Two Clinical Trials Evaluate Imaging Agent to Detect Prostate Cancer

Cleveland Clinic is participating in two clinical trials evaluating an imaging agent developed specifically to detect prostate cancer cells: rhPSMA-7.3 (18F), a radiohybrid prostate-specific membrane antigen-targeted agent. When used with positron emission tomography (PET), rhPSMA-7.3 (18F) tags prostate-specific membrane antigen (PSMA), a protein on the surface of cancer cells, and identifies it on the scan.

“The exciting thing about PSMA imaging is that it may be able to detect small-volume metastatic cancer cells that are not clearly identified by standard radiotracers not specific to prostate cancer,” says Rahul Tendulkar, MD, a radiation oncologist at Cleveland Clinic Cancer Center. “The goal is to better assess the anatomic extent of the disease before we proceed with treatment. Our ability to tailor treatment to individual patients depends on risk categorization and accurate staging, based on imaging tests that determine the location of the cancer.”

Early findings from a retrospective analysis of 56 patients with intermediate or high-risk prostate cancer found that rhPSMA-7.3 (18F) PET/CT showed a patient-level sensitivity of 81%, specificity of 88% and diagnostic accuracy of 86% when image interpretations were compared to histopathological findings.

“The findings show that rhPSMA-7.3 (18F) is safe, with no major side effects,” says Andrei Purysko, MD, a radiologist in the Department of Diagnostic Radiology at Cleveland Clinic. “Its major advantage over conventional imaging agents is its sensitivity in detecting prostate cancer outside of the prostate in common recurrence sites — the lymph nodes and bones.”

LIGHTHOUSE trial

The LIGHTHOUSE trial is evaluating rhPSMA-7.3 (18F) PET in 375 men newly diagnosed with unfavorable intermediate, high-risk or very high-risk prostate cancer who will be having a radical prostatectomy with pelvic lymph node dissection. The trial will assess the sensitivity and specificity of rhPSMA-7.3 (18F) PET for detecting pelvic lymph node metastases compared to surgical pathology.

“This patient population was chosen because they are at higher risk of having disease outside the prostate, which this agent can identify by attaching to the PSMA receptors,” says Dr. Purysko.

“The purpose of the trial is to see if the scan can identify low-volume lymph node involvement,” adds Dr. Tendulkar. “The gold standard will be pathologic confirmation of results. It would be helpful in planning surgical and other treatments to have this information in advance.”

SPOTLIGHT trial

The SPOTLIGHT trial is evaluating rhPSMA-7.3 (18F) PET in 316 men who have been treated for prostate cancer and have suspected recurrence based on elevated prostate-specific antigen (PSA). The agent will be compared to histopathology or confirmatory imaging.

“The trial may help us learn more about where to target treatment,” says Dr. Tendulkar. “When we treat patients with a rising PSA following surgery, we don’t know the source of this rise, so we deliver treatment based on where we think it is. If we can identify the source, we can shape radiation treatment more carefully, avoid unnecessary treatment and be more aggressive in offering curative treatment to patients who need it.”

Future prospects

These two international multicenter phase 3 trials are currently underway.

“We are very excited to offer this imaging agent to patients and look forward to the results of the trials and hopefully FDA approval in 2021,” says Dr. Purysko. “It has the potential to improve care of patients from the beginning and enable tailored treatment.”

For newly diagnosed patients with more aggressive disease, more precise imaging can determine the extent of the tumor, he says.

“We can escalate treatment based on that. The imaging will highlight affected lymph nodes so we can remove them,” says Dr. Purysko. “For patients with elevated PSA, if the imaging indicates that escalation is limited to the prostate area, they can have less treatment.”

Beyond detection, rhPSMA-7.3 (18F) PET can also enhance treatment. Theranostics — using radioactive agents to both diagnose cancer and deliver treatment — have been used successfully for other cancers. Lutetium lu 177 dotatate (Lutathera®) for neuroendocrine cancers is one example.

“In the future, for patients with very extensive disease that hasn’t responded to conventional treatment, this imaging agent could be used to deliver radiation specifically to the disease site,” says Dr. Purysko. “It could make a huge difference for these patients.”