Benjamin Miron, MD, medical oncologist, researcher, Fox Chase Cancer Center, discusses the methods utilized in a study of molecular alterations in patients with intraductal carcinoma of the prostate and the next steps for this research.

At the 2023 ASCO Annual Meeting, Miron and colleagues shared results from this study that examined molecular alterations found in a cohort of patients with intraductal carcinoma of the prostate through an analysis of tissue samples obtained following radical prostatectomy. Investigators then conducted DNA and RNA sequencing to gather additional molecular profiling data to better characterize this histology.

Notably, it was found that the most prevalent alterations in this cohort of patients were 

Investigators evaluated 31 patients, Miron begins, noting that the cohort was small since intraductal carcinoma of the prostate is a relatively new addition to the diagnostic criteria. Investigators are aiming to identify additional cases, he adds. However, in the 31 evaluable patients thus far, 84% had grade group 5 disease, which aligned with what was previously understood about intraductal prostate cancer, Miron explains.

To expand on these initial findings, Miron and colleagues are working closely with a team of pathologists to sort through potential cases and identify more patients via digital pathology slides, Miron says. The goal is to expand this cohort of patients, and once more data regarding the molecular profile of intraductal carcinoma of the prostate are gathered, a comparison could be made against a cohort of patients with prostate adenocarcinoma, he adds. Once this data is obtained, investigators will have a much more robust study, Miron concludes.

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Benjamin Miron, MD, discusses the methods utilized in a study of molecular alterations in patients with intraductal carcinoma of the prostate and the next steps for this research.


Dr Miron on the Methods of Examining Molecular Alterations in Intraductal Carcinoma of the Prostate

Benjamin Miron, MD, medical oncologist, researcher, Fox Chase Cancer Center, discusses the rationale for investigating molecular alterations in patients with intraductal carcinoma of the prostate.

the 2023 ASCO Annual Meeting, Miron and colleagues shared data

 on the results of a study that investigated these molecular alterations. Investigators analyzed tissue samples from patients who underwent radical prostatectomy and conducted DNA and RNA sequencing to gather comprehensive molecular profiling data from the largest cohort of patients with intraductal carcinoma of the prostate reported to date in order to better characterize this histology.

Findings showed that a proportion of patients with intraductal carcinoma of the prostate harbored targetable molecular alterations in mutations such as 

alterations (9.7%). Of the 31 evaluable patients, the most frequently detected alterations were 

Intraductal carcinoma of the prostate was first included in the World Health Organization (WHO) tumor classification in 2016, Miron notes. Moreover, important clinical characteristics of intraductal carcinoma of the prostate include higher volume and more aggressive tumors that are most likely to spread, Miron explains.

Since intraductal carcinoma of the prostate is still a relatively new addition to the WHO classification, this study aimed to provide more data about the molecular profile of this histology and some of the drivers that may differentiate it from other histologies, Miron concludes.

Benjamin Miron, MD, discusses the rationale for investigating molecular alterations in patients with intraductal carcinoma of the prostate.


Dr Miron on the Characteristics of Intraductal Carcinoma of the Prostate

Benjamin Miron, MD, medical oncologist, researcher, Fox Chase Cancer Center, discusses findings and clinical implications from a study investigating molecular alterations in patients with intraductal carcinoma of the prostate.

Dr Miron on the Molecular Landscape of Intraductal Carcinoma of the Prostate

This study evaluated patients with intraductal carcinoma of the prostate who had available tissue-based RNA and DNA sequencing from a commercially available assay. The investigators analyzed these tumor specimens using next-generation sequencing to confirm intraductal histology.

The most prevalent alterations in this cohort of patients with intraductal carcinoma of the prostate were 

 mutations were found in 3.2% of patients, and 

 mutations were found in 3.3% of patients. 

 mutations are actionable and can guide clinical decision making in prostate cancer, as agents such as PARP inhibitors are approved for patients with these mutations, Miron says.

This study also compared the incidence of alterations found in intraductal carcinoma of the prostate with the incidence of alterations found in localized prostate adenocarcinoma and in metastatic castration-sensitive prostate cancer (mCSPC). This analysis found that intraductal carcinoma of the prostate has a genetic landscape that is more similar to metastatic disease than localized disease, Miron explains. For instance, 

 mutations were observed in 38.7% of patients with intraductal carcinoma and 33% of those with mCSPC compared with 3.4% of those with localized disease. 

Dr Miron on Genetic Sequencing in Prostate Cancer

These findings warrant further investigation of the molecular landscape of intraductal carcinoma of the prostate, Miron emphasizes. Comparing the incidence of alterations in this population with that in a population of patients with pure adenocarcinoma of the prostate may reveal additional information about intraductal disease, Miron notes.

For now, however, the actionable mutations found in this study confirm the benefits of early or up-front comprehensive RNA sequencing in patients with intraductal carcinoma of the prostate and support the continued use of germline testing in this population per guideline recommendations, Miron concludes.

Benjamin Miron, MD, discusses findings and clinical implications from a study investigating molecular alterations in patients with intraductal carcinoma of the prostate.

Dr Miron on Molecular Alterations in Intraductal Carcinoma of the Prostate

Benjamin Miron, MD, fellow, Hematology/Oncology, Fox Chase Cancer Center, discusses mechanisms of resistance to FGFR inhibitors in cholangiocarcinoma.

Treatment with FGFR inhibitors can lead to the emergence of several mutations that promote resistance, Miron says. Although there is not much known about these mutations, data from the use of FGFR inhibitors in biliary cancers have shed some light on some resistance mechanisms, Miron explains. These resistance mutations are similar to those that have been observed with other TKIs, such as EGFR inhibitors, Miron adds.

There are currently no approved agents that can target resistance mechanisms to FGFR inhibitors; however, drugs are under development to fill this unmet need, Miron adds. Without approved drugs, the current standard for patients who develop such mutations during treatment with an FGFR inhibitor is to switch therapies or to enroll to a clinical trial, Miron concludes.

Benjamin Miron, MD, discusses mechanisms of resistance to FGFR inhibitors in cholangiocarcinoma.


Dr. Miron on Resistance Mechanisms to FGFR Inhibitors in Cholangiocarcinoma

 It’s hard to think about all the eventualities that could happen. A lot of times, you don’t have multiple opportunities for some patients, so you try to make the best decision that you can. That involves taking the data, which isn’t always based on the exact person in front of you. But sometimes you have to take into consideration the best data that you have and try to fit your patient to that data, both in consideration of the clinical factors that are relevant to the case and what each individual brings of themselves to that decision. Those are overwhelmingly huge factors in what you eventually do, because people have preferences, individual limitations, and wants and needs. That combined with what you know about their case, as far as data points go, help you make that decision.

Some people feel like you have to give your best therapy first. That’s probably what we all want to do, but we still try to stick with the data as best we can because that’s our anchor. As it develops, I’m very open to changing and adapting. It’s important to stay up to date and make those decisions based on growing knowledge. Especially in bladder cancer, there are a lot of data coming in all the time, and that all comes into play. Every person has their own situation, whether it be their medical conditions or who they are, and that all comes together. In bladder cancer, we also look at the toxicities and our patients’ comorbidities to decide on the best choice for that person.

If you’re not an expert on specific disease sites, the top line results are usually the things that come to you and are how you make your decisions. I personally think that most oncologists are motivated to do the best they can and pay attention as much as they can. There’s a lot happening and a lot of new data all the time. I don’t know if I’d necessarily change my practice based on a smaller trial in isolation. Some of that may not be relevant to every oncologist. It’s good to know and stay up to date, but ultimately, the larger studies and registration studies are what usually dictate practice on a larger scale.

People should try to stay up to date as much as they can. In urothelial cancer, there’s going to be much more nuance developing about the options. In treatment after maintenance therapy, there are a lot of considerations that you can think about for what you’d pick next. That may not be something that oncologists have been used to when they’re thinking about bladder cancer, but that will change with time and experience and hopefully with people engaging in case discussions and understanding other people’s perspectives. Maybe that could be a useful thing, too.

There’s a trial that has finished enrolling at Fox Chase Cancer Center [Philadelphia, Pennsylvania] called the RETAIN trial. There’s also RETAIN-2, which is another iteration of a similar concept. That’s really exciting because we always try to cure as many people as we can and maintain their quality of life as best we can. Those studies have that in mind and are trying to optimize—not sacrifice—clinical outcomes and improve quality of life and patient experiences after getting therapy. Those are the things I’m excited about.

We’re also doing a lot of investigations into biomarker work in the perioperative population and developing some trials using biomarkers in the metastatic setting. That’s a personal interest of mine, so I’ll plug that. We’re doing a lot of interesting things in bladder cancer. There’s so much going on in the field in general. I don’t know if I could summarize all of it, but it’s an exciting time. There are a lot more tools in the toolbox. That means that we need to figure out as a group how to best use and sequence them. That’s going to be a good problem to have now that things are developing more.

Dr Benjamin Miron highlights data specific to treating patients with relapsed metastatic disease.

Benjamin Miron, MD

Articles

Dr Miron on the Methods of Examining Molecular Alterations in Intraductal Carcinoma of the Prostate

Dr Miron on the Characteristics of Intraductal Carcinoma of the Prostate

Dr Miron on Molecular Alterations in Intraductal Carcinoma of the Prostate

Dr. Miron on Resistance Mechanisms to FGFR Inhibitors in Cholangiocarcinoma

Encouraging Developments in Therapies for Relapsed/Refractory Advanced Bladder Cancer