Sylvester Leads in Prostate Cancer Research and Treatment

New trials, drugs and data on racial disparities shed light on one of the most common cancers in men.

While the standard responses to prostate cancer — surgery, radiation, chemotherapy and hormone therapy — have not changed substantially over the years, they have evolved to provide more options when cancer metastasizes and patients are resistant to hormones or chemotherapy. New combinations of traditional medication and genetic testing determine each patient’s best course.

According to the National Institutes of Health (NIH), the 10-year survival rate for localized prostate cancer is around 98%, largely due to early screening. Still, prostate cancer is a leading cause of death for men, particularly men with West African ancestry. For metastatic prostate cancer that has spread to the lungs, bones or liver, five-year survival is around 32% overall, according to the American Cancer Society.

To Treat or Not to Treat

For cancer confined to the prostate, standard care includes prostatectomy and radiation. But both treatments introduce potential side effects, and some men with prostate cancer don’t require treatment for this slow-moving disease.

Treatment decisions depend on the patient’s comorbidities, family history, age, and factors such as genetic profile.

The 1986 Food and Drug Administration (FDA) approval of prostate-specific antigen (PSA) testing contributed to the tripling of prostate cancer diagnoses, said Marijo Bilusic, M.D., Ph.D., medical oncology lead at Sylvester Comprehensive Cancer Center and professor of clinical medicine at the University of Miami Miller School of Medicine, but had little effect on survival rates.

“We treated three times more patients, but a similar number died of prostate cancer,” said Dr. Bilusic.

Historically, metastatic prostate cancer patients who were resistant to hormone therapy and whose disease progressed would escalate to chemotherapy. To be more aggressive in hormone-sensitive disease, said Dr. Bilusic, researchers developed “double therapy,” a combination of docetaxel chemotherapy and androgen-deprivation therapy, or a combination of novel anti-androgens and androgen-deprivation therapy.

“Most recently, we started using triple therapy,” he added, a treatment course consisting of novel anti-androgens (testosterone receptor blockers), chemotherapy and androgen-deprivation therapy that keeps hormone-sensitive patients in remission longer.

A New Way to Treat Tumors

In addition to new treatments, researchers at Sylvester have introduced new drugs to slow the progress of metastatic prostate cancer.

Pluvicto, the brand name for lutetium Lu 177 vipivotide tetraxetan, is a new, radioactive medicine for metastasized hormone-resistant prostate cancer. Matthew C. Abramowitz, M.D., Sylvester radiation oncologist and associate professor at the Miller School, was the principal investigator for a clinical trial at Sylvester.

“This is perhaps the most exciting and sought-after treatment for metastatic prostate cancer that is hormone refractory,” he said.

While Pluvicto is not a cure, it can slow tumor growth and help some men live an average of 18 months longer. An antibody administered through an injection, Pluvicto guides radioactive lutetium to a protein expressed on prostate cancer cells. Once absorbed into the cell, it radiates the cancer.

The drug’s current FDA approval is for metastatic, hormone-resistant and chemo-resistant prostate cancer, and researchers hope study results will move it forward in the treatment course so that it’s offered prior to chemotherapy.

While Dr. Abramowitz emphasizes caution due to the radiation, he said, “Pluvicto provides the opportunity to use radiation to treat cancer throughout the whole body, which is not possible with external beam radiation therapy.”  

New Guidelines, New Questions

Even with new drugs and new therapies, questions remain about whom to treat, how to treat them and the tests involved in diagnosis.

“PSA is important,” said Alan Dal Pra, M.D., director of clinical research, department of radiation oncology at Sylvester, and associate professor of radiation oncology at the Miller School. “But more important is what to do with a PSA result.”

As men age, he said, their prostates enlarge, and they have increased PSA scores.

“A higher PSA,” he said, “doesn’t necessarily mean the patient requires treatment.”

“It used to be that we treated everyone with a high PSA score,” said Sanoj Punnen, M.D., co-chair, Genitourinary Site Disease Group at Sylvester, vice chair of research, Desai Sethi Urology Institute and associate professor at the Miller School. “That has changed quite a bit.”

Urologists, he said, are the strongest advocates for active surveillance.

“MRI is the game-changer in the prognostic space,” said Dr. Punnen.

In the past, he said, an elevated PSA score always led to a biopsy. But today, MRI tests reveal prostate problems and determine whether treatment or surveillance is best.

In a recent trial at Sylvester, Dr. Punnen and his colleagues used MRI to follow a cohort of 200 men with prostate cancer for five years.

“We’re getting a better picture without having to do biopsies every year,” he said.

Today, blood and urinary tests used in concert with MRI determine the need for biopsy. Sylvester researchers, Dr. Punnen said, are also testing artificial intelligence to see if it can identify false positives and false negatives, which can account for up to 20% of MRI results.

Racial Disparities

For several decades, Black men have received less treatment and screening for prostate cancer than other men, according to Brandon Mahal, M.D., assistant director of community outreach and engagement at Sylvester and associate professor at the Miller School.

“Black men are twice as likely to develop it and more than twice as likely to die from it, compared with other men in the U.S.,” he said.

The reasons include genetic factors associated with West African ancestry as well as social determinants of health, including stress, the effects of systemic racism and comorbidities.

“The drivers of increased mortality are in part due to the increased risk of prostate cancer,” Dr. Mahal said, “but also include lack of access to screening and treatment.”

When men with similar disease characteristics are treated similarly, “they tend to have similar outcomes, regardless of race,” said Dr. Mahal.

Sylvester studies found men of African ancestry are more likely to have their cancer progress through more treatments before receiving genomic testing that can help guide management decisions.

“Taken together, we’ve learned that, once diagnosed with advanced disease, differences in genomics are unlikely to drive disparities,” Dr. Mahal said. “Rather, it is more likely differences in care.”

Individualized care, then, is the key for optimal prostate cancer treatment. At Sylvester, “we are truly multidisciplinary,” said Dr. Dal Pra. “We need to give what is best for patients, and that comes to shared decision-making and personalization, talking to patients, and seeing what’s best for each individual.”

Tags: Dr. Alan Dal Pra, Dr. Brandon Mahal, Dr. Marijo Bilusic, Dr. Sanoj Punnen, prostate cancer, Sylvester Comprehensive Cancer Center