
Conclusion
Avelumab 1L maintenance treatment showed a favorable benefit-risk balance in Japanese patients, supporting avelumab 1L maintenance as a new standard of care in Japanese patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy.
Trial registration
Clinicaltrials.gov NCT02603432.
Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of ...FGFR4 CN amplification in ccRCC.
The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931.
60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model.
FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.
Background
This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by ...International Metastatic RCC Database Consortium (IMDC) risk criteria.
Methods
We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method.
Results
Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months,
p
< 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months,
p
< 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29–0.93,
p
= 0.03) and in patients with IMDC poor risk (0.26, 0.11–0.59,
p
< 0.01).
Conclusions
Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.
Early diagnosis of urological diseases is often difficult due to the lack of specific biomarkers. More powerful and less invasive biomarkers that can be used simultaneously to identify urological ...diseases could improve patient outcomes. The aim of this study was to evaluate a urological disease‐specific scoring system established with a machine learning (ML) approach using Ig N‐glycan signatures. Immunoglobulin N‐glycan signatures were analyzed by capillary electrophoresis from 1312 serum subjects with hormone‐sensitive prostate cancer (n = 234), castration‐resistant prostate cancer (n = 94), renal cell carcinoma (n = 100), upper urinary tract urothelial cancer (n = 105), bladder cancer (n = 176), germ cell tumors (n = 73), benign prostatic hyperplasia (n = 95), urosepsis (n = 145), and urinary tract infection (n = 21) as well as healthy volunteers (n = 269). Immunoglobulin N‐glycan signature data were used in a supervised‐ML model to establish a scoring system that gave the probability of the presence of a urological disease. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). The supervised‐ML urologic disease‐specific scores clearly discriminated the urological diseases (AUC 0.78–1.00) and found a distinct N‐glycan pattern that contributed to detect each disease. Limitations included the retrospective and limited pathological information regarding urological diseases. The supervised‐ML urological disease‐specific scoring system based on Ig N‐glycan signatures showed excellent diagnostic ability for nine urological diseases using a one‐time serum collection and could be a promising approach for the diagnosis of urological diseases.
Early diagnosis of urological diseases is often challenging. We established a supervised‐ML urological disease‐specific scoring system by obtaining serum Ig N‐glycan signature in a large series of patients from multiple Japanese hospitals. This could be a promising approach for the diagnosis of urological diseases.
Purpose
Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated.
Methods
The ...medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan–Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors.
Results
Median follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients.
Conclusion
In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients.
Purpose
Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, ...this study was aimed at evaluating nivolumab’s efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years.
Methods
From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups.
Results
The median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%;
P
= 0.367), PFS (HR 0.74, 95% CI 0.37–1.51;
P
= 0.414), and median OS (HR 1.29, 95% CI 0.68–2.46;
P
= 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%;
P
= 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%;
P
= 0.535).
Conclusions
Nivolumab’s effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.
This issue 31‐4 Tsuchiya, Norihiko
International journal of urology,
April 2024, 2024-Apr, 2024-04-00, 20240401, Letnik:
31, Številka:
4
Journal Article
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