Just as there are many different types of cancer that exist across patient populations, the independent risk factors impacting cancers vary. As both cancer and hypertension independently impact large patient populations, their association has justified previous research. For example, one nationwide, population-based study found that there was a positive association between hypertension and subsequent urinary bladder cancer, including urothelial carcinoma (Ups J Med Sci 2018; doi: 10.1080/03009734.2018.1473534). Yet, an area that has proven to be understudied is the impact of hypertension on oncologic outcomes in upper tract urothelial carcinoma-specifically with regard to intravesical recurrence after radical nephroureterectomy.
To provide new insight, a team of researchers led by Sohail Dhanji, MD, further explored this topic and the patient impact. Upon completion, he and his team presented their findings at the 2023 American Urological Association Annual Meeting, bringing about new, related questions and the need for subsequent research.
Initially, Dhanji became directly involved in the project due to his role as a research fellow at the University of California at San Diego School of Medicine Department of Urology under the mentorship of Ithaar Derweesh, MD, in March 2022. He credits Derweesh's influence as to what helped make this research possible. Through his instruction, Dhanji explained he was able to learn the skills needed to perform this research and gain access to the information needed to complete this study.
"Our team does a lot of database research, as we are a part of many multi-institutional databases. Initially, we were looking for a link between [body mass index] and outcomes for patients with [upper tract urothelial cancer]," Dhanji shared. "However, hypertension kept standing out as a significant risk factor so we decided to pivot to that as the focus of our research."
Before this study, Dhanji explained that the known impact of hypertension on upper tract urothelial cancer patients undergoing nephroureterectomy was minimal. As a result, he and his team utilized a ROBUUST [ROBotic surgery for Upper tract Urothelial cancer STudy] database. It was formed by merging data collected over time from patients at 20 centers, and then using this data to evaluate the potential relationship between hypertension and upper tract urothelial cancer patients undergoing nephroureterectomy. According to Dhanji, data was pulled from these centers in particular because they were seen as centers of excellence when it comes to urologic oncology.
Using a sample of 865 patients who have received a radical nephroureterectomy in the last 17 years, the researchers followed up with each at a mean interval of 30.5 months to assess several areas of interest. These included overall survival rates, cancer-specific survival rates, and recurrence-free survival (stratified by HTN status). A Kaplan-Meier analysis was also performed to analyze overall outcomes for these rates.
"Kaplan-Meier analysis is [another] effective tool for comparing the survival of different populations," Dhanji said. "A key factor of this analysis is the P value. A P value less than .05 is considered to be indicative of a statistically significant difference between two populations."
To assess the data, patients were divided into groups based on hypertension status. Of the total number of patients observed, 488 had previously been diagnosed with hypertension, leaving 377 free from hypertension symptoms. According to the Mayo Clinic, hypertension is diagnosed when a patient's blood pressure reading is equal to or greater than 130/80 mm Hg, and only after two or more readings have been taken on separate occasions.
Upon the completion of the study, researchers found that the upper tract urothelial cancer patients undergoing nephrectomy and who had been diagnosed with hypertension had a 66.9 percent 3-year overall survival rate. This was compared to the same patient population without hypertension, which was found to have a 79.8 percent 3-year overall survival rate (P=.003).
Further, the 3-year recurrence-free survival rate in the patients without hypertension was 60.6 percent, whereas those with hypertension had a 48.5 percent probability (P=.032). These results contributed to the thinking that hypertension is, in fact, an independent risk factor for worsened upper tract urothelial cancer outcomes for patients undergoing nephroureterectomy. To note, other known risk factors include smoking and chemical exposures. Age and gender have also been hypothesized as risk factors, Dhanji said.
The research additionally showed that, when comparing patients with and without hypertension, there was no significant difference in the percentage of the male gender, mean age, tumor size, or positive margin rate between cohorts. However, patients with hypertension were seen to have higher rates of high tumor grade (78.5% with vs. 69.5% without, P=.005).
Moving forward, Dhanji believes more research must be conducted to solidify the accuracy of these findings and conclusions. If found to be accurate, the need to control hypertension among upper tract urothelial cancer patients could warrant newfound treatment measures. Above all, hypertension remains a condition that patients must closely monitor and seek to consult with their providers regarding.
"At this point, it is hard to say exactly what steps should be taken in terms of hypertension control for this patient population. This is because it has not been determined whether hypertension is a risk factor for developing a worse form of this disease, or whether it leads to worse outcomes after their diagnosis and surgery," Dhanji explained. "However, it is safe to say that these patients should undergo behavioral or pharmacological treatment for hypertension control after obtaining the diagnosis."
He noted that this study could serve as the first step in determining the role of hypertension in upper tract urothelial cancer patients not undergoing nephroureterectomy. Dhanji believes that if his team is able to establish that hypertension, which is present after diagnosis, makes outcomes worse for these patients, then this knowledge "would add a new element to the treatment of UTUC in the form of hypertension control."
In terms of exact questions moving forward, he shared that he and his team have been asked the following:
* What do you think is the exact mechanism for how hypertension affects these patients?
* What do you think the role of renal function was in the survival outcomes for these patients?
"Future research that would need to be conducted would be focused on establishing the exact relationship between hypertension and this disease. As of now, we know that there is a link," Dhanji explained. "The next step would be to characterize this link by showing that hypertension is either a risk factor for developing a worse form of this disease, or whether it makes for worse outcomes once the tumor has formed."
In terms of upper tract urothelial cancer patients not undergoing nephroureterectomy, Dhanji shared that there also exists the possibility that the hypertension risk factor results could remain present. However, he also believes it is entirely possible that hypertension control helps this patient population obtain better outcomes by aiding in the recovery process after surgery. He explained this would have to be investigated independently.
Lindsey Nolen is a contributing writer.