Treatment with low-dose venetoclax monotherapy may be effective in reducing tumor activity in patients with heavily pretreated multiple myeloma or light chain (AL) amyloidosis harboring t(11;14), according to data recently published in the 

Across the study population (n = 25), 44% of patients (n = 11) experienced a partial response (PR) or higher following treatment with venetoclax. Specifically, 71% of patients with AL amyloidosis and 33% of those with multiple myeloma achieved a PR or greater.

The study was conducted to assess the safety and efficacy of single-agent venetoclax, as well as to determine the importance of molecular markers in predicting treatment response. Additionally, potential resistance mechanisms of patients with multiple myeloma harboring t(11;14) were evaluated.

“We believe this study is a significant step towards multiple myeloma treatment by providing ways for selection of the optimal treatment regimens, prognostic biomarker, [resistance] mechanism, and increased understanding of t(11;14) role in multiple myeloma pathogenesis,” Hareth Nahi, MD, senior physician of Karolinska Institutet in Sweden, and coinvestigators wrote in the paper.

The trial enrolled 18 patients who were diagnosed with relapsed multiple myeloma and 7 with relapsed AL amyloidosis, all of whom harbored t(11;14). All patients who enrolled received a 100-mg dose of daily venetoclax for the first 3 days, with an escalation of 100 mg every third day up to a maximum dose of 400 mg daily.

Of the 25 patients who enrolled, 20 had diagnostic bone marrow biopsies available. Among the patients with available biopsies, 8 relapse bone marrow biopsies were examined. RNA sequencing was performed on 37 samples from patients with newly diagnosed multiple myeloma, 10 of which harbored t(11;14).

“The newly diagnosed multiple myeloma samples were obtained from untreated patients, whereas relapsed/refractory patients received standard multiple myeloma treatments,” the authors wrote.

Three subsets of these samples were selected based on the following criteria: 

 cohort (n = 37; newly diagnosed myeloma), 27 non-t(11;14) vs 10 harboring t(11;14); resistance cohort (n = 12), 8 newly diagnosed myeloma vs 4 relapsed/refractory myeloma and all patients with t[11;14] more than 60%; and synergy cohort (n = 12), 2 hyperdiploidy, 7 harboring t(11;14), and 3 harboring hyperdiploidy and t(11;14).”

Forty percent (n = 10) of the patient population were male and the median age was 57 years old (range, 43-80). Thirty percent (n = 7) of the population had stage III disease. In addition to all patients having t(11;14), all patients with multiple myeloma harbored another aberration.

The median follow-up time from the start of treatment was 9 months. All of these patients were treated with a proteasome inhibitor and 96% were given an immunomodulatory drug prior to receiving venetoclax. The median prior lines of therapy was 3 (range, 1-9).

The median time on treatment was 7.2 months, and those who achieved a PR or better were on venetoclax for at least 15 months, with no median reached, compared with 6 months for those who achieved less than a PR.

Twenty patients received immunohistochemistry from bone marrow from diagnosis and even later relapse in some cases. No significant changes were noted in terms of percentage of CD138-positive multiple myeloma cells expressing anti- and pro-apoptotic proteins from diagnosis to relapse or between patients who achieved greater than or less than a PR. However, it was noted that the frequency of 

-expressing cells across analyzed myeloma samples were notably higher (

 = .031), in patients who achieved greater than and less than a PR having an average ratio of 2.7 and 1.0, respectively, following treatment.

Similar data was seen in newly diagnosed myeloma samples (

 = .028). Similar trends were noted in patients with relapsed/refractory disease.

 ratios can be used to predict the venetoclax response in addition to presence of t(11;14),” the authors wrote.

Moreover, an RNA-sequencing analysis of the resistance cohort (n = 12) uncovered 46 differentially expressed genes between diagnosis and relapse, 26 of which were downregulated and 20 of which were upregulated. In total, 65% of the downregulated genes contained binding motifs for an IRF transcription family member in the promoter region.

IRFs motif enrichments were calculated in the promoter regions of downregulated differentially expressed genes and the enrichments were hierarchically sorted based on the adjusted 

 values. Results showed that that the IRF5 motif enrichment ranked the highest [

< .001]. However, IRF5 was not found among the differentially expressed genes,” the authors wrote.

Additionally, investigators correlated the top 3 hierarchically ordered IRFs—IRF5, IRF8, and IRF9—with the expression of 17 differentially expressed genes containing IRF motif; IRF5 ranked at first place.

Although 80% of the study population experienced all-grade treatment-emergent adverse effects, grade 3/4 TEAEs occurred in 52% of patients; all events were considered manageable and no deaths linked with treatment occurred, according to investigators. The most common non-hematologic AE was nausea (32%) with hematologic AEs including neutropenia (28%) and thrombocytopenia (28%).

"The study shows that selection of low dose venetoclax was critical to reduce the [AEs] of the drug without adventuring the benefit of venetoclax in regard to response rates and survival," first author Hareth Nahi, MD, a senior physician and associate professor in the Department of Medicine at the Center for Hematology and Regenerative Medicine, Huddinge, Karolinska Institutet, concluded in a press release.

Nahi H, Kashif M, Klimkowska M, et al. Low dose venetoclax as a single agent treatment of plasma cell malignancies harboring t(11;14). 

New findings provide hope for treatment of multiple myeloma. News release. Karolinska Institutet. May 19, 2021. Accessed May 27, 2021. https://bit.ly/3yTPCj8

This article was originally published on OncLive as 

“Low-Dose Venetoclax Achieves Promising Results in AL Amyloidosis and Myeloma Subsets”

Articles

Overall, 71% of patients with AL amyloidosis and 33% of those with heavily pretreated multiple myeloma achieved a partial response or greater after receiving treatment with low dose venetoclax. 

Low-Dose Venetoclax Induces Antitumor Activity in Subsets of AL Amyloidosis, Myeloma 

A meta-analysis of prostate cancer genome-wide association studies has indicated that germline variation contributes to racial disparities in prostate cancer risk. Individuals of African descent, according to the data, demonstrated a higher mean genetic risk score (GRS) compared to those of European ancestry.

Results showed that the top GRS decile associated with odds ratio was 5.06 for men of European descent (95% CI, 4.84-5.29) and 3.74 for men of African descent (95% CI, 3.36-4.17). When compared with men of European ancestry, men of African ancestry were estimated to have a mean GRS that was 2.18 times higher (95% CI, 2.14-2.22), while men of East Asian ancestry had a mean GRS that was 0.73 times lower (95% CI, 0.71-0.76).

“We not only found new markers of risk, but also demonstrated that, by combining genetic information across populations, we were able to identify a risk profile that can be applied across populations,” said Christopher Haiman, ScD, professor of preventative medicine and AFLAC Chair in Cancer Research at the Keck School of Medicine of USC, and director the USC Center for Genetic Epidemiology.

 “This emphasizes the value of adding multiple racial and ethnic populations into genetic studies.”

Additionally, investigators identified 86 new genetic risk variants, all of which were found to be independently associated with prostate cancer risk, which brings the total known risk variants to 269.

“To understand the aggregate effect of the 269 variants on prostate cancer risk, we constructed a GRS using the multiethnic weights of the risk variants associated with disease,” wrote the study authors. “Compared with men at average genetic risk in the 40% to 60% GRS category, the estimated odds ratio for men in the top 10% of the GRS [90%-100% GRS category] was 5.06 [95% CI, 4.84-5.29] for men of European ancestry, 3.74 [95% CI, 3.36-4.17] for men of African ancestry, 4.47 [95% CI, 3.52-5.68] for men of East Asian ancestry, and 4.15 [95% CI, 3.33-5.17] for Hispanic men. Men in the top 1% of the GRS distribution had higher odds of disease, ranging from 11.65 [95% CI, 10.56-12.85] for men of European ancestry to 5.68 [95% CI, 4.44-7.28] for men of African ancestry.”

Prior research has shown that certain races not only trend towards higher incidences of prostate cancer, but higher rates of disease-related mortality overall. Incidence rates of prostate cancer from 2012 to 2016 indicated that 172.9 non-Hispanic Black men per 100,000 develop prostate cancer compared with 97.2 non-Hispanic White men, 86.8 Hispanic men, 68 American Indian and Alaska Native men, and 52.9 Asian and Pacific Islander men.

Similarly, mortality rates from 2013 to 2017 indicate that 38.7 non-Hispanic Black men per 100,000 died from prostate cancer vs 18.7 American Indian and Alaska Native men, 18 non-Hispanic White men, 15.7 Hispanic men, and 8.6 Asian and Pacific Islander men.

Despite the increased risk of incidence and death seen in Black patients

White patients are often overrepresented in clinical cancer trials

hindering investigators' progress in identifying reasons for these disparities.

This developed the rationale for the meta-analysis, with researchers from the USC Center for Genetic Epidemiology, as well as the Institute for Cancer Research in London, United Kingdom, striving to identify the reasons for these disparities. Investigators compiled data from the majority of global genomic prostate cancer studies, including 234,253 men of different races and ethnicities from the United States, United Kingdom, Sweden, Japan, and Ghana, consisting of 107,247 cases and 127,006 controls.

In what is considered the largest and most diverse genetic prostate cancer analysis, findings point toward genetics playing a role in the disparities seen across different racial groups, which could possibly help physicians apply precision medicine to early prostate cancer detection in the future.

“Our long-term objective is to develop a genetic risk score that can be used to determine a man’s risk of developing prostate cancer,” said Haiman. “Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it’s more treatable.”

Current prostate cancer screening guidelines recommend that men aged 55 years or older with average risk undergo prostate-specific antigen (PSA) testing. Though high PSA levels are indicative of prostate cancer, this method typically detects more indolent tumors, leading to unnecessary treatment, according to investigators.

Additionally, investigators believe that GRS could help to guide more selective PSA testing by helping to identify patients who are at a higher risk for prostate cancer, potentially including high-risk patients younger than 55 years old. A larger clinical trial is needed in order to better translate these findings into improved early prostate cancer detection, investigators noted.

“Most [importantly], unlike previous screening trials, this [study] would need to be more representative of the diversity we see in the world,” Haiman concluded. “No population should get left behind.”

Conti DV, Darst BF, Moss LC, et al. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. 

. 2021;53(65-75). doi:10.1038/s41588-020-00748-0

Largest, most diverse prostate cancer study shows genetic role in health disparities. News release. Keck School of Medicine of the University of Southern California. January 2, 2021. Accessed January 5, 2020. 

Prostate at a glance. American Cancer Society Cancer Statistics Center. Accessed January 5, 2021. 

This article was originally published on OncLive as “

African Ancestry Is Linked With Higher Prostate Cancer Risk Vs European Ancestry

Germline variation may cause men of African descent to have a higher risk of prostate than men of European descent. 

African Ancestry Associated With Increased Prostate Cancer Risk

Although a high body mass index (BMI) has been found to improve survival outcomes among patients with non-small cell lung cancer (NSCLC), a high visceral fat index (VFI) has shown to do the opposite. Data published in the 

, has indicated that high VFI was negatively associated with survival in patients with NSCLC.

As a result, the data suggest that the measurement used to define obesity might influence whether obesity is a risk factor for NSCLC.

An elevated VFI was linked with worse overall survival (OS; HR, 1.84; 95% CI, 1.21-2.81) and recurrence-free survival (RFS; HR, 1.82; 95% CI, 1.06-3.11) in patients with early-stage disease who were undergoing resection. Multivariable modeling confirmed these results indicating that a high VFI is associated with a worse RFS (HR, 1.79; 95% CI, 1.04-3.08) in this population.

Visceral obesity was also found to be associated with changes in the tumor immune microenvironment in patients with late-stage disease. Moreover, obesity exacerbated disease progression, altered gene expression in the tumor immune microenvironment, and attenuated anti-cancer immune responses in mice.

"These findings clarify the truly negative relationship that exists between central obesity and lung cancer outcomes, and they present a viable alternative to the use of BMI in retrospective studies of obesity rooted in biology with clear relevance to cancer outcomes," first author Joseph Barbi, PhD, an assistant professor of oncology and assistant member in the Department of Immunology of Roswell Park, said in a press release.

Thus far, 13 cancer types have been linked with excess body weight, and obesity rates continue to rise within the United States.3,4 Although the association between measures of obesity and cancer incidence and outcome is well understood in other tumors like breast, esophageal, and colon cancer, this correlation is more complicated in lung cancer.

Unlike what has been reported in other cancers, obesity has been associated with reduced incidence of lung cancer. For example, 1 study in which investigators examined the National Institutes of Health—American Association of Retired Persons demonstrated that a high BMI was inversely linked with risk for the disease.5 Controlling for smoking was found to increase the link between this obesity measure and incidence. Other studies have indicated that BMI was linked with better long-term outcomes in this disease.

To gain some clarity on the association between survival with adiposity and NSCLC, investigators set out to measure central obesity in a cohort of patients with stage I NSCLC who were undergoing lobectomy and examine its association with outcomes.

The survival analyses in the trial included data on patients with pathologic stage I and II NSCLC who were undergoing a pulmonary lobectomy at the Roswell Park Comprehensive Cancer Center between October 2008 and December 2015. Investigators included relevant information

from the institutional thoracic surgery database, as well as the medical record. Overall, they examined tumor stage, tumor grade, histology, OS, and RFS data. All confounders were treated as categorical variables, with the exception of age.

VFI was first evaluated as a continuous variable in these studies. In model generation, the following covariates were utilized: age, sex, grade, race, histology, diffusion capacity for carbon monoxide (DLCO), American Society of Anesthesiology (ASA) score, and smoking status.

Investigators conducted univariate analyses to examine the link between individual variables and OS and RFS. Only variables linked with OS and RFS on these analyses were included in the model generation by multivariable analyses. Moreover, because of the link between VFI and age and sex, interaction variables were included in model generation. Both univariate and multivariable analyses were utilized to compare the OS and RFS in these patients.

A total of 554 patients with stage I and II disease were selected for the analysis; investigators were able to collect reliable fat area measurements from 513 of these patients, with 97.3% at L3, 0.9% at L2, and 1.8% at L1. A total of 159 patients with advanced-stage disease who had molecular testing and reliable fat area measurements were included, with 91.8% at L3, 6.3% at L2, and 1.9% at L1.

Inter-observer correlation of VFI measurements were noted to be good (n = 53; R2 = 0.95). Moreover, the correlation of measurements between L2 and L3 levels (n=29; R2 = 0.92; slope = 1.05), as well as L1 and L3 levels (n=28; R2 = 0.85; slope = 1.05) were also determined to be good. Notably, L2 and L1 measures were used when L3 measurements were not available. Computed tomography scans were successfully utilized to identify patients with predominant visceral or subcutaneous adipose tissue distribution.

Additional data revealed that VFI was not linked with BMI (Pearson correlation coefficient = -.006; 

 = .9), although it was linked with sex and age. The mean VFI was higher in males than it was in females, at 0.56 vs 0.37, respectively (

 < .01). Moreover, VFI was noted to elevate with increasing age (Pearson’s correlation coefficient = .32; 

Data from univariate analyses indicated that there was a significant link between sex, ASA score, tumor grade, histology, age, DLCO, and VFI with OS. RFS was also linked with sex, tumor grade, tumor stage, ASA score, and VFI. Multivariable analysis led to a final OS model that retained age, sex, DLCO, ASA score, VFI, tumor grade, and the interaction term between VFI and age. A final RFS model was also produced that retained only tumor grade, tumor stage, and VFI as predictive variables.

Forty-one of the 513 patients had an unknown cause of death, leading investigators to examine disease-specific survival (DSS) in 472 patients. VFI tertile was found to be linked with DSS (HR, 2.1; 

 = .025), but VFI was not statistically significant as a continuous variable (

 = .1). Moreover, VFI tertile was associated with worse DSS (HR = 2.25; 95% CI, 1.16-4.37; 

"Our study provides much needed clarity to the relationship between adiposity and survival [for patients with NSCLC], providing firm scientific justification for the targeting of obesity's pro-tumor effects, which include decidedly adverse effects on the antitumor immune response," Sai Yendamuri, MD, chair of the Department of Thoracic Surgery, professor of oncology, attending surgeon of the Department of Thoracic Surgery, and director of the Thoracic Surgery Laboratory at Roswell Park, stated in the press release.

Barbi J, Patnaik SK, Pabla S, et al. Visceral obesity promotes lung cancer progression – towards resolution of the obesity paradox in lung cancer. 

. 2021;16(8):1333-1348. doi:10.1016/j.jtho.2021.04.020

Research suggests BMI may not be best obesity indicator to assess risk for lung cancer. News release. International Association for the Study of Lung Cancer. June 2, 2021. Accessed July 28, 2021. https://bit.ly/3zM5CTI

Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer—viewpoint of the IARC Working Group.

. 2016;375(8):794-798. doi:10.1056/NEJMsr1606602

Ogden CL, Fakhouri TH, Carroll MD, et al. Prevalence of obesity among adults, by household income and education — United States, 2011–2014. 

. 2017;66(50):1369-1373. doi:10.15585/mmwr.mm6650a1External.

Smith L, Brinton LA, Spitz MR, et al. Body mass index and risk of lung cancer among never, former, and current smokers. 

. 2012;104(10):778-789. doi:10.1093/jnci/djs179

“High Visceral Fat Index Associated With Worse Survival Outcomes in Early-Stage Lung Cancer”

Whether or not obesity should be considered a risk factor for non-small lung cancer might be determined by how it is measured. 

Visceral Fat Index Score Questions Obesity-Survival Connection in Early-Stage Lung Cancer

Patients with favorable-risk prostate cancer were shown to move away from active surveillance following exposure to their Oncotype DX Genomic Prostate Score (GPS), according to data from the ENACT study (NCT02668276) published in the 

These results suggested that patients’ treatment decisions in diverse populations can be influenced through prognostic molecular assessment.

Results regarding treatment choice at the second visit indicated that assignment to the GPS cohort was linked with a marginally lower likelihood of selecting active surveillance compared with immediate therapy (

 = .067). When excluding 10 men who were assigned to GPS and did not receive a test result, the association was found to be slightly stronger (

 = .029). Unadjusted analyses indicated that intervention reduced the relative odds of selecting active surveillance by approximately half.

Moreover, the choice of management approach was found to be closely associated with a change in the urologist's preference of treatment following GPS results. Following the results, preferences changed from active surveillance to treatment 18 times; preference shifted from treatment to active surveillance only 3 times. For controls, urologist preference shifted from active surveillance to treatment only 5 times and only twice from treatment to active surveillance.

Ratings on the Decisional Conflict Scale—which measures a patient's perception of preparedness, support, and uncertainty, ranging from 0 at the lowest and 40 at the highest—did not significantly differ between the control group (mean, 5.56; standard deviation, 7.25) and GPS group (mean, 4.60; standard deviation, 7.17), respectively, (

 = .37). However, differences in scores on the Decision Regret Scale—which ranges from 5 at the lowest and 25 at the highest—were not found to significantly differ between the control group (mean, 7.54; standard deviation, 2.92) and the GPS group (mean, 8.28; standard deviation, 3.38), respectively (

“We completed the first randomized trial, to our knowledge, of a prognostic multigene expression score on initial treatment choice among men with favorable-risk prostate cancer,” lead author Adam B. Murphy, MD, MBA, MSCI, of Feinberg School of Medicine, and his colleagues wrote. “As more biomarkers yielding probability estimates enter the clinic, it is important to understand their impact on cancer treatment choice and decision quality in diverse patient populations.”

Although men with low-risk prostate cancer need to make a choice between receiving immediate therapy or active surveillance with the possibility of deferred treatment, active surveillance is now considered to be a safe alternative for the right population. Although the utilization of active surveillance has increased in the United States over the past several years, its use in Black patients has lagged.

Concerns exist as to whether this strategy is equally safe in this high-risk subset due to differences in biologic aggressiveness of the diseases, reduced compliance due to issues with access to care, and possible undersampling of tumors in the anterior section of the prostate.

After considering these factors, investigators launched a randomized trial in a predominantly Black patient population from 3 public hospitals to assess whether the addition of the Oncotype DX GPS assay to the National Comprehensive Cancer Network (NCCN)–based risk counseling would impact decisionmaking. Investigators theorized that the biomarker would help to improve risk stratification in diverse, high-risk patient populations by detecting aggressive prostate cancer despite reassuring standard clinical measures.

The trial enrolled men with newly diagnosed prostate cancer who were eligible for active surveillance. Additional enrollment criteria included being under the age of 76 years, having an ECOG performance status of 0 to 2, a life expectancy of over 10 years, and a NCCN risk level of favorable intermediate or below.

Based on consensus among participating urologists regarding eligibility for active surveillance, the favorable intermediate definition was slightly modified from NCCN criteria to exclude cases with grade group 2 and over 3 positive cores, and include those with a prostate-specific antigen (PSA) density of 10 ng/mL to 20 ng/mL if PSA density was less than 0.15, 4 unfavorable intermediate cases were included.

During the first visit, patients were diagnosed and given identical counselling regarding treatment options following a diagnostic biopsy. Additionally, during the initial visit, patients were randomized to either the intervention or control arm utilizing a block random assignment scheme, wherein patients were stratified based on trial site and NCCN risk level. From there, standardized instruments were utilized to gather baseline data on comorbidities, urinary and sexual function, health literacy, and psychologic indicators.

Two to 3 weeks later, patients returned for a second visit to discuss their GPS report, if assigned; undergo NCCN-based risk counseling; and make a treatment decision. The third visit would take place 4 weeks after the second and prior to treatment to collect follow-up surveys and assess whether treatment choices had changed.

Lastly, the fourth visit took place following the first clinical encounter after recovering from surgery, completing radiation, or the first active monitoring encounter. Patients were then asked to complete the 10-item Decisional Conflict Scale to assess perceived decision quality during the third visit and validate men with low health literacy who needed to decide about prostate cancer screening. Moreover, patients completed the 5-item Decision Regret Questionnaire at visit 4, which was validated in cohorts who needed to make a decision regarding treatment.

A total of 1315 consecutive patients with positive cancer biopsies were screened, 24% (n = 317) of whom were eligible to participate in the trial. The primary reason patients were ineligible to participate was due to having a risk level above low intermediate risk status. Nine patients had insufficient tumor, and another had excessive inflammation.

Seventy percent of study participants were African American, 16% had a college degree, 46% had a low health literacy, and 12% had private insurance. Eighty-six percent of urologists who participated on the trial were inclined to favor active surveillance immediately prior to the first visit following a diagnosis.

The random assignment carefully balanced key baseline variables except for patients who had a first-degree relative with prostate cancer and men with severe erectile dysfunction. However, severe erectile dysfunction was found to be less common in the interventional cohort. Therefore, particular attention was given as a potential confounder in the analysis.

In the subgroup analysis, GPS results tended to widely vary across risk levels, although investigators noted that there was an association between GPS and pre-test NCCN risk. Moreover, an association was identified between immediate treatment and higher GPS results within risk levels.

Moreover, in multivariable models, low intermediate status was identified as a strong negative predictor for active surveillance vs very low-risk status; low-risk status also had a negative association. Men who had a positive family history of prostate cancer were 4 times more likely to select active surveillance. Those with any health insurance were 3 times more likely to choose active surveillance. Notably, GPS was associated with a 7-fold lower chance of selecting active surveillance in men with a lower health literacy (

When assessing change in NCCN risk following GPS, investigators found that although the intervention effect was independent of baseline risk, 60% of men in the intervention group experienced a shift in NCCN risk following GPS testing. In total, 43% of men who received GPS moved to a higher NCCN risk group, 39% of whom had selected treatment rather than active surveillance. Additionally, 17% of men (n = 15) moved to a lower risk level, 2 of whom selected treatment. All men within the intervention cohort who were very low risk at baseline selected active surveillance, 34% of whom had received GPS results that were consistent with a higher risk level.

When examining changes in treatment choice, 16 men, 10 from the intervention arm and 6 from the control arm, changed their choice of treatment following the second visit, which resulted in the patient receiving a different treatment (

 = .32). Five patients from either arm changed from active surveillance to undecided by their third visit, although they eventually went on to receive active surveillance.

Long-term follow-up on the active surveillance arm is currently ongoing, although among patients who received surgery as their initial therapy, investigators observed negligible differences in adverse pathology following prostatectomy.

Murphy AB, Abern MR, Liu L, et al. Impact of a genomic test on treatment decision in a predominantly African American population with favorable-risk prostate cancer: a randomized trial. 

. 2021;39(15):1660-1670. doi:10.1200/JCO.20.02997

Gray PJ, Lin CC, Cooperberg MR, et al. Temporal trends and the impact of race, insurance, and socioeconomic status in the management of localized prostate cancer. 

. 2017;71(5):729-737. doi:10.1016/j.eururo.2016.08.047

Mahal BA, Butler S, Franco I, et al. Use of active surveillance or watchful waiting for low-risk prostate cancer and management trends across risk groups in the United States, 2010-2015. 

. 2019;321(7):704-706. doi:10.1001/jama.2018.19941.

Yuan J, Kensler KH, Hu Z, et al. Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry. 

. 2020;16(2):e1008641. doi:10.1371/journal.pgen.1008641.

Ha YS, Salmasi A, Karellas M, et al. Increased incidence of pathologically nonorgan confined prostate cancer in African-American men eligible for active surveillance. 

. 2013;81(4):835. doi:10.1016/j.urology.2012.12.046

Abern MR, Bassett MR, Tsivian M, et al. Race is associated with discontinuation of active surveillance of low-risk prostate cancer: results from the Duke Prostate Center. 

. 2013;16:85-90. doi:10.1038/pcan.2012.38

Gökce MI, Sundi D, Schaeffer E, et al. Is active surveillance a suitable option for African American men with prostate cancer? A systemic literature review. 

. 2017;20(2):127-136. doi:10.1038/pcan.2016.56

Jalloh M, Myers F, Cowan JE, et al. Racial variation in prostate cancer upgrading and upstaging among men with low-risk clinical characteristics. 

. 2015;67(3):458-459. doi:10.1016/j.eururo.2014.03.026

Sundi D, Kryvenko ON, Carter HB, et al. Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in Black American men. 

. 2014;191(1):60-67. doi:10.1016/j.juro.2013.06.021

“Genomic Prostate Score Could Impact Treatment Decisions in Diverse Prostate Cancer Populations”

Patients with favorable-risk prostate cancer tended to move away from active surveillance to initiating treatment after receiving their Oncotype DX Genomic Prostate Score.
 


Diverse Patient Population Favors Immediate Therapy After Receiving Genomic Prostate Score

A recent study showed that, among patients with limited-stage small cell lung cancer (LS-SCLC), patients of color had longer overall survival (OS) than White patients, suggesting race is associated with survival in this disease, according to data analysis published in 

Among patients with stage I disease, no significant difference across races was observed (

= .54). The median OS in Hispanic patients was 27.7 months (95% CI, 19.4–not reached [NR]) vs 22.0 months (95% CI, 21.3-22.7 months) in White patients. Among those with stage II disease, Asian patients had a median OS of 20.4 months (95% CI, 15.0-28.0) compared to 17.5 months (95% CI, 14.8–NR) in Hispanic patients. Again, no significant difference was observed across races (

However, in patients with stage III disease, survival did differ significantly across the races, with a median OS of 12.7 months (95% CI, 12.6-12.9) in White patients vs 13.6 months (95% CI, 13.2-14.1) in African American patients, 13.4 months (95% CI, 10.3-16.9 months) in Hispanic patients, 13.9 months (95% CI, 12.6-15.2 months) in Asian patients, and 13.5 months (95% CI, 11.3-16.7 months) in Native American patients.

“The findings of this cohort study that race is associated with survival of L-SCLC, because Asian and African American patients had better survival compared with White patients,” Kexun Zhou, MBBS, Division of Hematology and Medical Oncology, of Mayo Clinic, and colleagues, wrote. “In addition, our results confirmed that female sex, higher median annual income (≥63,000), private insurance, diagnosis confirmation by positive cytological analysis, larger increase in number of sampled regional lymph nodes examined, and earlier stage at diagnosis were associated with prolonged survival in L-SCLC.”

Along with clinical characteristics and medical care, data have suggested that economic status, medical insurance, sex, and age were linked with occurrence and cancer outcomes. Race has also been considered to be a factor, mostly due to disparities in access to cancer prevention, early detection, and treatment.2,3 Some studies have attributed higher morbidity in African American patients to socioeconomic factors, and others have indicated that race is not an independent predictor of survival when controlling for confounding variables.4-7

Most of these studies were limited by institutional experiences or statewide databases and mainly focused on non–small cell lung cancer and extensive-stage SCLC (ES-SCLC). Because of this, the validity of race, among other factors, for LS-SCLC is not well understood.

For the study, investigators identified patients who had been diagnosed with LS-SCLC between 2004 and 2014. Participants were put into 5 cohorts based on race/ethnicity, as reported by patients in the National Cancer Database. Additionally, residential region was categorized as urban, metro, and rural, and median annual household income was divided into the following categories: less than $38,000, $38,000 to $47,999, $48,000 to $62,999, and $63,000 or more. Moreover, education level was grouped by the percentage of adults with no high school degree in the residential region (less than 7.0%, 7.0% to 12.9%, 13.0% to 20.9%, and 21.0% or greater). Insurance categories included no insurance, government insurance, and private insurance. Diagnostic confirmation was broken up into either histological or cytological analyses, and facility type was classified as non-academic or research program, and academic or research program.

A total of 72,409 patients were included in the analysis. Among these patients, the median age was 67.0 years (range, 23.0-90.0) and just under 60% (55.6%) were women. Moreover, 74.7% were diagnosed with stage III disease, 14.7% had stage I disease, and 10.6% had stage II disease. Regarding racial groups, 90.4% were White, 7.9% were African American, 1.1% were Asian, 0.3% were Hispanic, and 0.3% were Native American.

African American patients were found to have lower income and education levels compared with White and Asian patients. Moreover, African American patients were the largest racial group in the low-income group of less than $38,000 (stage I, 47.1%; stage II, 47.8%; stage III, 50.8%). The same trend was noted in the lower–education level group. Here, African American patients comprised 35.8% of those with stage I disease, 37.2% of those with stage II disease, and 38.7% of those with stage III disease. More than 90% of patients across all races had some form of medical insurance coverage, and the majority had government insurance.

“Eighty-three percent of patients [59,962 patients] were diagnosed according to positive histological findings, and 74% of patients [53,551 patients] were treated at non-academic or research programs across all races,” the study authors wrote. “The exception to this was noted when patients were analyzed by stage, showing that 65% of Hispanic patients [26 patients] with stage I SCLC were treated at academic or research programs. However, the overall number of Hispanic patients remained low.”

Among those with stage I disease, African Americans were found to have lower rates of undergoing surgery for the primary site. No significant differences among races were noted among those with stage II or III disease regarding tumor and treatment characteristics. No difference in the administration of radiation therapy was observed among racial subgroups for any of the disease stages. Although chemotherapy was given to most patients, the proportion was not significantly different among the racial groups except for those with stage II disease. Here, more Hispanic patients received chemotherapy than White, African American, Asian, or Native American patients.

Multivariable analysis revealed that sex, income, education, insurance type, diagnostic confirmation method, number of sampled regional lymph nodes, and disease stage at diagnosis were significantly associated with survival in patients with LS-SCLC. Moreover, African American patients (HR, 0.92; 95% CI, 0.89-0.95; 

 < .001) and Asian patients (HR, 0.83; 95% CI, 0.77-0.91; 

< .001) appeared to be less likely to die from their disease compared with White patients.

Several other factors were found to be associated with longer survival, including female sex (HR, 0.84; 95% CI, 0.83-0.85; 

 < .001), a median annual income of $63,000 or higher (HR, 0.94; 95% CI, 0.90-0.98, 

 < .001), higher education (HR, 0.94; 95% CI, 0.91-0.98, 

= .002), and having private insurance (HR, 0.88; 95% CI, 0.81-0.94, 

 < .001). Patients who had their diagnoses confirmed by positive cytological findings (HR, 0.96; 95% CI, 0.94-0.98; 

 = .003), had an increase in number of sampled regional lymph nodes (HR, 0.99; 95% CI, 0.98-0.99, 

 < .001), and who were diagnosed at an earlier disease stage were all linked with longer survival.

“Given that there is a complex interaction among several factors, more studies are warranted to formulate strategies to overcome the disparities that we have highlighted,” the study authors concluded.

Zhou K, Shi H, Chen R, et al. Association of race, socioeconomic factors, and treatment characteristics with overall survival in patients with limited-stage small cell lung cancer. 

. 2021;4(1):e2032276. doi:10.1001/jamanetworkopen.2020.32276

Ward E, Jemal A, Cokkinides V, et al. Cancer disparities by race/ethnicity and socioeconomic status. 

. 2004;54(2):78-93. doi:10.3322/canjclin.54.2.78

Bach PB, Schrag D, Brawley OW, et al. Survival of blacks and whites after a cancer diagnosis. 

. 2002;287(16):2106-2113. doi:10.1001/jama.287.16.2106

Gadgeel SM, Severson RK, Kau Y, et al. Impact of race in lung cancer: analysis of temporal trends from a surveillance, epidemiology, and end results database. 

. 2001;120(1):55-63. doi:10.1378/chest.120.1.55

Tannenbaum SL, Koru-Sengul T, Zhao W, et al. Survival disparities in non-small cell lung cancer by race, ethnicity, and socioeconomic status. 

. 2014;20(4):237-245. doi:10.1097/PPO.0000000000000058

Videtic GMM, Reddy CA, Chao ST, et al. Gender, race, and survival: a study in non-small-cell lung cancer brain metastases patients utilizing the radiation therapy oncology group recursive partitioning analysis classification. 

. 2009;75(4):1141-1147. doi:10.1016/j.ijrobp.2008.12.022

Kiswas T, Walker P, Podder T, et al. Effect of race and insurance on the outcome of stage I non-small cell lung cancer

“Disparities in Race and Socioeconomic Factors Linked with Outcomes in LS-SCLC”

African American, Asian, and Hispanic patients with limited-stage small cell lung cancer displayed superior survival outcomes compared with White patients, indicating that race might be linked with survival in this disease.

Race, Socioeconomic Factors May Impact Survival Outcome in Limited-Stage Small Cell Lung Cancer 

 demonstrated that men with positive pelvic lymph nodes or a prostatectomy Gleason score of 8 to 10 with disease extending beyond the prostate benefited from adjuvant radiation therapy and that the treatment was associated with a significant reduction of all-cause mortality in this population.

After investigators excluded patients with adverse pathology who had persistent prostate-specific antigen (PSA) expression, the reduced risk of all-cause mortality (ACM) associated with adjuvant radiotherapy remained significant vs early salvage radiation therapy. The association was maintained regardless of whether patients had pelvic nodal involvement (HR, 0.33; 95% CI, 0.13-0.85; 

 = .02) or not (HR, 0.66; 95% CI, 0.44-0.99; 

“We found that among men with adverse pathology at radical prostatectomy including pN1 or prostatectomy Gleason score 8-10 and pT3a or higher PC, adjuvant compared with early salvage radiotherapy was associated with a significant reduction in ACM risk,” the authors of the study wrote. “This association of reduced ACM risk with adjuvant compared with early salvage radiotherapy is strengthened given that men who underwent adjuvant compared with early salvage radiotherapy had less favorable prostate cancer prognostic factor distributions, which should have placed them at higher risk for needing salvage androgen deprivation and dying.”

Patients with prostate cancer who have adverse pathology at radical prostatectomy continue to be at a high risk for recurrence.

 This includes patients with pelvic node–positive disease, prostatectomy Gleason scores of 8 through 10, and extra-prostatic extension or seminal vesicle invasion or invasion into neighboring organs. When this patient population experiences recurrence, their PSA is found to rapidly increase, rising from the trigger PSA level of 0.1 ng/mL or 0.2 ng/mL to 0.4 ng/mL, signifying progression; this can happen while salvage radiotherapy is being planned and delivered, and before PSA response to salvage radiation therapy can be evaluated.

This results in men experiencing progression earlier while on salvage radiotherapy vs adjuvant radiotherapy. Due to this, investigators set out to determine whether those with adverse pathology at radical prostatectomy could derive benefit from adjuvant treatment vs salvage.

The study had a cohort of 26,118 men who had a median age of 62 years (range, 57-67) with pT2-4N0 or N1M0 prostate cancer that had been consecutively treated between June 23, 1989 and July 26, 2016. This treatment needed to include radical prostatectomy and pelvic lymph node assessment, after which patients were followed for possible treatment with adjuvant or early salvage radiotherapy.

The study took place at several institutions, including University Hospital Hamburg-Eppendorf; Charité University Hospital; University Hospital Ulm; University of California, San Francisco; and Johns Hopkins Medical Institution. Patients included in the study were stratified based on the presence or absence of adverse pathology.

Of the patients who were included in the study, 3.14% (n = 819) received adjuvant radiotherapy generally within 6 months of radical prostatectomy and 17.72% (n = 4601) received salvage radiotherapy. The 2 groups had PSA levels of less than 0.1 ng/mL and a median of 0.30 ng/mL, respectively. Among those in the salvage radiotherapy group, 14.24% (n = 655) had persistent PSA levels, defined as a postoperative PSA of 0.1 ng/mL or greater, and were categorized into the early salvage radiotherapy group. Additionally, adjuvant and salvage androgen deprivation therapy were administered in 1.35% and 9.69% of patients, respectively.

After receiving radical prostatectomy to the prostatic bed at a median dose of 68.4 Gy and pelvic lymph nodes (45.0 Gy), adjuvant radiotherapy was delivered a median of 3.55 months. Moreover, adjuvant androgen deprivation therapy was administered for a median of 9.17 months. In total, 5.71% (n = 1491) of the study population had pelvic lymph node–positive disease, of which 21.4% were treated with adjuvant radiotherapy and 16.16% received adjuvant androgen deprivation therapy. Notably, salvage androgen deprivation therapy was administered following PSA failure and clinical or radiographic evidence of progression following adjuvant or salvage radiotherapy.

“Men who received neither adjuvant radiotherapy nor early salvage radiotherapy never experienced PSA failure during the conduct of the study or were treated with salvage androgen deprivation therapy alone at progression,” wrote the authors of the study.

Those with adverse pathology who underwent adjuvant radiotherapy over salvage radiotherapy had a notably higher proportion of pT3a or higher (97.90% and 94.48%, respectively; 

 = .002) and margin-positive disease (82.71% and 45.68%, respectively; 

< .001). Additionally, those who received adjuvant therapy had a significantly higher proportion of patients with margin-positive disease (88.07% and 45.17%; 

< .001) and less use of salvage androgen deprivation therapy (35.78% and 45.84%; 

 = .06) vs early salvage radiotherapy with adverse pathology excluding pN1.

After a median follow-up of 8.16 years (range, 6.00-12.10), investigators reported that 8.06% (n = 2104) of the study population had died, 25.62% (n = 539) of whom passed from prostate cancer. Other findings from the study indicated that there was a significant association identified wherein adjuvant treatment decreased risk of all-cause mortality in men with positive margins (HR, 0.55; 95% CI, 0.34-0.90; 

 = .02) over salvage radiotherapy, although the significance was lost when excluding men with persistent PSA (HR, 0.67; 95% CI, 0.37-1.001; 

 = .0504). No significant association was observed in men without adverse pathology at radical prostatectomy (

Among those with adverse pathology including pN1 who received adjuvant radiotherapy, no radiotherapy, and salvage radiotherapy, investigators reported a 10-year adjusted point estimate for all cause morbidity of 13.78% (95% CI, 8.43%-22.12%), 27.32% (95% CI, 22.54%-32.88%), and 21.98% (95% CI, 18.30%-26.27%), respectively. When excluding pN1, the estimates were 5.13% (95% CI, 2.00%-12.82%), 25.32% (95% CI, 18.95%-33.34%), and 22.15% (95% CI, 17.55%-27.74%), respectively. Moreover, when excluding patients with adverse pathology, the estimates were 7.82% (95% CI, 4.55%-13.28%), 8.81 (95% CI, 7.35%-10.54%), and 7.95% (95% CI, 6.82%-9.24%).

“In conclusion, three randomized trials and a meta-analysis found no difference in progression-free survival for adjuvant compared with early salvage radiotherapy use. However, a benefit might have been missed in men with adverse pathology at radical prostatectomy because of inadequate power and the presence of immortal time bias,” the authors concluded.

Tilki D, Chen Ming-Hui, Wu J, et al. Adjuvant versus early salvage radiation therapy for men at high risk for recurrence following radical prostatectomy for prostate cancer and the risk of death. 

Adjuvant radiation therapy treatment yielded strong results in reducing all-cause mortality in patients with high-risk prostate cancer. 

Hayley Virgil

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