Objectives
To evaluate the effects and utility of intermittent everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex.
Methods
We investigated a total of 26 patients ...with tuberous sclerosis complex who had angiomyolipoma ≥4 cm in diameter. For each patient, we analyzed the reduction in the size of the angiomyolipoma, the change in size after everolimus withdrawal, the size reduction rate on everolimus readministration and adverse events caused by everolimus. The volume of angiomyolipoma was measured using abdominal computed tomography or magnetic resonance imaging. Adverse events were evaluated according to CTCAE v4.0‐JCOG.
Results
The average size reduction rate of angiomyolipoma in the initial treatment with everolimus was 67%. Eight patients (31%) did not have enlarged angiomyolipoma after everolimus withdrawal. The other 18 patients (69%) restarted everolimus treatment because of enlargement of the angiomyolipoma. The average size reduction rate of angiomyolipoma in the everolimus retreatment group was 61%, which was equivalent to the rate for the initial treatment. There were fewer adverse events during everolimus retreatment than in the initial treatment.
Conclusions
This is the first report regarding intermittent everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex. This treatment is effective for tumor control and adverse event management. This beneficial treatment option for patients can minimize the drug dosage and the occurrence of adverse events.
Therapeutic strategies for prostate cancer are currently undergoing a paradigm shift due to the advent of next-generation androgen receptor inhibitors. Among these inhibitors, apalutamide is regarded ...as a key drug because of its effectiveness. However, risk factors for and the timing of the onset of apalutamide-related cutaneous adverse events remain unclear. Therefore, the present study investigated key risk factors for and timing of the onset of apalutamide-related cutaneous adverse events.
Sixty-two Japanese patients with non-metastatic castration-resistant prostate cancer treated with 240 mg/day of apalutamide were enrolled in the present study.
Twenty-four patients (38.7%) developed cutaneous adverse events. Multivariable logistic regression analysis of age, height, and body weight identified body weight as a significant predictive factor for the incidence of cutaneous adverse events (p=0.019). When the mean body weight of patients (63.80 kg) was set as the cut-off value, the Kaplan-Meier analysis revealed that the risk of cutaneous adverse events was significantly increased in those with a body weight <63.8 kg (p=0.003, the log-rank test). The analysis also showed that cutaneous adverse events developed within the first 6 months regardless of body weight.
A lower body weight is a significant risk factor for apalutamide-related cutaneous adverse events and their onset is within 6 months of initiation of therapy.
Salvage lymph node dissection (sLND) for nodal recurrence in prostate cancer (PCa) patients with biochemical recurrence (BCR) is still not recommended in current guidelines, because of the diagnostic ...inaccuracy of current conventional imaging. To assess the performance of
Ga Ga-prostate-specific membrane antigen conjugate 11 positron emission tomography (PSMA-PET) in detecting PCa lymph node metastasis using pathologic confirmation through sLND.
Literature search was conducted using the MEDLINE, SCOPUS, Web of Science, and Cochrane Library on November 11th, 2018 to identify the eligible studies. Studies were eligible if they investigated the diagnostic performance of PSMA-PET before sLND in PCa patients with BCR and reported the number of true positive, false positive, false negative, and true negative on a lesion-based and/or field-based analyses to compare with histopathologic findings in sLND specimens.
Fourteen studies published between 2015 and 2018 comprising 462 patients were selected in this systematic review and meta-analysis. The positive predictive value of PSMA-PET before sLND on a patient-based analysis ranged between 0.70 and 0.93. The pooled sensitivity using lesion-based and field-based analyses were 0.84 (95%CI: 0.61-0.95) and 0.82 (95%CI: 0.72-0.89), respectively. The pooled specificity using lesion-based and field-based analyses were 0.97 (95%CI: 0.95-0.99) and 0.95 (95%CI: 0.70-0.99), respectively. The diagnostic odds ratio using lesion-based and field-based analyses were 189 (95%CI: 39-920) and 82 (95%CI: 8-832), respectively.
PSMA-PET before sLND provided highly accurate performance with clinically relevant high positive and negative predictive values for detecting lymph node disease in patients with BCR after local treatment with curative intent for PCa. PSMA-PET can identify the patients who are likely to benefit from sLND and possibly direct to lesion or region-based dissection.
Objectives
To assess the real‐world clinical benefit of re‐challenging chemotherapy after pembrolizumab in patients with metastatic urothelial carcinoma (mUC), as there have been several reports ...suggesting that programmed cell death protein‐1/programmed death‐ligand 1inhibitors can restore platinum sensitivity.
Patients and Methods
Of 236 patients treated with pembrolizumab, we excluded 45 patients who did not experience progressive disease (PD) for pembrolizumab during the follow‐up and 86 patients who discontinued pembrolizumab by the diagnosis of PD followed by the best supportive care. A total of 105 patients were identified for a logistic regression propensity score model to compare the survival outcomes between patients treated with continuing pembrolizumab (80) and re‐challenging chemotherapy (25) after the diagnosis of PD for pembrolizumab.
Results
A median overall survival (OS) from PD for pembrolizumab was 11 months in 105 patients. Of 25 patients treated with re‐challenging chemotherapy, platinum‐including chemotherapy (gemcitabine and cisplatin; gemcitabine/cisplatin/paclitaxel GCP; methotrexate and vinblastine and adriamycin and cisplatin; and methotrexate and carboplatin and vinblastine MCAVI) was offered in 20 patients (80%). The objective response rate (ORR) for the first‐line chemotherapy in the 105 patients was 30%, with a comparable ORR in 25 patients treated with re‐challenging chemotherapy of 28%. GCP as a re‐challenging regimen was offered in 12 of 25 (48%) patients. The ORR for the GCP regimen was 50%. Propensity score matching was performed using putative clinical factors, from which 34 patients were identified as pair‐matched groups. The OS for patients treated with re‐challenging chemotherapy was significantly longer than continuing pembrolizumab (a median of 13.9 and 5.8 months, respectively: P = 0.048).
Conclusion
Re‐challenging chemotherapy including platinum agents after PD with pembrolizumab offers clinical benefits in patients with mUC.
A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial ...was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (
n
= 25) or placebo with docetaxel and dexamethasone (
n
= 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%;
P
= 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (
P
= 0.018) and CTL (
P
= 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.
Background
There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC).
Materials and methods
We conducted ...a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models.
Results
No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (
N
= 21) and those discontinuing pembrolizumab (
N
= 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months;
P
= 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio HR: 0.21, 95% confidence interval CI: 0.05–0.90,
P
= 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01–0.45,
P
= 0.006).
Conclusions
Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.
Objectives
To determine the biological significance of zonal origins in prostate cancer.
Patients and methods
Altogether, 270 consecutive radical prostatectomy cases from 2009 to 2012 were adopted. ...Cases were divided into those having transition zone (TZ) cancer or peripheral zone (PZ) cancer. Cases with indeterminate tumor location and central zone cancers were excluded from the analyses. Prognosis and clinicopathological features were compared between the two tumor locations. Biochemical recurrence (BCR) and clinical progression (CP) were adopted as prognostic outcome measures. Immunohistochemical features of the v‐ets avian erythroblastosis virus E26 oncogene homolog (ERG)/serine peptidase inhibitor, Kazal‐type 1 (SPINK1) status, and loss of phosphatase and tensin homolog (PTEN‐loss), as well as conventional preoperative and postoperative characteristics, were analyzed.
Results
This cohort comprised 93 cases of TZ cancer and 160 cases of PZ cancer. TZ cancer cases showed significantly higher BCR and CP‐free survival rate than PZ cancer cases. Notably, no TZ cancer cases developed CP during the 7.8 years of median follow‐up time. Tumor location was an independent predictive factor for BCR in the multivariate analysis. Additionally, TZ cancer cases showed a significantly lower prevalence of ERG‐overexpression and PTEN‐loss than PZ cancer cases (3.2% vs 20.1% and 2.2% vs 18.2%, respectively).
Conclusion
TZ cancer cases showed a better prognosis and different immunohistochemical features. Conservative treatment strategies could be considered for TZ cancer cases.
Background
Patients with favorable-risk prostate cancer on active surveillance (AS) are strictly followed for safer execution. Repeat protocol biopsy is essential for evaluating cancer ...aggressiveness. However, the acceptance rate of repeat biopsy is not high enough because of the burdens of biopsy. We assessed the impact of complications after the initial biopsy on repeat protocol biopsy at 1 year using data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study.
Methods
We performed a retrospective analysis using a prospective cohort in the PRIAS-JAPAN study. Patients with favorable-risk prostate cancer (
n
= 856) who consented to participate in the PRIAS-JAPAN study from 2010 to 2018 were enrolled. Follow-up evaluations included regular prostate-specific antigen, digital rectal examination and biopsy. Rates of complications after biopsies and repeat protocol biopsy non-acceptance rate at 1 year were reported. Logistic regression analysis explored the association between the complications after the initial biopsy and repeat protocol biopsy non-acceptance.
Results
Altogether, 759 patients (88.7%) actually proceeded to protocol at 1 year. Repeat protocol biopsy non-acceptance rate at 1 year was 14.9%. Regarding complications after the initial biopsy, hematuria (
p
= 0.028) and pain (
p
< 0.001) rates were significantly higher in the repeat biopsy non-acceptance group, but infection (
p
= 0.056) and hematospermia (
p
= 0.337) rates were not different. On multivariate logistic regression analysis, pain was a significant predictor for repeat protocol biopsy non-acceptance (odds ratio 4.68, 95% confidence interval 1.864–11.75;
p
= 0.001).
Conclusions
Pain at the initial biopsy negatively impacts patients’ compliance with further protocol biopsies during AS.
Purpose
To investigate the prognostic role of the preoperative systemic immune–inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical ...nephroureterectomy (RNU).
Materials and methods
We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS).
Results
Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (
P
= 0.004) and NOC (
P
= 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (
P
= 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (
P
= 0.002), CSS (
P
= 0.002) and OS (
P
= 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all
P
< 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (
P
= 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis.
Conclusions
Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.
The prognostic significance of PSA bounce following definitive radiation therapy remains controversial. To develop a sense of current opinion in this area, we performed a systematic search of the ...literature based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
In January 2021, we systematically searched PubMed, the Cochrane library, and Scopus for studies that compared patients who had localized prostate cancer with or without PSA bounce after definitive radiation therapy. Our objective was to evaluate the association of PSA bounce with biochemical recurrence-free survival, metastatic-free survival, cancer-specific survival, and overall survival, using multivariate Cox regression analysis.
A total of 8881 patients in 10 studies matched the selection criteria for the systematic review and meta-analysis. The number of patients with PSA bounce accounted for 2706 of all 8881 patients (30.5%). PSA bounce was associated with better biochemical recurrence-free survival after definitive radiation therapy (pooled HR: 0.62, 95% CI: 0.54-0.71). Subgroup analyses also showed that PSA bounce was independently associated with decreased risk for biochemical recurrence-free survival in prostate cancer patients treated with low dose rate brachytherapy alone (pooled HR: 0.38, 95% CI: 0.27-0.55) and external beam radiotherapy alone (pooled HR: 0.71, 95% CI: 0.57-0.87).
This meta-analysis indicated that PSA bounce after definitive radiation therapy is related to improved outcome in terms of biochemical failure in prostate cancer patients.
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