Abstract
Background
In addition to the previously studied socioeconomic factors associated with health disparities, insurance status can serve as a prognostic factor associated with overall survival ...in RCC patients (Zhang et al., Future Oncol 2019). Moreover, within this population, having access to health insurance has been reported to result in earlier detection of disease (Javier-DesLoges et al., JAMA Netw Open 2021). In this study, we explored the impact of primary and secondary insurance status on PFS and OS in patients receiving first line systemic therapy for mRCC.
Methods
Patients with mRCC from two NCI-designated comprehensive cancer centers diagnosed between 1990 and 2022 with available insurance information were retrospectively identified using institutional databases. Primary insurance information was categorized into three groups—Medicare, private insurance, and Medicaid/no insurance—while secondary insurance was defined by the presence or absence of secondary coverage. PFS and OS were estimated by Kaplan-Meier method and compared based on insurance status using log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to examine the impact of insurance status on PFS and OS.
Results
In total, 645 patients with mRCC had accessible information and were included in our analysis. Of these, 344 (53.3%), 250 (38.8%), and 51 (7.9%) had primary Medicare, private insurance, and Medicaid/no insurance, respectively. Overall, most patients were male (73.0%), with a median age of 60.0 (22.0-94.0) at time of diagnosis. The most commonly rendered first-line treatments were monotherapy with targeted agents (66.4%), dual immunotherapy (13.6%), and targeted/immunotherapy combinations (10.2%). Median PFS for the entire cohort was 6.6 months (95% CI, 5.9-7.7). Median PFS for patients with primary Medicare was 7.7 months (95%, CI 7.0-9.0), 5.5 months (95% CI, 4.0-7.0) for patients with private insurance, and 4.9 months (95% CI, 3.8-8.1) for Medicaid/uninsured patients. Using an overall log-rank test, a significant difference in PFS among the three groups with different primary insurance was observed (p<0.0001). The median PFS for patients with secondary insurance was 8.1 months (95% CI, 6.6-11.3) compared to 6.1 months (95% CI, 5.5-7.4) for patients without secondary insurance. A multivariate Cox model with adjustment for other factors (such as age, gender, and ethnicity) revealed a statistically significant difference in PFS between patients with and without secondary insurance (p=0.0281). Median OS for the entire cohort was 36.8 months (95% CI, 32.4-44.3). Median OS for patients with primary Medicare, private insurance, and Medicaid/no insurance was 49.0 months (95%, CI 41.8-55.3), 28.5 months (95% CI, 24.1-35.7), and 21.6 months (95% CI, 17.5-42.3), respectively. By an overall log-rank test, a significant difference in OS across the three groups of primary insurance was observed (p=0.0003). No statistically significant differences in OS were observed between patients with and without secondary insurance. Overall, patients with primary Medicare had superior median PFS (p=0.0327) and OS (p=0.0004) compared to those with Medicaid/no insurance; although patients with private insurance had a lower risk of progression and death compared to those with Medicaid/no insurance, the result was not statistically significant.
Conclusions
In this real-world study, we investigated the impact of insurance status on clinical outcomes in patients with mRCC receiving systemic therapy. mRCC patients with primary Medicaid/no insurance or private insurance had inferior median PFS and OS compared to those with primary Medicare. Moreover, patients with secondary insurance had superior PFS over those with primary insurance alone. Overall, our findings suggest that insurance status may serve as a determinant of clinical outcomes. These hypothesis-generating data warrant external validation in prospective studies.
Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). ...Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.
Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model.
A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02).
Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.
Androgen deprivation therapy (ADT) intensification (ADTi) (i.e., ADT with androgen receptor pathway inhibitor or docetaxel, or both) has significantly improved survival outcomes of patients with ...metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of prior ADTi in the mHSPC setting on the disease presentation and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) is not well characterized. In this study, our objective was to compare the disease characteristics and survival outcomes of patients with new mCRPC with respect to receipt of intensified or nonintensified ADT in the mHSPC setting.
In this institutional review board-approved retrospective study, eligibility criteria were as follows: patients diagnosed with mCRPC, treated with an approved first-line mCRPC therapy, and who received either intensified or nonintensified ADT in the mHSPC setting. Progression-free survival (PFS) was defined from the start of first-line therapy for mCRPC to progression per Prostate Cancer Working Group 2 criteria or death, and overall survival (OS) was defined from the start of first-line therapy for mCRPC to death or censored at the last follow-up. A multivariable analysis using the Cox proportional hazards model was used, adjusting for potential confounders.
Patients (n = 387) treated between March 20, 2008, and August 18, 2022, were eligible and included: 283 received nonintensified ADT, whereas 104 were treated with ADTi. At mCRPC diagnosis, patients in the ADTi group were significantly younger, had more visceral metastasis, lower baseline prostate-specific antigen (all p < 0.01), and lower hemoglobin (p = 0.027). Furthermore, they had significantly shorter PFS (median 4.8 vs. 8.4 months, adjusted hazard ratio HR: 1.46, 95% confidence interval 95% CI: 1.07-2, p = 0.017) and OS (median 21.3 vs. 33.1 months, adjusted HR: 1.53, 95% CI: 1.06-2.21, p = 0.022) compared to patients in the nonintensified ADT group.
Patients treated with ADTi in the mHSPC setting and experiencing disease progression to mCRPC had more aggressive disease features of mCRPC (characterized by a higher number of poor prognostic factors at mCRPC presentation). They also had shorter PFS on first-line mCRPC treatment and shorter OS after the onset of mCRPC compared to those not receiving ADTi in the mHSPC setting. Upon external validation, these findings may impact patient counseling, prognostication, treatment selection, and design of future clinical trials in the mCRPC setting. There remains an unmet need to develop novel life-prolonging therapies with new mechanisms of action to improve mCRPC prognosis in the current era.
In a contemporary cohort of previously untreated patients with metastatic renal cell carcinoma, 8.1% had brain metastases. We found that intensive systemic and focal therapies were independently ...associated with better prognosis for patients with brain metastases from renal cell carcinoma.
Patients with brain metastases (BrM) from renal cell carcinoma and their outcomes are not well characterized owing to frequent exclusion of this population from clinical trials. We analyzed data for patients with or without BrM using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). A total of 389/4799 patients (8.1%) had BrM on initiation of systemic therapy. First-line immuno-oncology (IO)-based combination therapy was associated with longer median overall survival (OS; 32.7 mo, 95% confidence interval CI 22.3–not reached) versus tyrosine kinase inhibitor monotherapy (20.6 mo, 95% CI 15.7–24.5; p = 0.019), as were intensive focal therapies with stereotactic radiotherapy or neurosurgery (31.4 mo, 95% CI 22.3–37.5) versus whole-brain radiotherapy alone or no focal therapy (16.5 mo, 95% CI 10.2–21.1; p = 0.028). On multivariable analysis, IO-based regimens (HR 0.49, 95% CI 0.25–0.97; p = 0.040) and stereotactic radiotherapy or neurosurgery (HR 0.48, 95% CI 0.29–0.78; p = 0.003) were independently associated with longer OS, as was IMDC favorable or intermediate risk (HR 0.40, 95% CI 0.24–0.66; p < 0.001). Intensive systemic and focal therapies were associated with better prognosis in this population. Further studies should explore the clinical effectiveness of multimodal strategies.
In a large group of patients with advanced kidney cancer, we found that 8.1% had brain metastases when starting systemic therapy. Patients with brain metastases had significantly poorer prognosis than those without brain metastases. Receipt of combination immunotherapy, stereotactic radiotherapy, or neurosurgery was associated with longer overall survival.
An increased BMI is linked to increased prostate adenocarcinoma incidence and mortality. Baseline tumor gene expression profiling (GEP) can provide a comprehensive picture of the biological processes ...related to treatment response and disease progression. We interrogate and validate the underlying differences in tumor GEP on the basis of BMI in patients with prostate adenocarcinoma.
The inclusion criteria consisted of histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data obtained from treatment-naïve primary prostate tissue. RNA sequencing was performed by a Clinical Laboratory Improvement Amendments-certified laboratory (Tempus or Caris Life Sciences). The Tempus cohort was used for interrogation and the Caris cohort for validation. Patients were stratified on the basis of BMI at the time of prostate cancer diagnosis: BMI-high (BMI
; BMI ≥30) and BMI-low (BMI
; BMI <30). Differential gene expression analysis between the two cohorts was conducted using the DEseq2 pipeline. The resulting GEPs were further analyzed using Gene Set Enrichment software to identify pathways that exhibited enrichment in each cohort.
Overall, 102 patients were eligible, with 60 patients in the Tempus cohort (BMI
= 38, BMI
= 22) and 42 patients in the Caris cohort (BMI
= 24, BMI
= 18). Tumor tissues obtained from patients in the BMI
group exhibited higher expression of genes associated with inflammation pathways. BMI
displayed increased expression of genes involved in pathways such as heme metabolism and androgen response.
Our study shows the upregulation of distinct genomic pathways in BMI
compared with BMI
patients with prostate cancer. These hypothesis-generating data could explain different survival outcomes in both groups and guide personalized therapy for men with prostate cancer.
Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious BRCA1 and/or 2 ...mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of BRCA mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting. Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect. Results: The presence or absence of mutations in the BRCA gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0–232) months. BRCA mutation was present in the patient’s original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% 95% CI, 95.3–99.1%. The adjusted concordance between metastatic samples and cfDNA was 93.5% 95% CI, 86.4–97.3%. Of the patients who had a BRCA mutation detected in their prostate tissue, there was a 70% probability of detecting a BRCA mutation in the patient’s cfDNA as well. For patients who did not have a detectable BRCA mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%. Conclusion: There is a high level of concordance between tissue and blood for BRCA mutations. Testing cfDNA can provide reliable information on BRCA mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new BRCA mutation later in the disease course is a rare event.
Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months ...on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.
The treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, ...and little is known about current treatment approaches and attrition rates for patients with aUC.
To delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample.
This retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis.
Frequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 PD-1/PD-L1 inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line.
Of the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 73.9% men; median age at the start of first-line treatment, 73 IQR, 66-80 years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 30.9%), followed by PD-1/PD-L1 inhibitors (2174 29.9%). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 52.0% and 258 of 857 30.1%, respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 8.1% and 159 of 857 18.6%, respectively), erdafitinib (39 of 2714 1.4% and 28 of 857 3.3%, respectively), and sacituzumab govitecan (14 of 2714 0.5% and 34 of 857 4.0%, respectively).
The findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor-based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.
