Janelle Hart

Results of a retrospective study found that Black veterans had a nearly 2-fold greater incidence of prostate cancer (both localized and de novo metastatic disease) compared with White men.

 investigators used data from the Veterans Affairs (VA) national electronic health record in the Corporate Data Warehouse and the VA Central Cancer Registry. All patients in this population had received routine care at VA medical centers across the country between 2005 and 2019 (incidence cohort). Routine care was defined as at least 2 or more clinical encounters, regardless of prostate cancer status.

“The VA provides high-quality care to veterans regardless of race, sex, geographic location, or economic circumstance, thereby creating an equal access system compared to other large health care systems,” Kosj Yamoah, MD, director of Radiation Oncology Cancer Health Disparities Research and section head of Genitourinary Oncology within the Department of Radiation Oncology at Moffitt Cancer Center, Tampa, Florida, said in a news release.

 “This provides us with a unique environment to investigate prostate cancer health disparities across the disease continuum, such as treatment response or overall outcomes at each phase of the disease.”

Of the 7,889,984 Black and White veterans included in this study, 2,788,003 patients underwent prostate-specific antigen (PSA) testing, and 92,269 patients received a diagnosis of prostate cancer between 2005 and 2015 (MO cohort).

After investigators determined the age-adjusted incidence of localized and de novo metastatic prostate cancer, they used multivariable logistic regression to evaluate the relationship between race and ethnicity and pretreatment clinical variables. In addition, they used multivariable Cox proportional hazard models to estimate the risk of metastasis.

The primary outcome was time to distant metastatis after prostate cancer diagnosis. This measured treatment response was compared between Black and White veterans.

According to findings analyzed by the Moffitt Cancer Center, Black men (n=28,802 [31%]) in the MO cohort were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) than White men (n=63,476; [69%]) and had higher PSA levels at the time of diagnosis (>20 ng/mL).

Black men were almost 2 times more likely to be diagnosed with prostate cancer than White men. This remained consistent across VA centers nationwide.

“Increased incidence of prostate cancer is a major driver of the residual disparity in prostate cancer metastasis among African American men. Even in an equal access to care scenario, we saw that adequate, timely therapy is a big factor that will decrease the risk of adverse events, including metastases and death,” Yamoah said.

Results also showed that Black men were 29% more likely to be diagnosed with prostate cancer using a diagnostic prostate biopsy vs White men (hazard ratio, 1.29; 95% CI, 1.27-1.31; 

 <. 001). Although Black men who received treatment for prostate cancer experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; 

 < .001), Black men who were identified as “other” race and received treatment were more likely to develop metastasis (adjusted hazard ratio 1.29; 95% CI, 1.17-1.42; 

Furthermore, a persistent residual metastatic burden for Black men was observed across all National Comprehensive Cancer Network risk groups. In the low-risk group, 4 Black men experienced this burden per 100,000 vs 2 White men. In the intermediate-risk group, 13 vs 6, respectively. In the high-risk cohort, 19 vs 9, respectively.

To the authors’ knowledge, this was the largest study to investigate racial and ethnic disparities across the range of prostate cancer statuses in an equal-access VA setting.

“There is a lot of work still to be done,” Yamoah concluded, “but this data gives us the information we need to develop strategies to combat prostate cancer disparities here in the U.S. and globally.”

1. Yamoah K, Lee KM, Awasthi S, et al. Racial and ethnic disparities in prostate cancer outcomes in the Veterans Affairs health care system. 

 2022;5(1):e2144027. doi:10.1001/jamanetworkopen.2021.44027

2. Moffitt researchers analyze VA data to study prostate cancer disparities. H. Lee Moffitt Cancer Center & Research Institute. January 18, 2022. Accessed January 19, 2022. 

https://www.eurekalert.org/news-releases/940447

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Results also showed that Black men were 29% more likely to be diagnosed with prostate cancer using a diagnostic prostate biopsy vs White men.

Study: Prostate cancer incidence nearly 2-fold higher in Black vs White men

An analysis conducted by Case Western Reserve University and University Hospitals in Cleveland, Ohio showed that the combination of androgen deprivation therapy (ADT) and definitive radiotherapy improves metastasis-free survival among men with localized prostate cancer.

“Our research team set out to conduct a first-of-its-kind, comprehensive analysis by collecting individual patient data from each and every randomized trial conducted around the world, and performed a meta-analysis of the impact of various treatment intensification strategies using hormone therapy with radiation therapy for localized prostate cancer,” said senior author Daniel E. Spratt, MD, in a recent news release.

 “Our goal is to better personalize therapy for prostate cancer patients, by providing the most precise and accurate estimates of the benefit of hormone therapy.”

To gather data, the investigators of this study performed a systematic literature search, in which eligible trials evaluated the use or prolongation of ADT in men with localized prostate cancer who had received radiotherapy. All trials were published in English between January 1, 1962, and December 30, 2020. The search included MEDLINE, Embase, trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), the Web of Science, Scopus, and renowned urology and oncology conference proceedings.

Data were accessed using the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP). Trials were excluded if they did not collect data on distant metastasis or survival, used only non-steroidal anti-androgen therapy (not ADT), took place in a single center, or used lifelong ADT.

The primary outcome of this meta-analysis was metastasis-free survival. HRs for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension, and adjuvant ADT prolongation were produced using Cox models.

After analyzing 12 trials that reflected individual data of 10,853 patients, investigators found that ADT plus radiotherapy (HR 0.83 [95% CI 0.l77-0.89], 

 < .0001) and adjuvant ADT prolongation (0.84 [0.78-0.91], 

 < .0001) both significantly improved metastasis-free survival at a follow up of 11.4 years (IQR 9.0-15.0). However, neoadjuvant ADT extension did not have the same effect (0.95 [0.83-1.09], 

In addition, results showed that there were no significant variations in treatment effects among patients receiving different radiotherapy doses, patients of different ages, or patients of different National Comprehensive Cancer Network risk groups.

“We now have estimates that show the benefit of adding and prolonging adjuvant hormone therapy for clinically relevant subsets of patients,” said Spratt. “Our team showed that treating a group of approximately 10 to 15 men with hormone therapy or extended adjuvant hormone therapy, for at least 18 months, prevented one man from developing metastatic disease 10 years after treatment. This is dependent on patient and tumor specific factors but gives us a more precise estimate to work with when it comes to recommending treatment options.”

“This work from the MARCAP consortium will bring confidence in recommending various treatment intensification strategies, and allow providers to have more accurate, shared-decision making conversations with patients about the benefits of using hormone therapy with radiotherapy for prostate cancer treatment.”

1. Kishan AU, Sun Y, Hartman H, et al. Androgen deprivation therapy use and duration with definitive radiotherapy for localized prostate cancer: An individual patient data meta-analysis. 

2. Researchers show increased survival rate in prostate cancer patients with addition of hormone therapy treatments. News release. University Hospitals Cleveland Medical Center. January 18, 2022. Accessed January 18, 2022. 

https://www.eurekalert.org/news-releases/940306

“Our team showed that treating a group of approximately 10 to 15 men with hormone therapy or extended adjuvant hormone therapy, for at least 18 months, prevented one man from developing metastatic disease 10 years after treatment," says Daniel E. Spratt, MD.

Combination ADT and radiation therapy shows favorable outcomes in men with localized prostate cancer

Overactive bladder continues to be a major issue that negatively impacts the quality of life for urologic patients around the globe. Fortunately, the new drug vibegron (Gemtesa) continues to show promise in clinical trials for treatment of this condition.

Results of the recent phase 3 EMPOWUR extension study

 demonstrated efficacy and safety of vibegron in patients who suffer from overactive bladder, reports 

 Haag-Molkenteller is a chief medical officer at Urovant Sciences, Inc in Irvine, California.

Please discuss the background of the study.

This is another analysis of our EMPOWUR phase 3 study for vibegron , which is an approved treatment for overactive bladder. The first study results were published in 2019. And then we published several sub analyses, including in elderly patients, which is another very important aspect for overactive bladder. This analysis now combined the objective response of the parameters of overactive bladder as micturition frequency, which means how often you go to the bathroom in 24 hours, urge incontinence and urgency, which is one of the leading symptoms, and the patient response to the treatment. The patient voice is very important as well.

What were the findings of this study? And were any of them surprising to you?

First of all, we were very happy with our efficacy and safety results from the EMPOWUR study with the 75 mg of vibegron . This study, of course, showed and confirmed that the patient also perceives the so-called 'objective treatment effect' of their micturition frequency, urgency, [and] urge continence themselves as an improvement, which I think is very important because next to objective parameters, which you gather on the bladder diary, it's also important to hear the patient's voice—how the individual who is being treated feels about the improvement of their symptoms, and feels about the treatment benefit they're receiving. So, this analysis of this publication confirms the link between efficacy and the patient perception, and that the results are actually meaningful to the patients as well.

How will the results of this study impact your company’s clinical development programs for overactive bladder?

I am a chief medical officer of a pharma company. So, we lead the clinical development of drugs. We will always continue to include the patient's voice in our clinical development programs, which means we will have patient-reported outcomes, [or] PROs, in our clinical studies. The individual patient is very important to us at Urovant. So, how the individual patient responds to treatment is very important, and how they feel about the treatment is very important to us as we develop new drugs.

Is there further research on this topic planned? And if so, what will its focus be?

We will continue to read the patient feedback, and we will even focus more on meaningful patient-reported outcomes where the patient can really voice their opinion with the collection of the study results. We will always have, of course, efficacy and safety in a clinical study, but also the patient’s voice and what the treatment means to the patients or individuals. It’s not one group. It’s an individual person. We really strive to approach them as individuals and keep that in mind when we design our clinical studies because we want the patients to really benefit from the treatment and live their life to their fullest.

What is the take-home message for the practicing urologist?

I think for overactive bladder, the practicing urologist will employ the so-called ‘bladder diary.’ They will collect the objective symptoms, which as I said, were micturition frequency, urge incontinence, and urgency in overactive bladder. However, I do believe that all urologists do listen to their patients. It is important to ask the patient how they feel about the treatment. Do they feel that it really helps them? And when they see the results, of course, that is very important. This combination of the objective parameters of the patient's voice and what the treatment means to the patient is extremely important also for a treating urologist or urogynecologist prescribing medications for overactive bladder.

Is there anything else you feel our audience should know about this topic?

As I said before, integrating the patient's voice and what the treatment means to the patient next to objective parameters for any treatment, I think, is extremely important. Patients are human beings, and they're individuals. We need to understand what the treatment [means] to them as individuals, and how they perceive the benefit of the treatment.

1. Staskin D, Frankel J, Varano S, et al. Once-daily vibegron 75 mg for overactive bladder: Long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR)

 2021 May;205(5):1421-1429. Doi: 10.1097/JU0000000000001574. Epub 2020 December 28.

"This analysis of this publication confirms the link between efficacy and the patient perception, and that the results are actually meaningful to the patients as well," says Cornelia Haag-Molkenteller, MD, PhD.

Dr. Haag-Molkenteller on implications of vibegron phase 3 EMPOWUR extension study

In a recent study, investigators found that rising global temperatures will cause significant increases in kidney stone occurrence among Earth’s population.

Results showed that the projected proportion of heat-related kidney stone disease was 0.62% and 0.77% in the 2025-2029 period, vs 2.2% and 3.9% in the 2085-2089 period, for representative concentration pathways (RCPs) 4.5 and 8.5, respectively.

“With climate change, we don’t often talk about the impact on human health, particularly when it comes to children, but a warming planet will have significant effects on human health,” explained senior author Gregory E. Tasian, MD, MSc, MSCE, an attending pediatric urologist in the Division of Urology at Children's Hospital of Philadelphia, in a news release.

 “As pediatric researchers, we have a duty to explore the burden of climate change on human health, as children of today will be living this reality in the future.”

First, to examine the correlation between state-wide daily mean wet-bulb temperatures (WBT) and kidney stone disease presentation in South Carolina, Tasian and co-authors performed an aggregated case-crossover study. The study analyzed data (1997-2014) from the NASA Land Data Assimilation Systems.

An additional study was performed to project the number of heat-related kidney stone disease presentations and associated cost to the year 2089. This was based on the projected daily WBT under 2 different climate change scenarios: RCP 4.5 represented an “intermediate” future with lower greenhouse gas emissions, and RCP 8.5 represented a more extreme future with higher greenhouse gas emissions.

“Our analysis is a model to conceptualize how the burden of kidney stone disease is expected to progress with climate change, and also how mitigations to greenhouse gas emissions can offset some of this burden,” said first author Jason Kaufman, a fourth-year medical student at the University of Pennsylvania Perelman School of Medicine, Philadelphia.

Findings of the first study suggested a mean temperature increase projection of 2.3°C per 5-year period from 2010-2014 to 2085-2089 for RCP 4.5. Conversely, there was a mean temperature increase projection of 3.6°C over the same time frame for RCP 8.5. The number of days projected to exceed the historic maximum daily mean from 1997-2014 (26°C) were also expected to increase over time, especially in RCP 8.5.

Findings of the second study suggested an increase in heat-related kidney stone presentations by 5938 (95% CI 3730-9418) and 10,431 (95% CI 6724-15,581) for RCP 4.5 and 8.5, respectively. There was no evidence of a plateau at higher temperatures. Additionally, the total cost associate with these kidney stone presentations were $56,565,091 and $99,365,184 from 2025-2089 for RCP 4.5 and 8.5, respectively.

Limitations of this study included uncertain association assumptions about temperature and kidney stone presentations and the consideration of only 1 geographic area, among others.

“While it’s impossible to predict with certainty how future policies will slow or hasten greenhouse gas emission and anthropogenic climate change, and to know exactly what future daily temperatures will be, our analysis suggests that a warming planet will likely cause an increased burden of kidney stone disease on health care systems,” concluded Tasian.

1. Kaufman J, Vicedo-Cabrera AM, Tam V, et al. The impact of heat on kidney stone presentations in South Carolina under two climate change scenarios

. 2022;12(1):369 doi:10.1038/s41598-021-04251-2

2. Study shows climate change will lead to increase in kidney stones. News release. Children’s Hospital of Philadhelpia. January 5, 2022. Accessed January 13, 2022. https://www.newswise.com/articles/study-shows-climate-change-will-lead-to-increase-in-kidney-stones?sc=mwhr&xy=10016681

"Our analysis suggests that a warming planet will likely cause an increased burden of kidney stone disease on health care systems,” says Gregory E. Tasian, MD, MSc, MSCE.

Janelle Hart

Articles

Study: Prostate cancer incidence nearly 2-fold higher in Black vs White men

Combination ADT and radiation therapy shows favorable outcomes in men with localized prostate cancer

Dr. Haag-Molkenteller on implications of vibegron phase 3 EMPOWUR extension study

Study finds link between climate change and increases in kidney stone occurrence