Abstract
Cancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified ...screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.
Background
This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials.
Methods
This is an analysis in the NCI ...Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated.
Results
The cohort included 242,720 participants: 197,320 Non‐Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio OR, 0.58; 95% confidence interval CI, 0.50‐0.67; P < .001 and OR, 0.74; 95% CI, 0.64‐0.87; P < .001, respectively), lung (OR, 0.83; 95% CI, 0.76‐0.91; P < .001 and 0.66; 95% CI, 0.57‐0.77; P < .001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79‐0.92; P < .001 and OR, 0.58; 95% CI, 0.51‐0.66; P < .001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07‐%2.32; P < .001), lung (OR, 1.54; 95% CI, 1.38‐1.73; P < .001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04‐1.26; P < .001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09‐3.56; P < .001), colorectal (OR, 2.46; 95% CI, 2.04‐2.96; P < .001), lung (OR, 3.88; 95% CI, 3.20‐4.69; P < .001), and prostate cancer (OR, 1.70; 95% CI, 1.42‐2.04; P = .005).
Conclusions
This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed.
Minorities, women, and the elderly have remained underrepresented in clinical trials in recent years. However, some minority participation has increased in recent years.
CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising ...activity in patients with high-grade non–muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy.
At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies.
Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%–62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%–78%), CIS ± Ta/T1 50% (33%–67%), and pure Ta/T1 33% (8%–70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment–related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment–related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment–related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment–related AEs.
This phase II study demonstrates that intravesical CG0070 yielded an overall 47% CR rate at 6 months for all patients and 50% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS.
•Overall 6-month complete response rate of 47% in patients with high-risk BCG-unresponsive NMIBC.•A 58% 6-month complete response in patients with pure CIS; 50% 6-month complete response for patients with CIS-containing tumors.•Overall toxicity was acceptably low.
Abstract
Background
African American patients with bladder cancer have inferior outcomes compared with non-Hispanic White (White) patients. We hypothesize that access to health care is a primary ...determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer health-care model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database with those receiving care within the equal-access model of the Veterans’ Health Administration (VHA).
Methods
African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer–specific mortality (BCM), and overall survival (OS) were compared by race within each health-care system.
Results
The SEER cohort included 122 449 patients (93.7% White, 6.3% African American). The VHA cohort included 36 322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases, but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio HR = 1.22, 95% confidence interval CI = 1.15 to 1.29) and OS (HR = 1.26, 95% CI = 1.20 to 1.31). In contrast within the VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88 to 1.07) and OS (HR = 0.99, 95% CI = 0.93 to 1.05).
Conclusions
In this study of contrasting health-care models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients.
Open radical cystectomy (ORC) or minimally invasive radical cystectomy with pelvic lymph node (LN) dissection carries significant morbidity to the elderly because they often have several medical ...comorbidities that make a surgical approach more challenging. The objective of this study is to compare robot-assisted radical cystectomy (RARC) and ORC in elderly patients.
A prospective bladder cancer cystectomy database was queried to identify all patients age ≥75 years. A total of 20 patients were identified for each of the RARC and ORC cohorts. A retrospective analysis was performed on these 40 patients undergoing radical cystectomy for curative intent.
Patients in both groups had comparable preoperative characteristics and demographics. Patients had significant medical comorbidities with 80% in each cohort having American Society of anesthesiologists classification of 3 and 50% having had previous abdominal surgery. Complete median operative times for RARC was 461 (interquartile range IQR 331, 554) vs 370 minutes for ORC (IQR 294, 460) (P=0.056); however, median blood loss for RARC was 275 mL (IQR 150, 450) vs 600 mL for ORC (IQR 500, 1925). The median hospital stay for RARC was 7 days (IQR 5, 8) vs 14.5 days for ORC (IQR 8, 22) (P<0.001). The major complication (Clavien≥III) rate for RARC was 10% compared with 35% for ORC (P=0.024). There were two positive margins in the ORC group compared with one in the RARC group with median LN yields of 15 nodes (IQR 11, 22) and 17 nodes (IQR 10, 25) (P=0.560) respectively.
In a comparable cohort of elderly patients, RARC can achieve similar perioperative outcomes without compromising pathologic outcomes, with less blood loss and shorter hospital stays. For an experienced robotic team, RARC should be considered in elderly patients because it may offer significant advantage with respect to perioperative morbidity over ORC.
Background
The safety of active surveillance (AS) for African American men compared with non‐Hispanic White (White) men with intermediate‐risk prostate cancer is unclear.
Methods
The authors ...identified patients with modified National Comprehensive Cancer Network favorable (“low‐intermediate”) and unfavorable (“high‐intermediate”) intermediate‐risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration database. They analyzed definitive treatment, disease progression, metastases, prostate cancer–specific mortality (PCSM), and all‐cause mortality by using cumulative incidences and multivariable competing‐risks (disease progression, metastasis, and PCSM) or Cox (all‐cause mortality) regression.
Results
The cohort included 1007 men (African Americans, 330 32.8%; Whites, 677 67.2%) followed for a median of 7.7 years; 773 (76.8%) had low‐intermediate‐risk disease, and 234 (23.2%) had high‐intermediate‐risk disease. The 10‐year cumulative incidences of definitive treatment were not significantly different (African Americans, 83.5%; 95% confidence interval CI, 78.5%‐88.7%; Whites, 80.6%; 95% CI, 76.6%‐84.4%; P = .17). Among those with low‐intermediate‐risk disease, there were no significant differences in the 10‐year cumulative incidences of disease progression (African Americans, 46.8%; 95% CI, 40.0%‐53.3%; Whites, 46.9%; 95% CI, 42.1%‐51.5%; P = .91), metastasis (African Americans, 7.1%; 95% CI, 3.7%‐11.8%; Whites, 10.8%; 95% CI, 7.6%‐14.6%; P = .17), or PCSM (African Americans, 3.8%; 95% CI, 1.6%‐7.5%; Whites, 3.8%; 95% CI, 2.0%‐6.3%; P = .69). In a multivariable regression including the entire cohort, African American race was not associated with increased risks of definitive treatment, disease progression, metastasis, PCSM, or all‐cause mortality (all P > .30).
Conclusions
Outcomes in the Veterans Affairs Health System were similar for African American and White men treated for low‐intermediate‐risk prostate cancer with AS.
The safety of active surveillance for African American men with intermediate‐risk prostate cancer is unclear. This study has measured similar clinical outcomes for African American men and non‐Hispanic White men treated for either modified National Comprehensive Cancer Network (NCCN) favorable (“low‐intermediate”) or unfavorable (“high‐intermediate”) intermediate‐risk prostate cancer with active surveillance, and it suggests that active surveillance may be an appropriate option for both African American men and non‐Hispanic White men with modified NCCN favorable (“low‐intermediate”) intermediate‐risk prostate cancer.
Active surveillance (AS) is a safe treatment option for men with low-risk, localized prostate cancer. However, the safety of AS for patients with intermediate-risk prostate cancer remains unclear.
We ...identified men with NCCN-classified low-risk and favorable and unfavorable intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration. We analyzed progression to definitive treatment, metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality using cumulative incidences and multivariable competing-risks regression.
The cohort included 9,733 men, of whom 1,007 (10.3%) had intermediate-risk disease (773 76.8% favorable, 234 23.2% unfavorable), followed for a median of 7.6 years. The 10-year cumulative incidence of metastasis was significantly higher for patients with favorable (9.6%; 95% CI, 7.1%-12.5%; P<.001) and unfavorable intermediate-risk disease (19.2%; 95% CI, 13.4%-25.9%; P<.001) than for those with low-risk disease (1.5%; 95% CI, 1.2%-1.9%). The 10-year cumulative incidence of PCSM was also significantly higher for patients with favorable (3.7%; 95% CI, 2.3%-5.7%; P<.001) and unfavorable intermediate-risk disease (11.8%; 95% CI, 6.8%-18.4%; P<.001) than for those with low-risk disease (1.1%; 95% CI, 0.8%-1.4%). In multivariable competing-risks regression, favorable and unfavorable intermediate-risk patients had significantly increased risks of metastasis and PCSM compared with low-risk patients (all P<.001).
Compared with low-risk patients, those with favorable and unfavorable intermediate-risk prostate cancer managed with AS are at increased risk of metastasis and PCSM. AS may be an appropriate option for carefully selected patients with favorable intermediate-risk prostate cancer, though identification of appropriate candidates and AS protocols should be tested in future prospective studies.
Objective The purpose of this study was to analyze the pelvic lymph node dissection (PLND) and margin status using a standard technique in the first 35 patients undergoing robot-assisted radical ...cystectomy (RARC) at our institution while establishing a robotics program, and then to compare the results to the past 35 open radical cystectomy (ORC) performed at our institution. Materials and Methods After obtaining institutional review board approval, we reviewed the clinical and pathologic data from 70 consecutive patients with clinically localized bladder cancer who underwent radical cystectomy with PLND from April 2007 to June 2009. Thirty-five operations were performed open and 35 used the da Vinci robotic system. The PLND was performed in all patients using the same template. Results There was no significant difference between the ORC and RARC group in regards to patient characteristics, tumor stage (43% ORC and 40% RARC having pT3/pT4 disease), and node status (29% N+ in each group). The median total lymph node yield was similar, with 15 (interquartile range IQR 11, 22) in the ORC group and 16 (IQR 11, 24) in the RARC group ( P = 0.5). One patient who underwent RARC had a positive margin compared with 3 patients in the ORC group. Conclusions The initial 35 RARC with PLND performed at our institution compared with the last 35 ORC resulted in equivalent lymph node yield and similar rates of positive margins. RARC with PLND is feasible, safe, and effective when performed at a high-volume center by an experienced team.
To investigate the ability of the prostate genetic score (PGS-33), a germ-line biomarker of prostate cancer (PCa) risk, to categorize men participating in the Prostate, Lung, Colorectal and Ovarian ...(PLCO) Cancer Screening Trial.
We obtained the genetic data from the Cancer Genetic Markers of Susceptibility (CGEMS), a nested case control study examining germ-line DNA in the screened arm of the PLCO trial. A PGS-33 was calculated based on their genotype at 33 PCa associated single nucleotide polymorphisms (SNPs). The primary outcome was the diagnosis of PCa and primary predictor was PGS-33.
We identified 2,244 subjects (no cancer, N = 1017) and cases (N = 1227). The PGS-33 (P<0.001), prostate specific antigen (PSA; P < 0.001), family history of PCa (< 0.001), abnormal digital rectal exam (DRE, P < 0.001), and history of ever smoking (P = 0.037) were associated with a PCa diagnosis. In multivariable analysis, the log (PGS-33) was associated with PCa diagnosis with an odds ratio of 1.68 (95% CI 1.36-2.08, P < 0.001), log (PSA) (OR 8.2; 95% CI 6.75-10.04, P < 0.001), and family history of PCa (OR 2.01; 95% CI 1.26-3.20, P = 0.003). PGS-33 quartiles noted an increasing rate of PCa detection in addition to PSA: 43.2% (Q1), 47.8% (Q2), 58.8% (Q3), and 69.4 (Q4) (P < 0.001) and improvement in PSA performance (P < 0.001).
Germ-line DNA in the form of the PGS-33 is able to risk stratify men regarding their risk of PCa. The PGS-33 may have implications regarding who may benefit most from PCa screening and possibly add to PSA performance.
PDF
