Racial Differences in Germline Genetic Testing Completion Among Males With Pancreatic, Breast, or Metastatic Prostate Cancers.

BACKGROUND: Germline genetic testing is a vital component of guideline-recommended cancer care for males with pancreatic, breast, or metastatic prostate cancers. We sought to determine whether there were racial disparities in germline genetic testing completion in this population. PATIENTS AND METHODS: This retrospective cohort study included non-Hispanic White and Black males with incident pancreatic, breast, or metastatic prostate cancers between January 1, 2019, and September 30, 2021. Two nationwide cohorts were examined: (1) commercially insured individuals in an administrative claims database, and (2) Veterans receiving care in the Veterans Health Administration. One-year germline genetic testing rates were estimated by using Kaplan-Meier methods. Cox proportional hazards regression was used to test the association between race and genetic testing completion. Causal mediation analyses were performed to investigate whether socioeconomic variables contributed to associations between race and germline testing. RESULTS: Our cohort consisted of 7,894 males (5,142 commercially insured; 2,752 Veterans). One-year testing rates were 18.0% (95% CI, 16.8%-19.2%) in commercially insured individuals and 14.2% (95% CI, 11.5%-15.0%) in Veterans. Black race was associated with a lower hazard of testing among commercially insured individuals (adjusted hazard ratio [aHR], 0.73; 95% CI, 0.58-0.91; P=.005) but not among Veterans (aHR, 0.99; 95% CI, 0.75-1.32; P=.960). In commercially insured individuals, income (aHR, 0.90; 95% CI, 0.86-0.96) and net worth (aHR, 0.92; 95% CI, 0.86-0.98) mediated racial disparities, whereas education (aHR, 0.98; 95% CI, 0.94-1.01) did not. CONCLUSIONS: Overall rates of guideline-recommended genetic testing are low in males with pancreatic, breast, or metastatic prostate cancers. Racial disparities in genetic testing among males exist in a commercially insured population, mediated by net worth and household income; these disparities are not seen in the equal-access Veterans Health Administration. Alleviating financial and access barriers may mitigate racial disparities in genetic testing.

On-Site Nurse-Led Cancer Genetics Program Increases Cancer Genetic Testing Completion in Black Veterans.

PURPOSE: Telegenetics services can expand access to guideline-recommended cancer genetic testing. However, access is often not distributed equitably to all races and ethnicities. We evaluated the impact of an on-site nurse-led cancer genetics service in a diverse Veterans Affairs Medical Center (VAMC) oncology clinic on likelihood of germline testing (GT) completion. METHODS: We conducted an observational retrospective cohort study of patients who were referred for cancer genetics services at the Philadelphia VAMC between October 1, 2020, and February 28, 2022. We evaluated the association between genetics service (on-site v telegenetics) and likelihood of GT completion in a subcohort of new consults, excluding patients with prior consults and those referred for known history of germline mutations. RESULTS: A total of 238 Veterans, including 108 (45%) seen on site, were identified for cancer genetics services during the study period, with the majority referred for a personal (65%) or family (26%) history of cancer. In the subcohort of new consults, 121 Veterans (54% self-identified race/ethnicity [SIRE]-Black), including 60 (50%) seen on site, were included in the analysis of germline genetic testing completion. In a univariate analysis, patients who were seen by the on-site genetics service had 3.2-fold higher likelihood of completing GT (relative risk, 3.22; 95% CI, 1.89 to 5.48) compared with the telegenetics service. In multivariable regression analysis, the on-site genetics service was associated with higher likelihood of GT completion, but this association was only statistically significant in SIRE-Black compared with SIRE-White Veterans (adjusted RR, 4.78; 95% CI, 1.53 to 14.96; P < .001; P-interaction of race × genetics service = .016). CONCLUSION: An on-site nurse-led cancer genetics service embedded in a VAMC Oncology practice was associated with higher likelihood of germline genetic testing completion than a telegenetics service among self-identified Black Veterans.

Triplet Strategies in Metastatic Clear Cell Renal Cell Carcinoma: A Worthy Option in the First-Line Setting?

Significant strides have been made in the frontline treatment of patients with advanced clear cell renal cell carcinoma (ccRCC). There are multiple standard-of-care doublet regimens consisting of either the combined dual immune checkpoint inhibitors, ipilimumab and nivolumab, or combinations of a vascular endothelial growth factor receptor tyrosine kinase inhibitor and an immune checkpoint inhibitor. Currently, there is an emergence of clinical trials examining triplet combinations. In COSMIC-313, a randomized phase III trial for patients with untreated advanced ccRCC, the triplet combination of ipilimumab, nivolumab, and cabozantinib was compared with a contemporary control arm of ipilimumab and nivolumab. While patients receiving the triplet regimen demonstrated improved progression-free survival, these patients also experienced greater toxicity and the overall survival data are still maturing. In this article, we discuss the role of doublet therapy as standard of care, the current data available for the promise of triplet therapy, the rationale to continue pursuing trials with triplet combinations, and factors for clinicians and patients to consider when choosing among frontline treatments. We present ongoing trials with an adaptive design that may serve as alternative methods for escalating from doublet to triplet regimens in the frontline setting and explore clinical factors and emerging predictive biomarkers (both baseline and dynamic) that may guide future trial design and frontline treatment for patients with advanced ccRCC.

Risk Assessment and Considerations for Proper Management of Elderly Men with Advanced Prostate Cancer: A Systematic Review.

CONTEXT: Treatment decisions for elderly men with prostate cancer are complicated by the intersection of competing risks of cancer, potential complications of treatment, and individual patients' comorbidities. OBJECTIVE: To perform a systematic review of data guiding the assessment of elderly prostate cancer patients that addresses the risk from cancer and treatment, and to discuss a patient-centered approach to incorporating these factors into decision making. EVIDENCE ACQUISITION: Evidence was gathered via a systematic review of the current literature. The search strategy used the terms prostate cancer, elderly, geriatric, >75 yr of age, risk assessment, and treatment in several combinations, and was limited to phase ≥ II clinical trials published between January 2008 and November 2018. Additional supporting literature for the discussion was pulled by hand search. EVIDENCE SYNTHESIS: The benefits of treatment identified for systemic therapies commonly used to treat men with prostate in general extend to elderly patients. Evidence supports a multifaceted assessment of the risks of cancer and aging, and an understanding of the side effects of treatment to optimally guide therapeutic decision making for elderly patients. There is little evidence defining a geriatric risk stratification system specific to prostate cancer, and recommendations are predominantly based on adapted geriatric oncology approaches and expert consensus. CONCLUSIONS: The care of elderly men with prostate cancer should incorporate a review of cancer risk, an assessment of aging, and an understanding of the effects of treatment to provide the patient with thorough and personalized guidance for treatment decisions. Future studies of elderly men with prostate cancer can define and validate ideal risk stratification methods as well as management approaches that may be distinct from those for younger populations. PATIENT SUMMARY: Treatment decisions for elderly men with prostate cancer require consideration of the risk posed by the cancer coupled with an understanding of the patient's general health status.

Quality of Life-Focused Decision-Making for Prostate Cancer.

PURPOSE OF REVIEW: Quality of life (QoL) outcomes have been reported in the literature and incorporated in decision-making in localized prostate cancer management for decades. Until recently, there was less emphasis on understanding the QoL effects of therapies for patients with advanced disease, possibly because there were fewer options for treatment. The purpose of this review is to summarize the key recent literature describing QoL outcomes for prostate cancer treatments in different disease settings. RECENT FINDINGS: Recent data demonstrate that men who undergo local therapy for prostate cancer have worse early QoL related to therapy in sexual, urinary, and bowel function domains compared with men who choose observation, though the effects become less divergent over time. In patients receiving systemic therapy for advanced prostate cancer, more effective treatment typically delays deterioration of various aspects of QoL as assessed by patient-reported outcomes. While there are multiple management options for localized and advanced prostate cancer, different treatment modalities affect QoL in distinct ways. Particularly in settings that lack head-to-head efficacy data between treatment options, clinicians can incorporate adverse effect profiles and effects on patient-reported outcomes describing QoL to inform patients as they make treatment decisions for prostate cancer.

Adjuvant therapy in high-risk prostate cancer.

Although the prognosis in patients with localized prostate cancer is positive overall, high-risk localized disease is responsible for significant cancer-related morbidity and mortality following local treatment failure. Despite recent medical advances in advanced prostate cancer, the role of systemic adjuvant therapy has remained relatively stagnant over the last few decades for patients with high-risk disease, consisting of only androgen deprivation therapy. Novel methods of risk stratification, however, based on traditional clinicopathologic features combined with genomic data, will allow investigators to study adjuvant therapy with more precision in high-risk populations. Additionally, the rise of novel hormonal therapies may provide oncologists with more efficacious drugs in the adjuvant setting, potentially leading to effective adjuvant therapy options for clinicians treating men with high-risk localized prostate cancer.

Revisiting Intermittent Therapy in Metastatic Prostate Cancer: Can Less Be More in the "New World Order"?

CONTEXT: Androgen deprivation therapy (ADT) is the standard of care for men with metastatic hormone-sensitive prostate cancer (HSPC) and a potential treatment option in those with prostate-specific antigen relapse after local therapy. Based on promising biological and preclinical data, several clinical trials compared the efficacy of intermittent androgen deprivation (IAD) versus continuous androgen deprivation (CAD) with the objective of delaying disease progression and improving survival and quality of life (QoL). OBJECTIVE: The objective of this review is to revisit the concept of IAD in the "new world order" and reconsider whether it has a potential clinical role in an era where we have seen unprecedented progress in the management of patients with metastatic HSPC. EVIDENCE ACQUISITION: MEDLINE, Embase, and the Cochrane Library databases were searched for randomized controlled trials comparing IAD and CAD therapies. References of retrieved articles were also searched. Articles with at least 100 randomized patients, which were published in 2008 or later and had data on overall survival or QoL outcomes, were included. EVIDENCE SYNTHESIS: The evidence to date cannot exclude inferiority of IAD compared with CAD with respect to survival outcomes. The hazard ratios in metastatic disease indicate less favorable survival with IAD. No superiority trial conclusively favored IAD or CAD. Two trials demonstrated noninferiority of IAD, although the noninferiority margins (NIMs) are clinically concerning. Another trial could not exclude noninferiority. A modest but temporary QoL and symptom benefit generally favoring IAD was observed. CONCLUSIONS: IAD has not conclusively demonstrated an impact on disease progression or survival, and has only modest effects on QoL and symptoms measured in the short term. As such, it is not the standard of care, particularly in the era where we have seen unprecedented survival impact with combination ADT+docetaxel or abiraterone +prednisone. IAD may need to be reassessed in the context of current therapies, ideally driven by biological rationale, with the goal of minimizing physical and financial toxicities with appropriately designed informative clinical trials. PATIENT SUMMARY: In this report, we looked at two hormone therapy approaches for prostate cancer that is still sensitive to castration: one with treatment breaks and one without. Patients may tolerate therapy with breaks more easily, but this effect is not sustained and is not associated with better longevity. The best longevity is seen in patients who receive newer hormone therapies or chemotherapy in addition to continuous hormone therapy. Whether these newer therapies would be as effective if given intermittently is an important but unanswered question.

Extracapsular extension is associated with worse distant control and progression-free survival in patients with lymph node-positive human papillomavirus-related oropharyngeal carcinoma.

OBJECTIVES: To determine the prognostic utility of pathologic extracapsular extension (ECE) in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Retrospective analysis was performed on patients who underwent surgery for primary HPV-related OPSCC and received adjuvant radiotherapy (RT) between 2006 and 2015. Locoregional control (LRC), distant control (DC), progression-free survival (PFS) and overall survival (OS) were compared between the groups with and without ECE using univariate Kaplan-Meier and multivariate Cox regression survival analyses. RESULTS: 75 patients were identified and ECE was demonstrated on the surgical pathology of 26 patients. ECE(+) patients more frequently received chemotherapy (76.9% vs. 32.7%; p<0.0001) and RT doses>66Gy (76.9% vs. 16.3%; p<0.001). With a median follow-up of 29months, patients with ECE had a significantly worse 5-year DC rate than those without ECE (76.7% vs. 97.9%; p=0.046), and patients with ECE had a significantly worse 5-year PFS (54.5% vs. 93.6%; p=0.021) than those without ECE. On multivariate Cox regression analysis, ECE was independently prognostic of worse DC (hazard ratio: 8.26; 95% confidence interval: 1.24-55.21; p=0.029) and worse PFS(HR: 4.64; 95% CI: 1.18-18.29; p=0.028). There was no statistically significant difference in 5-year LRC (93.3% vs. 95.7%) or OS (66.9% vs. 97.0%) between ECE(+) and ECE(-) patients, respectively. CONCLUSION: This study suggests that ECE is independently prognostic of worse DC and PFS in patients who undergo surgery prior to adjuvant RT for primary HPV-related OPSCC.

Concurrent Diabetes Mellitus may Negatively Influence Clinical Progression and Response to Androgen Deprivation Therapy in Patients with Advanced Prostate Cancer.

OBJECTIVE: To determine if a concurrent diagnosis of diabetes mellitus is associated with worse outcomes in advanced prostate cancer (PC). The effect diabetes may have on the progression of advanced PC is poorly understood. METHODS: Data on 148 advanced PC patients (35 with concurrent diabetes) were collected from an institutional database to obtain diabetic status, data on treatment types and durations, and prostate-specific antigen (PSA) values before, during, and after treatment. Time to castration resistance following the onset of androgen deprivation therapy (ADT) and overall survival (OS) in patients with and without diabetes were compared using univariate Cox regression analyses as the primary endpoints. Differences in PSA response to treatments were compared using chi-squared tests as a secondary endpoint. RESULTS: With a median follow-up of 29 months, time to castration resistance did not differ significantly between patients with and without diabetes who underwent ADT. However, in a subset of patients who received ADT without radiographic evidence of metastases (N = 47), those with diabetes progressed to castration-resistant disease more quickly than those without DM (hazard ratio for progression with diabetes = 4.58; 95% CI: 1.92-10.94; p = 0.0006). Also, a lower percentage of patients undergoing ADT with diabetes had PSA declines of at least 50% (p = 0.17) and reached a nadir PSA <0.2 ng/mL (p = 0.06). OS did not differ based on diabetic status. No differences were seen in response to first-line therapy for castration-resistant prostate cancer. CONCLUSION: Diabetes mellitus may have a detrimental effect on progression of advanced PC, particularly in those patients without radiographic evidence of metastases. Further study is necessary to fully elucidate the effect of diabetes on PC outcomes.

Systemic therapy for the treatment of hormone-sensitive metastatic prostate cancer: from intermittent androgen deprivation therapy to chemotherapy.

Treatment of advanced prostate cancer has changed considerably in recent years, but the vast majority of advances have been made in patients with metastatic castration-resistant disease. There have been relatively fewer advances in the earlier, hormonally responsive stage of metastatic disease. Since the empiric establishment of androgen deprivation therapy as first-line therapy for metastatic prostate cancer decades ago, there have been multiple studies looking at variations of suppressing testosterone, but the overall paradigm has not been strongly challenged until more recently. In particular, the dramatic results reported by the CHAARTED trial not only bring chemotherapy to an arena historically dominated solely by hormonal therapy but also stimulate renewed efforts into improving upon our management of metastatic hormone-sensitive prostate cancer.