Dr. Daniel Petrylak

Dr. Daniel P. Petrylak discussed recent developments in prostate cancer care, emphasizing the importance of genetic testing and personalized treatment.

Prostate Cancer Advances in Early Treatment and Emerging Therapies 

Dr. Daniel P. Petrylak, a professor of Medicine (Medical Oncology) and of Urology, as well as the chief of Genitourinary Oncology at Yale School of Medicine in New Haven, Connecticut, shared his insights on recent developments in prostate cancer care and treatment. He emphasized the importance of genetic testing, personalized treatment strategies, and early intervention to improve patient outcomes.

“Currently, only about 40% of patients are being screened for mutations... It should be 100%,” he noted in an interview with CURE.

In the discussion, Petrylak highlighted advances in identifying genetic mutations and emerging strategies for early, intensive treatment for prostate cancer.

What are some recent treatment advancements for prostate cancer that patients should be aware of?

There are a lot of areas of prostate cancer that have really come to the forefront. Firstly, the identification of genetic mutations, particularly the identification of BRCA and the related DNA repair enzymes and deficiencies in those. I think that's important from a therapeutic as well as a familial standpoint. From a familial standpoint, we know that the germline mutations can be passed down from generation to generation. Not only is the patient who has prostate cancer afflicted by that, but the family members can also potentially be afflicted. They need to be properly genetically counseled, including screening for breast cancer, ovarian cancer, and pancreatic cancer, among other cancers that may be involved in these hereditary syndromes.

From a therapeutic standpoint, we're now seeing that DNA repair does play a role as a target for those patients with metastatic prostate cancer. We know that the PARP inhibitors have activity in those BRCA-positive patients. There's a potential synergy between PARP inhibitors and next-generation antiandrogens, as we've seen recently. Moving these agents earlier in the hormone-sensitive state at least shows an improvement in radiographic progression-free survival, and perhaps we will see an overall survival benefit eventually. So, genetics is one theme.

The other theme that dovetails with that is using our agents in metastatic disease earlier. We know that androgen deprivation therapy is the backbone of treatment for metastatic prostate cancer, but adding antiandrogens does show a survival benefit. The question is whether that should be combined with chemotherapy or not, and there's a lot of controversy over which is the right patient to treat in that fashion.

Now, as I mentioned before, the PARP inhibitors are moving up, and the PSMA-targeted agents are moving up. So, intense initial treatment is something that needs to be considered for the appropriate patient in both of those different groups: for the genetic issue, as well as for the early treatment issue.

Currently, only about 40% of patients are being screened for mutations, and about 40 to 50% of patients are receiving intensification up front. It should be 100%—not those low percentage numbers.

Transcript has been edited for clarity and conciseness.

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Videos

Meta: Dr. Daniel P. Petrylak discusses the different types of bladder cancer and how treatment options may vary based on disease stage and type. 

Understanding Unique Treatment Options Across Bladder Cancer Care

Strategies for the treatment of bladder cancer may vary by stage and tumor characteristics, which is important for patients to know, according to Dr. Daniel P. Petrylak, who added that recent advances have offered patients more targeted and effective options across all stages of disease.

To further discuss this topic, Petrylak, chief of Genitourinary Oncology and professor of Medicine (Medical Oncology) and Urology at Yale School of Medicine, located in New Haven, Connecticut, sat down for an interview with CURE during Bladder Cancer Awareness Month.

he explained the different types of bladder cancer

 and how treatment options may vary based on disease stage and type.

There is non-muscle-invasive bladder cancer, muscle-invasive bladder cancer and metastatic bladder cancer. In non-muscle-invasive bladder cancer, treatment depends on the tumor's grade and [any] prior treatments. Low-grade tumors can sometimes be controlled by simply scraping the bladder. However, more aggressive histology may require intravesical therapy, such as BCG, which is a standard of care.

For patients who have [progressed on] BCG, newer agents and standard chemotherapy drugs like gemcitabine and docetaxel can be given inside the bladder to control the disease and prevent it from invading the muscle. The muscle layer is key, and it's crucial to ask your physician whether it's involved and if there was sufficient muscle in the scraping to make that determination, because once the cancer reaches the muscle, the approach changes significantly.

The muscle contains blood vessels and lymphatics that can carry the tumor to other parts of the body. In that situation — cancer in the muscle — we consider bladder cancer to be systemic, similar to breast cancer. Standard chemotherapy, which for years was a combination of drugs called MVAC or gemcitabine and cisplatin, is the standard treatment for these patients before bladder removal.

Discussing the appropriateness of these treatments with the surgeon or oncologist is essential before proceeding with a cystectomy. Afterward, for patients with high-risk disease, we are now using adjuvant immunotherapy. Cystectomy is not the only approach for localized bladder cancer; a combination of chemotherapy and radiation therapy is also an option, and there is ongoing debate about whether this is equivalent to a radical cystectomy. That summarizes localized disease.

In metastatic disease, I think the most significant advances have been made in the last 10 to 15 years. The dawn of immunotherapy in this disease began around 2013 with the first trials of checkpoint inhibitors such as Tecentriq (atezolizumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), Bavencio (avelumab) and Opdivo (nivolumab). Five checkpoint inhibitors were approved at one point and three currently remain as standard treatments. As mentioned, Opdivo is given as adjuvant therapy for a year. There is also data for Keytruda, as well.

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subscribe to CURE®’s newsletters here.

Dr. Daniel P. Petrylak discusses the different types of bladder cancer and how treatment options may vary based on disease stage and type. 

Third-line treatment with Jevtana (cabazitaxel) improved survival among patients with metastatic castration-resistant prostate cancer, according to findings from the CARD trial.

At the European Society of Medical Oncology (ESMO) Congress 2019, 

 spoke with Dr. Daniel Petrylak, professor of medicine and urology at Yale Cancer Center, about these findings and what they mean for the metastatic castration-resistant prostate cancer treatment landscape.

Sequential treatment in prostate cancer is really something that’s evolving over time. We don’t really have an algorithm to help us determine what’s the right drug to use in a given situation.

So, the CARD trial looked at those patients who received docetaxel and at least one second-generation anti-androgen as prior treatment, and they were randomized to receive cabazitaxel or a second-generation anti-androgen such as [Xtandi (enzalutamide)].

And what was found from the study was that there was a better progression-free survival in those patients who received cabazitaxel versus those patients who received the next-generation agent, suggesting that there still is some resistance to the hormonal agents, whether that be through AR-V7 or other mechanisms.

One of the thoughts had been that perhaps, if you treated a patient with chemotherapy such as docetaxel, and they’ve received [Zytiga (abiraterone)] or enzalutamide, that those patients may be re-sensitized in that situation, because of the fact that you can knock out the clones that are AR-V7-positive with docetaxel.

This is actually going against that particular hypothesis and it’s showing that chemotherapy after next-generation androgen docetaxel is the way to go.

Articles

"Sequential treatment in prostate cancer is really something that’s evolving over time," Dr. Daniel Petrylak said of the study findings presented at the European Society of Medical Oncology Congress 2019.

Dr. Daniel Petrylak

Prostate Cancer Advances in Early Treatment and Emerging Therapies

Understanding Unique Treatment Options Across Bladder Cancer Care

Third-Line Jevtana Improves Progression-Free Survival in Prostate Cancer Subtype

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