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Ruchika Talwar: Hi, everyone. Welcome back to UroToday's Health Policy Center of Excellence. As always, my name is Ruchika Talwar. I'm a urologic oncologist at Vanderbilt in Nashville, Tennessee. Today, I'm joined by Dr. Singla, who is a urologic oncologist at the Brady Institute at Johns Hopkins in Baltimore, Maryland. Dr. Singla is here sharing some of his recent work, looking at testicular cancer outcomes in Hispanic men. Thanks, Dr. Singla, for joining us.

Nirmish Singla: Thank you, Dr. Talwar. And thank you to UroToday also for this wonderful opportunity and platform to share our work. It's really my honor and privilege to share today some of the recent work that we published related to survival outcomes and molecular drivers of testicular cancer in Hispanic men. For reference, here's the citation for the published study that recently came out in urologic oncology. This was a study that was actually jointly led by one of our former urologic oncology SUO fellows, as well as a former medical oncology fellow at Johns Hopkins. I have no relevant disclosures. So as we know it in the United States, the incidence of testicular cancer has been steadily rising. But what's striking about this trend is that the rate of increase has steadily been highest among Hispanics. In fact, there was a study that was published several years ago that even predicted that the incidence of testicular cancer among Hispanics may be the highest by the time 2026 rolls around.

That being said, however, testicular cancer survival is lower in Hispanics compared to non-Hispanic groups, and the underlying reasons for this trend remain unclear. Identifying biological and clinical differences by ethnicity may have an impact on how these patients can be screened and managed after diagnosis in an effort to improve their outcomes. And so the objective of our study was to examine survival outcomes and molecular drivers in testicular cancer by race and ethnicity groups. So this was essentially a two-part study. The first part was more of a clinical aspect of our analysis, and to do this, we leveraged the SEER registry. We looked at a longitudinal registry of patients across 20 years, nearly 44,000 new diagnoses of testicular cancer. We noted that within our cohort, there were nearly one-quarter of patients that were Hispanic. And also specifically noted that when divided among five-year intervals, there was a consistent increase in the trend of new diagnoses of testicular cancer among Hispanic patients. In fact, within the past five years alone, it appears that nearly one-third of patients that were diagnosed with testicular cancer were Hispanic.

At presentation, we noted a few notable findings. First, compared to non-Hispanic white patients, Hispanic patients were more likely to be diagnosed at a younger age. But paradoxically, these patients also seemed to be diagnosed with more aggressive disease characteristics, including more aggressive pathologic characteristics, a greater likelihood of harboring metastatic disease at diagnosis, and also a greater likelihood of having non-seminomatous germ cell tumor histologies as opposed to pure seminoma. We also assessed cancer-specific survival for these groups. We compared this between Hispanics and non-Hispanics as well as other ethnic and racial groups. We also looked at patients based on their histologic composition, either non-seminoma or seminoma, and we looked across different stages as well. We found that within this cohort, cancer-specific survival was significantly lower for Hispanics compared to non-Hispanic whites.

And this was specifically in patients with non-seminoma across all stages. This actually wasn't seen to be the case in seminoma. And on multivariable Cox regression analysis, we also found that this continued to remain statistically significant. As an aside, it was also noteworthy that non-Hispanic black patients also were found to have significantly worse cancer-specific survival compared to their non-Hispanic white counterparts. However, it is also noteworthy that the denominator was much lower for these patients. The second part of this study was an attempt at elucidating the molecular underpinnings behind why this observation was seen clinically. In an effort to do so, we initially turned to publicly available molecularly annotated databases, the most common of which is The Cancer Genome Atlas. Unfortunately, when we looked at the TCGA, there wasn't a sufficient number of self-proclaimed Hispanic patients to make a meaningful analysis. So instead, we turned to the AACR project GENIE dataset. And within this dataset we identified a total of 870 testicular cancer patients, nearly 700 of whom had ethnicity annotation provided.

We divided this cohort based on their histology. So we looked at seminoma and we looked at non-seminoma separately. And we essentially dichotomized the population by Hispanic and non-Hispanic self-proclaimed ethnicities. What we found is that the mutational frequencies were not significantly different between the Hispanic and non-Hispanic groups for both seminoma and non-seminoma. So some of the most common mutations that have been seen in each of these stages, including for example, KIT and KRAS mutations for seminoma and P53 and KRAS mutations in non-seminoma were seen to be prevalent among patients who are self-proclaimed Hispanic ethnicities.

But on a somatic level, there were no significant differences statistically between non-Hispanics and Hispanics. What was noteworthy, however, is that among the patients who self-proclaimed as Hispanic ethnicity, this was a very highly admixed group at an ancestral level. So what we found is that as you can see in the chart on the lower left, for those patients that were Hispanic, it was a very heterogeneous population based on their genetic ancestry. And so this does highlight how difficult it can be to study the biology of this ethnicity. Again, given how heterogeneous this group can be. And this does beg the question further of what other biological assessments can be made to better understand some of the differences that we are seeing on a clinical level.

It's noteworthy to say that there are of course a number of limitations with our study. Indeed, there are many unmeasured factors for each of the race and ethnicity groups highlighted within our study, including, for example, socioeconomic differences, differences with respect to access to care, quality of care rendered, compliance with care protocols, and other unmeasured aspects related to biologic risks that we could not capture with a molecular analysis of somatic mutations alone. But nevertheless, I think it's fair to say that improvement of public awareness would be pertinent to mitigating diagnostic delays in a cancer type that is otherwise very curable. And furthermore, there is a need for better representation of minority groups in future studies, again for a cancer that otherwise exhibits excellent survival.

Ruchika Talwar: Thank you so much. Really interesting study. Very important, obviously, because as you've alluded to, we really don't have a good understanding of why we're seeing this pattern here. And I love that y'all tried to correlate biologic findings potentially with the outcomes that you were seeing in a large national dataset. But in addition to potentially having a push for further diversification of the groups with testicular cancer that we study, in your mind, what are some next steps that we need to move towards as a field to better understand the experience of testicular cancer in Hispanic men?

Nirmish Singla: It's a great question, and I think that as our own awareness as clinicians is continuing to increase, it behooves us to spread that awareness among our populations. And so I think that there are... I would say that actionable areas, maybe they come in two flavors. One, certainly from the standpoint of screening and diagnostic aspects related to testicular cancer in general. There have been a number of studies that have shown that diagnostic delays can be associated with adverse outcomes in testicular cancer. And I think we are seeing that even though again, paradoxically, Hispanic patients are presenting at younger ages, they seem to be harboring more advanced disease at diagnosis. And I think that on the one hand, it may be that we have the ability to reach out to these communities and spread the awareness of the need for testicular cancer screening and seeking care earlier in order to then offer them treatment for their testicular cancer.

And then also as urologists, I think making a push to try and implement guideline-based approaches to screening for testicular cancer, largely because to date, we actually have a USPSTF recommendation. That's a category D recommendation. In the absence of evidence, there isn't sufficient data to support screening across general populations for testicular cancer. And I think that if we can advocate for increasing our level of evidence, there may be an ability to implement routine screening for not just patients, but for general practitioners as well. And then the second sort of actionable aspect would be related to increasing our understanding on a biological level for these patients. And again, we took a cursory look from just simply a high-level view looking at somatic mutations from publicly annotated data sets. But I suspect that there is something on a deeper level that we can understand more mechanistically related to the biology of these tumors that may be different. And this I think is increasing funding for these types of studies. Increasing investigator interest would be a way to really get at this question more deeply.

Ruchika Talwar: Absolutely. I couldn't agree more with all of your points. I think the last thing I'll add is just also understanding that as urologists, we deal with issues that carry a lot of stigma. And in certain cultures particularly, it may be difficult to approach a practitioner or share an issue that's going on potentially related to a finding that someone may have noticed that's suspicious for a testicular mass. So I think really leveling with our patients and encouraging self-exams and seeking care when something abnormal is encountered is important. And particularly outreach in communities that potentially have difficulty with sexual-related topics with discussing abnormal findings on genitalia, et cetera. I think that's really important to stress as well.

Nirmish Singla: Absolutely. I mean, I think in general, I think it's a challenge for testicular cancer, even taking the cultural bit out of it, just because it tends to be a very sensitive topic. Oftentimes it is the most common solid malignancy among males aged 15 to 44. And so this is often an age group that may not expect to even have cancer being so young. But even still noticing something on the testicle, it may not be something that a lot of patients are comfortable sharing with their provider or seeking medical attention or even maybe even aware of from the get-go. So there are a number of factors that can play a role here generally. And then of course, the cultural aspect that you highlighted is very important, I think, to also take into consideration.

Ruchika Talwar: Yeah. Great. Well, thank you for this important work. I think it's a great step in the right direction. As we've reinforced here, we really do need further investigation, understanding what exactly is driving the patterns we're seeing here. But this is a great initial step in at least reporting the experience of Hispanic men with testicular cancer. So thanks for taking the time to chat with us today. We really appreciate it.

Nirmish Singla: Absolutely. And again, thank you so much for this opportunity.

Ruchika Talwar: And to our audience, thanks again for joining. We'll see you next time.