Testicular Cancer Treatment and Cardiovascular Health: Understanding the Long-Term Risks – Khalid Alkhatib

Zach Klaassen: Hi, my name is Zach Klaassen. I’m a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We are live at ASCO 2024, and I’m delighted to be joined by Dr. Khalid Alkhatib, Clinical Research Fellow with Penn Urology. Khalid, thanks so much for joining us today.

Khalid Alkhatib: Well, thank you. It’s my pleasure to come and talk to you this year as well.

Zach Klaassen: That’s great. You joined us last year. We talked about testicular cancer. We’re going to talk about testicular cancer again. You guys have done some great outcomes research looking at cardiovascular toxicity with testicular cancer survivors.

Just by way of background, why are testicular cancer survivors at high risk for cardiovascular disease?

Khalid Alkhatib: To be precise, the exact mechanism is not really well understood, but it is thought that these long-term side effects are somehow related to chemotherapy. There have been lots of proposals and suggestions that chemotherapy does impact the vascular system, which leads to these kinds of manifestations.

Zach Klaassen: Sure.

Khalid Alkhatib: But it’s also important to take into consideration other factors that are also associated with testicular cancer, more specifically metabolic syndrome and hypogonadism. We think that these factors also play a role, but up until now, the exact mechanism that leads to these things is not really well understood.

Zach Klaassen: Yeah, that’s a great answer. Just highlight briefly some of the previous studies that have suggested there are cardiovascular issues with testicular cancer survivors.

Khalid Alkhatib: With regards to survivorship studies, obviously, the Platinum group from the University of Indiana, they started leading the field when they actually, they are one of the first groups that started doing such work, and also other work was done by some of our European colleagues in the Netherlands and Scandinavia. Almost all of these studies were done on exclusive hospital patients, hospital patients seen by the same institutes, but almost all studies agreed that there’s an increased risk of developing strokes by almost six-fold in patients who get treated specifically with Cisplatin.

Also, there’s a higher risk of developing an MI within almost double or three times the risk compared to a normal population. Also, some studies did look at mortality related to cardiovascular events, and also the numbers are really high in comparison to those who never treated with chemo or never had testis cancer.

Zach Klaassen: With that context, what was the objective of your guys’ study that you presented at ASCO this year?

Khalid Alkhatib: The main goal really was to go and see if the numbers from these old studies that were done on a very specific population really reflect what’s there in the public. We wanted to create national datasets and see whether those numbers are also presented on a national level. The biggest problem was really finding testis cancer patients in those national datasets. Usually, numbers are very low and sometimes you don’t have enough power to enable any kind of calculations or any statistics.

But this time we were lucky, to be honest, to find a reasonable number of testis cancer patients in one of the major national datasets by the CDC. We created that dataset for a period of almost 15 years, and we were able to find an adequate number of testis cancer patients.

Zach Klaassen: That’s great.

Khalid Alkhatib: Then we want to compare their results with the national population.

Zach Klaassen: That’s great. Take us through the design and the analysis and some of your key findings that you guys found.

Khalid Alkhatib: Yes. We used a dataset called the Behavioral Risk Factor Surveillance System, which is a survey run by the CDC. It’s an annual survey that is run on the country, and they use a very unique complex weighted design in which the goal is really to study the trends and prevalence of diseases and health behavior at a national level.

What we did is we went back from the year 2004 up until 2022, and we looked at all these national surveys on an annual basis. We created around three million participants and we ended up finding around 300 testis cancer patients. Then we wanted to compare them to healthy males in that national population. Our testis cancer patient cohorts with the median survivorship time of 10 years, and then we did the comparison study using normal descriptive studies, and then we utilized the weight and the study design that is provided by the BRFSS and CDC to go and try to estimate national prevalence.

Zach Klaassen: Right.

Khalid Alkhatib: Then to dig deeper, we also did some extensive modeling, adjusting for different covariates in order to really examine and test the absolute effect of testis cancer in developing these side effects. We used an extensive type of adjustments utilizing the computational utility we have at Penn. We are lucky to work with lots of good data scientists and biostatisticians who helped us to go through all this data.

We came up with estimates and results that really replicate what’s already been reported by previous groups, so that was really the end results of our study.

Zach Klaassen: It’s striking when I looked at your study that for all the metrics, so angina, coronary heart disease, MI, two to four times higher risk than the general population, which is striking. As you said, it corroborates previous studies in Europe and institutions in the US. I guess the $64,000 question is how do we take this data, make it actionable for prostate cancer survivors?

Khalid Alkhatib: I think the data we’re presenting here is really should be the start for taking an action.

Zach Klaassen: Yes.

Khalid Alkhatib: Previously, the criticism of these previous studies that those studies are done on a very specific population, the odds ratios or the risks might be inflated. But this is the first real world national data that really confirms these findings and it’s time to take action, especially when you talk about some of these side effects happening in a period between six or seven to 10 years after survivorship. At this time, we think that it is time to take cardiovascular health as a part of the management of testis cancer survivorship.

Zach Klaassen: Absolutely. I think if you look at a lot of, even at my cancer center, we’re fortunate to have a cardio-oncologist, and I know other centers probably do as well, but I think it’s a point that we talk to these patients. We have a very good chance of curing them of the testis cancer, but it’s a downstream effect. You mentioned 10 years, 20, 30 years. We may not even see them for 20 or 30 years once they’re cured of testis cancer. But it’s important, get them plugged in with primary care doctors. Clearly we need to get them plugged in with cardiologists as well. I think it’s us as the quarterbacks that subsequently need to set this up for these patients.

Khalid Alkhatib: Yes, I think cancer survivorship is really a new domain of medicine. I mean, I come from Penn, so Penn is a little bit unique because we have the first cancer survivorship center in the whole entire world, the whole entire country. They started this back in 20, 25 years ago. But I think cancer survivorship should be a service that is provided in most mainstream health services within the country.

Zach Klaassen: Absolutely.

Khalid Alkhatib: Especially as the survivorship population grows and we see that these long-term adverse effects are serious, and with cardiovascular at least, we think that these effects are most likely or can be preventable and can be really mitigated.

Zach Klaassen: Yeah. Great conversation as always. Leave your listeners with a couple of take-home messages if you could.

Khalid Alkhatib: Take-home messages for us physicians, we need to be vigilant and we need to take our time to communicate to our patients these kinds of risks. Educating patients about the long-term side effects with regards to cardiovascular disease, and also we think that there’s room for us to encourage a cardiovascular healthy lifestyle for our patients. Also mention even minor things like, not minor, even mention important things like smoking cessation, exercise, and healthy diet. Thirdly, is really we need to implement cardiovascular health as part of the management of testis cancer survivorship.

Zach Klaassen: Well said. Always appreciate your time and expertise, Khalid. Thanks so much.

Khalid Alkhatib: Thank you. Thank you so much.

Zach Klaassen: Thanks.