“Our patients are living significantly longer,” said Dorff, associate professor in the Department of Medical Oncology & Therapeutics Research. That’s due in part to “intensified first line therapy,” or better use of existing drugs, as well as a “rapid acceleration” of new drug development. As a result, she says “We can promise men, even with advanced prostate cancer, years of good quality life.”
Good news, considering that prostate cancer is the second most common cancer in men, with over 260,000 new cases every year. And advanced prostate cancer can be deadly, claiming 34,000 lives annually.
Dorff is determined to bring those numbers down. She believes the true path to success is clear.
“Immunotherapy will get us there,” she says.
CAR T Therapy for Solid Tumors
The idea of training the body’s own immune system to fight cancer has percolated throughout the cancer landscape for years now. Dorff is especially excited about the promise of CAR T treatment: taking a patient’s immune, or T cells, reengineering them to recognize specific tumor-associated antigens and then reintroducing them as supercharged cancer killers.
Dorff calls the progress in CAR T therapy “profound and revolutionary.” The Food and Drug Administration has approved two CAR T products for blood cancers.
But solid tumors, including prostate cancer, present special challenges.
Unlike say, leukemia cells, which are fairly uniform, solid tumors are packed with a wide variety of different cells, which means a one-size-fits-all CAR T cell targeting one specific protein can’t mount much of an attack. Also, tumors often display an immunosuppressant microenvironment which can counter the punch of a CAR T onslaught. Finally, there’s the problem of toxicity. Some of the proteins targeted by CAR T cells also exist in healthy tissue.
Dorff is heavily immersed in research and clinical trials to address all these concerns.
“We need to find a way to get the CAR T cells into the tumor with the right amount and find a way to kill tumor cells with different expressions,” she said. “And we need to reduce toxicity and the immunosuppressant response.”
Robotic Surgery: The Beginning of the Future
In their early stages, many prostate cancers can be removed surgically, and here, too, tools are improving rapidly.
Where just a few years ago robotic surgery was a novelty, it is now commonplace. Robotic platforms ― currently in their sixth generation ― keep getting better, and the latest advance ― single port surgery ― may be the most profound to date.
A typical robotic procedure requires up to six small incisions or “ports” for inserting various instruments. The newest da Vinci-brand robotic machine promises to get the same results with just one small incision.
“This is the beginning of the future,” said surgeon Clayton S. Lau, M.D., chief of the Division of Urology and Urologic Oncology and the Pauline & Martin Collins Family Chair in Urology. “It’s still ‘1.0’ but it’s getting better over time.” With fewer incisions, patients could potentially experience less postoperative pain and be able to go home sooner. Lau has already performed some 100 single-port surgeries and reports that some of his patients “can hardly see their scar!”
New Ways to Detect and Destroy Prostate Cancer
Of course, before prostate cancer can be treated, it must first be detected, and the earlier the better. New imaging technology is making a difference here as well.
When prostate cancer is suspected, a biopsy is required to confirm it. A needle guided by an ultrasound machine extracts the tissue sample.
Lau is excited about the magnetic resonance imaging (MRI)-fusion system; using a “parametric” magnetic resonance imaging machine (a special type of MRI that produces a more detailed picture), and grafting those images onto the picture generated by the ultrasound. This method does a much better job pinpointing spots where a biopsy should be taken.
“It gives us a roadmap,” said Lau, “and it decreases the chance of repeated biopsies.”
And what if you could detect AND destroy prostate cancer with the same system?
That’s the promise of a new field called “theranostics.”
“Theranostics is simply a mashup of the words ‘therapeutics’ and ‘diagnostics,’” explained nuclear pharmacist Kofi Poku, Pharm.D. In other words, “You see it; you treat it.”
PSMA: The New Frontier
Doctors routinely use positron emission tomography, or PET, scans to track cancer in the body. A glucose-based radioactive isotope is injected and “lights up” areas where cancer cells ― which need glucose to grow ― exist.
But PET scans can’t see the smallest cells ― less than 1centimeter ― nor can they track cancer cells that haven’t yet begun to ingest glucose.
That’s why a so-called “PSMA-based” PET scan may be a game-changer.
It turns out that more than 80% of all prostate cancer lesions express a prostate-specific membrane antigen, or PSMA. The FDA has approved a pair of drugs ― called “Pylarify” and “Illuccix” ― that recognize those PSMA-positive lesions and bind to them. The drugs are delivered via radioactive isotope, just like the glucose-based version. But now the PET scan “lights up” those areas where PSMA is detected, often finding cells even smaller than anything a conventional PET scan could see.
“With PSMA,” explained Dorff, “we have the ability to find cells even if they’re not metabolically active.”
And once detected, those cells can be zapped by a brand-new drug called Pluvicto, a targeted “radiopharmaceutical” treatment, delivered exactly like the radioisotope deployed to detect the malignant cells in the first place. Pluvicto will hone in on those PSMA-positive lesions and destroy them.
Right now, this PSMA technology is being used primarily on prostate cancer that has spread throughout the body, and the results have been remarkable. Ultimately though, this may become one more critical tool for early detection as well.
“PSMA is the new frontier,” said Dorff, who predicts many other targets will be found and exploited in the coming years. “This is a platform that can be tweaked.” she said.
The “tweaking” has already begun.
“We’re detecting new targets,” said Poku, “and making new drugs to go after them. Over time we’ll have specific (treatments) for many different forms of cancer.”
Bottom line, prostate cancer patients as well as men at risk for the disease have reason to be optimistic now and in the years to come. What’s more, they can improve their chances even further by getting regular screenings to catch even the suspicion of cancer at the earliest possible time.
“When it’s found early,” emphasized Lau, “prostate cancer is very curable, with less aggressive treatment.”