Abstract
Introduction: Somatic and germline testing are now recommended for patients with advanced prostate cancer. Though referrals for genetic testing have increased since 2017 along with ...developments in National Comprehensive Cancer Network guidelines, genomic profiling in select cancers remains low, with a reported 50% to 80% of eligible patients not completing testing. This study aims to quantify race-associated disparities in both referrals to genetic counseling and completion of genetic testing in patients with advanced prostate cancer. Methods: Henry Ford Health’s electronic medical record (Epic) was queried to identify patients diagnosed with stage III or stage IV prostate cancer between Q1 2017 and Q2 2022. Demographics, site of referral, completion of counseling referrals, and completion of somatic and/or germline testing were identified. Incidence and completion of referral were calculated. Population comparisons were performed with Chi-squared testing. Results: Out of 4,505 unique patients diagnosed with prostate cancer, 919 patients were diagnosed with stage III prostate cancer and 468 patients were diagnosed with stage IV prostate cancer. Black patients had a higher incidence of stage IV versus stage III cancer compared to non-Hispanic whites (NHWs) (31.84% versus 24.92%, P-Value = 0.0042). In stage IV prostate cancer, Black patients were more likely to receive referrals to genetic counseling compared to NHWs (32.2% versus 21.1%, P-Value = 0.011). Black patients were more likely to have a referral placed from the main campus (downtown cancer institute) versus community clinics (suburban) compared to white patients (80.0% versus 50.8%, P-Value = 0.0018). There were no statistically significant differences in completion of testing between the downtown and suburban campuses (67.1% and 61.9%), completion of referral between Black and White patients (48.8% and 43.3%), completion of any genetic testing (66.7% and 64.2%), or completion of germline testing (51.1% and 58.2%). Patients with stage IV prostate cancer who completed their genetic counseling referral were more likely to complete a form of genetic testing (P-Value <0.00001) compared to those who did not present to a genetic counselor. Conclusion and Discussion: Black patients were more likely to present with stage IV disease and more likely to receive a referral to genetic counseling. Though testing completion rates were not significantly different between Black and White patients, overall referral, completion of referral, and testing completion rates remain low in the entire population. Increased indications for testing provide an opportunity for improved referral rates. The statistically significant increase in completed testing by patients who completed their genetic counseling referral reflects both the importance of counseling for optimizing care and stresses the implication that there are significant barriers to patient access that are worth studying further. Additional assessment is underway to better understand both provider- and patient-based barriers to genetic testing.
Citation Format: Kyle McElyea, James Purtell, Mohammed Baseer, Avery Ralston, Maria Jamil, Brigid Jacob, Clara Hwang. Assessment of disparities in completion of genetic testing in patients with advanced prostate cancer abstract. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A066.
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Background: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis, progression, and metastasis in preclinical models. While studies have identified recurrent molecular ...alterations in the Wnt signaling components in about 20% of aPC pts, the clinical significance of these alterations has been incompletely characterized. Methods: PROMISE is a multi-institutional, retrospective, clinical-genomic database - inclusive of aPC pts who had tissue and/or blood-based genomic testing by commercially available CLIA-certified platforms. We evaluated outcomes in pts with alterations leading to the activation of the canonical Wnt pathway, specifically activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 (Wnt altered), compared to those lacking such alterations (Wnt wild type). Multiple endpoints were evaluated, including the frequency of metastatic disease to different sites and co-occurring alterations. Results: 1596 pts with aPC were included with a median age of 63 years at diagnosis. Wnt pathway alterations were identified in 12.4% (198/1596). Wnt altered pts had a statistically significant increase in liver and lung metastases compared with Wnt wild type pts at diagnosis (4.5% vs 2.1%, p=0.0438; 6.1% vs 2.9%, p=0.0292), at first metastatic disease (11.6% vs 5.4%, p= 0.0015; 14.8% vs 6.6%, p<0.0001), and at diagnosis of CRPC (14.2% vs 7.9%, p=0.01436; 16.1% vs 6.8%, p=0.0003). Fewer Wnt altered pts had bone metastases at CRPC compared with wild type pts (67.7% vs 75.2%, p=0.04948) without significant difference of bone metastases at the time of diagnosis or at the time of first metastatic disease. The frequency of metastases to other sites was similar between the cohorts. More Wnt altered pts had ductal features on histology at diagnosis compared with Wnt wild type pts (4.0% v 1.6%, p=0.02415) without difference in PSA, Gleason score, TNM stage, or presence of neuroendocrine or intraductal features. Co-occurring genomic alterations that were more common in Wnt altered pts included PTEN loss/mutation (25.3% vs 18.3%, p=0.0270), RB1 loss/mutation (10.6% vs 5.8%, p=0.0079), AR mutations or gain (37.9% vs 24.0%, p< 0.0001), and SPOP mutations (14.1% vs 3.9%, p< 0.0001) as compared with Wnt wild type pts. Conclusions: Wnt pathway alterations were associated with ductal histology, an increase in visceral metastases at all time points evaluated, and an increase in co-occurring PTEN, RB1, AR, and SPOP alterations. The clinical heterogeneity of aPC and differences in co-occurring mutations between the cohorts make isolating the effect of alterations in a single pathway challenging. Analysis of overall survival outcomes is currently in process, and future multivariable analysis is planned to adjust for established clinical factors and co-occurring mutations to identify the independent contributions of Wnt alterations to clinical outcomes.
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Background: Black men have been underrepresented in large-scale molecular prostate cancer (PC) surveys, despite having higher PC incidence and mortality. Since molecular profiling to guide the ...use of targeted agents is increasingly important in mCRPC, we compared precision medicine data and utilization in a cohort of black and white men with mCRPC. Methods: The PROMISE precision medicine database is an academic collaboration to compile clinical and genomic data from men with PC. All patients have had germline and/or somatic genetic testing performed. Eligibility criteria for this analysis included a diagnosis of mCRPC with available race and biomarker data. The primary outcome was the proportion of non-Hispanic black (NHB) and non-Hispanic white (NHW) men with actionable molecular data, defined as the presence of mismatch repair deficiency (MMRd/MSI-H), homologous recombination repair deficiency (HRRd), tumor mutational burden (TMB) ≥ 10 mut/MB, or AR-V7. Secondary outcomes included the proportion of NHB and NHW men with other alterations, the type and timing of genomic testing performed, and the use of targeted therapy. Results: A total of 962 mCRPC patients (21.2% NHB; 78.8% NHW) met inclusion criteria of 1619 in the overall database. Median age (NHB/NHW) was 61/63; 77.5/68.8% had Gleason 8-10; 52.5/56.7% presented with de novo metastatic disease (33.8/29.9% LN, 36.2/32.2% bone and 8.3/6.1% viscera). The median time from diagnosis to first molecular result was 56.3 mo for NHB v 58.7 mo for NHW (p = 0.45). Use of blood-based molecular testing was more common in NHB men (48.7% v 36.4%, p < 0.001). Overall, 32.8% of NHB men harbored actionable molecular data compared to 30.3% of NHW men (Table). MMRd/MSI-H was more common in NHB men (9.1 v 4.9%, p = 0.04). Other than PTEN (12.7/23.8% NHB/NHW, p = 0.0001), no significant differences were seen in the 15 most frequently mutated genes, including TP53, AR, CDK12, RB1, and PIK3CA. Tumor suppressor co-mutations (PTEN/TP53/RB1) were found in 13.1% of NHB and 18.0% NHW (p = 0.13). Delivery of targeted therapy was reported in 19.6% of NHB and 23.7% of NHW men (p = 0.25) after a median of 2 CRPC lines. Median OS from development of mCRPC was 41.5 mo (95% CI, 34.7-51.3) and 44.7 mo (95% CI, 41.1-51.5) for NHB and NHW men, respectively (p = 0.14). Conclusions: In a real-world mCRPC molecular profiling cohort, we found similar overall rates of actionable molecular alterations in NHB and NHW men, but higher rates of MMRd/MSI-H and lower frequency of PTEN alterations in NHB men. We did not find differences in delivery of targeted therapy. Table: see text
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Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with ...morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate CFR, mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary 17%, diabetes mellitus 16%, cardiovascular 19%, renal 21%), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity; and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials. Table: see text
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Background: Patients (pts) with thoracic cancers have a high rate of hospitalization and death from COVID-19. Smoking has been associated with increased risk for severe COVID-19. However, ...there is limited data evaluating the impact of smoking recency on COVID-19 severity in pts with cancer. We aimed to characterize the clinical outcomes of COVID-19 based on the recency of smoking in pts with thoracic cancers (TC) and all other cancers (OC). Methods: Adult pts with cancer and lab-confirmed SARS-CoV-2 and smoking history recorded in the CCC19 registry (NCT0435470) were included. Pts were stratified by cancer type (TC or OC) and further stratified into subgroups based on the recency of smoking cessation: current smoker; former smokers who quit < 1 yr. ago; 1-5 yr. ago; 6-10 yr. ago; quit > 10 yr. ago; and never smoker. 30-day all-cause mortality was the primary endpoint. Secondary endpoints were any hospitalization; hospitalization with supplemental O2; ICU admission; and mechanical ventilation. Results: From January 2020 to December 2021, 752 pts from TC group and 8,291 pts from OC group met the inclusion criteria. 78% of patients in TC group ever smoked compared to 36% patients in the OC group. In both groups, the majority of never-smokers were females (70% and 60% in TC and OC respectively). The burden of smoking and the rate of pulmonary comorbidities (PC) was higher in the TC group (PC 22-69%) compared to OC group (PC 12-26%) across all smoking strata. Overall, 30-day all-cause mortality was 21% and 11% in pts with TC and OC respectively. Former smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19 outcomes. However, in the OC group, there was no consistent trend of higher mortality or severe COVID-19 outcomes in specific subgroups based on smoking recency. Conclusions: To our knowledge this is the largest study evaluating the effect of granular phenotypes of smoking recency on COVID-19 outcomes in pts with cancer. Recent smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19. Further analysis exploring the factors (e.g., smoking pack years) associated with severe outcomes in this subgroup is planned.Table: see text
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Background: Most patients with cancer and COVID-19 will survive the acute illness. The longer-term impacts of COVID-19 on patients with cancer remain incompletely described. Methods: Using ...COVID-19 and Cancer Consortium registry data thru 12/31/2021, we examined outcomes of long-term COVID-19 survivors with post-acute sequelae of SARS-CoV-2 infection (PASC aka “long COVID”). PASC was defined as having recovered w/ complications or having died w/ ongoing infection 90+ days from original diagnosis; absence of PASC was defined as having fully recovered by 90 days, with 90+ days of follow-up. Patients with SARS-CoV-2 re-infection and records with low quality data were excluded. Results: 858 of 3710 of included patients (23%) met PASC criteria. Median follow-up (IQR) for PASC and recovered patients was 180 (98-217) and 180 (90-180) days, respectively. The PASC group had a higher rate of baseline comorbidities and poor performance status (Table). Cancer types, status, and recent anticancer treatment were similar between the groups. The PASC group experienced a higher illness burden, with more hospitalized (83% vs 48%); requiring ICU (29% vs 6%); requiring mechanical ventilation (17% vs 2%); and experiencing co-infections (19% vs 8%). There were more deaths in the PASC vs recovered group (8% vs 3%), with median (IQR) days to death of 158 (120-272) and 180 (130-228), respectively. Of these, 9% were attributed to COVID-19; 15% to both COVID-19 and cancer; 15% to cancer; and 23% to other causes. Conversely, no deaths in the recovered group were attributed to COVID-19; 57% were attributed to cancer; and 24% to other causes (proximal cause of death unknown/missing in 38% and 19%, respectively). Cancer treatment modification was more common in the recovered group (23% vs 18%). Conclusions: Patients with underlying comorbidities, worse ECOG PS, and more severe acute SARS-CoV-2 infection had higher rates of PASC. These patients suffered more severe complications and incurred worse outcomes. There was an appreciable rate of death in both PASC and non-PASC, with cancer the dominant but not only cause in fully recovered patients. Further study is needed to understand what factors drive PASC, and whether longer-term cancer-specific outcomes will be affected.Table: see text
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Background: Limited information exists regarding the severity of short-term outcomes among patients with gynecologic cancer who are infected with SARS-CoV-2. Methods: Patients with gynecologic ...cancer and laboratory confirmed SARS-CoV-2 infection were identified from the international CCC19 registry. We estimated odds ratios (OR) from ordinal logistic regression for associations with severity of COVID-19 outcomes, defined from least to most severe as hospitalization, intensive care unit (ICU) admittance, mechanical ventilation, and 30-day mortality. Results: Of 842 patients identified, 48% had endometrial cancer, 24% had ovarian cancer, 22% had cervical cancer, and 6% had dual primary/other gynecologic cancers. The majority were from the United States (86%), most were non-Hispanic White (46%), and the median age was 62 years (IQR 52-72). The majority were diagnosed with localized disease (68%); only 18 (2%) and 15 (2%) were fully or partially vaccinated, respectively. In the 3 months prior to COVID-19, 36% had any cancer treatment, with chemotherapy the most common (23%). When diagnosed with COVID-19, most patients were in remission (50%), while 37% had active disease, including 22% with metastatic disease. Most patients presented with typical COVID-19 symptoms (76%); few had a poor ECOG performance status (PS ≥2, 14%). Outcomes included hospitalization (50%), ICU admittance (12%), mechanical ventilation (8%), and death within 30 days of testing positive for SARS-CoV-2 (10%). In unadjusted models, increasing age (OR: 1.03 1.02-1.04) and Black race (OR 1.91, 1.31-2.77) were associated with increased severity of COVID-19 outcomes. Compared to patients in remission for ≥5 years, those with progressive disease had increased severity (OR 1.88, 1.25-2.82), while those in remission for < 5 years or with stable disease had decreased severity of COVID-19 outcomes (OR 0.55, 0.39-0.76). In multivariable models that included adjustment for age, race, and cancer status, additional factors associated with increased COVID-19 outcome severity included cardiac (OR 1.57, 1.13-2.19) and renal (OR 2.00, 1.33-3.00) comorbidities, an ECOG PS ≥2 (OR 5.15, 3.21-8.27), having pneumonia or pneumonitis (OR 4.08, 2.94-5.66), venous thromboembolism (OR 4.67, 2.49-8.75), sepsis (OR 14.2, 9.05-22.1), or a co-infection within ±2 weeks of SARS-CoV-2 (OR: 4.40, 2.91-6.65); asymptomatic SARS-CoV-2 infection was associated with decreased severity of outcomes (OR: 0.25, 0.16-0.38). The overall case fatality rate was 15.7%. Conclusions: Patients with gynecologic cancer experience significant morbidity and mortality related to infection with SARS-CoV-2. Age, race, cancer status, co-morbidities, and COVID-19 complications were associated with more severe COVID-19 outcomes, along the continuum from least to most, of hospitalization, ICU admittance, mechanical ventilation, and 30-day mortality.
Purpose
Generalizable, updated, and easy‐to‐use prognostic models for patients with metastatic castration‐resistant prostate cancer (mCRPC) are lacking. We developed a nomogram predicting the overall ...survival (OS) of mCRPC patients receiving standard chemotherapy using data from five randomized clinical trials (RCTs).
Methods
Patients enrolled in the control arm of five RCTs (ASCENT 2, VENICE, CELGENE/MAINSAIL, ENTHUSE 14, and ENTHUSE 33) were randomly split between training (n = 1636, 70%) and validation cohorts (n = 700, 30%). In the training cohort, Cox regression tested the prognostic significance of all available variables as a predictor of OS. Independent predictors of OS on multivariable analysis were used to construct a novel multivariable model (nomogram). The accuracy of this model was tested in the validation cohort using time‐dependent area under the curve (tAUC) and calibration curves.
Results
Most of the patients were aged 65–74 years (44.5%) and the median (interquartile range) follow‐up time was 13.9 (8.9–20.2) months. At multivariable analysis, the following were independent predictors of OS in mCRPC patients: sites of metastasis (visceral vs. bone metastasis, hazard ratio HR: 1.24), prostate‐specific antigen (HR: 1.00), aspartate transaminase (HR: 1.01), alkaline phosphatase (HR: 1.00), body mass index (HR: 0.97), and hemoglobin (≥13 g/dl vs. <11 g/dl, HR: 0.41; all p < 0.05). A nomogram based on these variables was developed and showed favorable discrimination (tAUC at 12 and 24 months: 73% and 72%, respectively) and calibration characteristics on external validation.
Conclusion
A new prognostic model to predict OS of patients with mCRPC undergoing first line chemotherapy was developed. This can help urologists/oncologists in counseling patients and might be useful to better stratify patients for future clinical trials.
Abstract
Introduction: Reports suggest worsened outcomes in patients with cancer (pts) and COVID-19 (Cov), varying by geography and local peak dynamics. We describe characteristics and clinical ...outcomes of pts with and without Cov.
Methods: RWD at 2 Midwestern health systems from the Syapse Learning Health Network were used to identify adults with active cancer (AC) or past history of cancer (PHC). AC pts were identified by encounters with ICD-10 code for malignant neoplasm or receipt of an anticancer agent within 12 months prior to February 15, 2020; PHC pts were identified by encounters with an active cancer code from May 15, 2015 to February 15, 2019 and no receipt of anticancer therapy within the prior 12 months. Cov was defined by diagnostic codes and laboratory results from February 15 to May 13, 2020. Comorbidities were assessed prior to February 15, 2020; hospitalizations (hosp), invasive mechanical ventilation (IMV), and all-cause mortality (M) were assessed from February 15 to May 27, 2020.
Results: We identified 800 pts with Cov (0.5%) out of a total of 154,585 pts with AC or PHC. Compared to AC pts without Cov (AC WO, 39,402), AC pts with Cov (AC Cov, 388) were more likely to be non-Hispanic Black (NHB, 39% vs. 9%), have renal failure (RF, 24% vs. 12%), cardiac arrhythmias (33% vs. 19%), congestive heart failure (CHF, 16% vs. 8%), obesity (19% vs. 14%), pulmonary circulation disorder (PCD, 9% vs. 4%), and a zip code with median annual household income (ZMI) <$30k (18% vs. 5%). Comorbidity and income were similarly distributed for PHC pts with Cov (PHC Cov, 412). Compared to PHC pts without Cov (PHC WO, 114,383), coagulopathy (coag) was more common in PHC Cov pts (10% vs. 5%). Hosp for AC Cov pts was higher than for AC WO pts (81% vs. 15%). Hosp for PHC Cov pts was also higher than for PHC WO pts (68% vs. 6%). Hosp was highest for NHB pts in both AC Cov and PHC Cov groups (88% and 72%) and for AC Cov pts in low ZMI (94% in <$30K). Pts <50 years old had hosp rates of 79% (AC Cov) and 49% (PHC Cov). IMV rate for AC Cov pts was higher than for PHC Cov pts (21% vs. 14%). Rates of IMV for AC Cov pts were highest in low ZMI (27%) and in pts with coag (36%). M by group was: AC Cov 16%; AC WO 1%; PHC Cov 11%; PHC WO 1%. Among AC Cov pts, M was higher for men (19% vs. 13%) and pts with PCD (31%), RF (25%), or diabetes (DM, 24%); among PHC Cov pts, M was also higher for men (14% vs. 8%) and pts with coag (30%), valvular disease (27%), or PCD (24%). Increasing age, DM, RF, and PCD were associated with increased risk of M for AC Cov pts in age, race/ethnicity, and comorbidity-adjusted logistic regression; increasing age and coag were associated with M in PHC Cov pts.
Conclusion: In this rapid characterization from RWD, pts with Cov have higher rates of pre-existing cardiopulmonary/vascular and renal conditions and increased risk of hospitalization, IMV, and mortality than pts without Cov. Higher Cov risk and worse outcomes in NHB and lower-income pts suggest health care disparities. Whether these outcomes are due to comorbidities or acute sequelae merits further study, as does investigation of alternative definitions for real-world populations and outcomes.
Citation Format: Shirish M. Gadgeel, Michael A. Thompson, Monika A. Izano, Clara Hwang, Tom Mikkelsen, James L. Weese, Frank M. Wolf, Andrew Schrag, Sheetal Walters, Harpreet Singh, Jonathan Hirsch, Thomas D. Brown, Paul G. Kluetz. Using real-world data (RWD) from an integrated platform for rapid analysis of patients with cancer with and without COVID-19 across distinct health systems abstract. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S10-02.
