Improved Imaging for Prostate Cancer With
PSMA PET-CT

Neil Osterweil

March 24, 2020

In men with newly diagnosed high-risk prostate cancer, a new imaging technique was significantly more accurate than the currently used conventional approach in determining the extent of disease, concludes a randomized trial conducted in Australia comparing the two methods.  

A US expert says the novel imaging technique represents a major clinical advance.

"It is absolutely a game-changer for men with prostate cancer," commented Andrei Iagaru, MD, chief of nuclear medicine and molecular imaging at Stanford Health Care in California.

"It has been shown in many studies that it is more sensitive and specific than conventional imaging in the scenario of biochemical recurrence as well as for initial diagnosis and staging prior to surgery," he told Medscape Medical News.

Iagaru was not involved in the Australian study, but he has conducted clinical trials of PET-CT using a different prostate-specific membrane antigen (PSMA) radiotracer than the one used there.

The Australian proPSMA trial was conducted in 300 men with biopsy-proven prostate cancer with high-risk features. The new technique had a 27% greater accuracy than CT and bone scan for diagnosing pelvic nodal or distant metastatic disease, reported Michael S. Hofman, MBBS, from the Peter MacCallum Cancer Center in Melbourne, Australia, and colleagues.

"PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning," they conclude.

The study was published online March 22 in The Lancet.

"Around 1 in 3 prostate cancer patients will experience a disease relapse after surgery or radiotherapy. This is partly because current medical imaging techniques often fail to detect when the cancer has spread, which means some men are not given the additional treatments they need. Our findings suggest PSMA PET-CT could help identify these men sooner, so they get the most appropriate care," said senior author Declan Murphy, MB BCh, director of genitourinary oncology at Peter MacCallum, in a statement.

Details of the proPSMA Trial

Investigators at Peter MacCallum and nine other centers in Australia enrolled men with histopathologically confirmed prostate cancer who were candidates for radical prostatectomy or radiotherapy with curative intent.

These patients all had high-risk features, including at least one of either a PSA concentration of 20 ng/mL or more within 12 weeks before randomization, International Society of Uropathology (ISUP) grade group 3–5, or clinical stage T3 or worse.

Patients were randomly assigned to receive either conventional imaging with CT and bone scan (152 patients), or gallium-68 (68Ga) PSMA-11 PET-CT (148 patients).

Men who had a maximum of two unequivocal distant metastases on first-line imaging were crossed over to have second-line imaging with the alternate technique.

For the primary outcome of accuracy of first-line imaging for identifying pelvic nodal or distant metastases, the investigators found that PSMA PET-CT had 92% accuracy, compared with 65% for CT and bone scanning, an absolute difference of 27% (P < .0001).  Accuracy was defined as the area under the curve (AUC) of receiver operating characteristics using a predefined reference standard that included histopathology, imaging, and biochemistry at 6-month follow-up.

Sensitivity and specificity were also superior with PSMA PET-CT (sensitivity 85% vs. 38%, specificity 98% vs. 91%, respectively).

In subgroup analyses, PSMA PET-CT was also shown to be better at detecting pelvic nodal metastases, with an AUC of 91% vs 59% with CT and bone scanning, and an AUC of 95% vs 74% for distant metastases.

A change in patient management was more common after first-line imaging with PSMA PET-CT than with conventional imaging (28% of men vs 15%, P = .008)

PSMA PET-CT was also associated with less radiation exposure than CT and bone scanning (8.4 mSv vs. 19.2 mSv, respectively, P <.001).

Among patients who had a second-line imaging procedure, patient management was changed in 5% of cases where conventional imaging was the second imaging procedure, compared with 27% of patients who PSMA PET-CT as their second-line imaging.

Kudos and Questions

"Michael Hofman and colleagues should be congratulated for their study," writes Caroline Moore, MD, from the urology department at University College London, UK, in an accompanying editorial.

"The introduction of new imaging modalities, such as PSMA PET-CT, with improved sensitivity in detecting small-volume metastases, brings both challenges and opportunities," she writes. "In particular, when men test negative on conventional imaging, and PSMA PET-CT shows small-volume metastatic disease, what should we do? Hofman and colleagues recognized this challenge and should be commended for explicitly acknowledging on the patient information sheet the uncertainty that arises from novel imaging data, and that the effect of any change in management on long-term outcomes is unknown."

The proPSMA investigators are planning an economic analysis of the potential costs or savings offsets from replacing conventional imaging with
PSMA PET-CT.

Stanford's Iagaru told Medscape Medical News that 68GA-PSMA-11 is not currently approved for use in the United States, adding that a new drug application for the imaging agent has been filed with the US Food and Drug Administration.

The PSMA PET-CT technique, when approved, is likely to be available only in large academic cancer centers initially, but its use will likely expand over time, he predicted.

"I would say that as good as anything is, cancer is a biological process, and we need to look beyond PSMA to cover all aspects of prostate cancer," Iagura said, "but this is definitely a leaping step in imaging high-risk prostate cancer."

The study was funded by the Movember Foundation (a global nonprofit charity dedicated to men's health) and the Prostate Cancer Foundation of Australia. Hofman reported grants from the Prostate Cancer Foundation, the US Department of Defense, and the Victorian Cancer Agency; and personal fees and nonfinancial support from Ipsen, Sanofi Genzyme, and Janssen. Murphy reported personal fees from Astellas, Janssen, Bayer, Ferring, and Ipsen.

Editorialist Moore reported speaker fees from Janssen and Astellas, proctoring fees from Sonablate, and advisory board activity for Steba Biotech and Genomic Health. Iagaru was an investigator in a clinical trial for a PSMA tracer made by Progenics.

The Lancet. Published online March 22, 2020. Abstract, Editorial

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