PSMA PET/CT Validated as Imaging Modality in Prostate Cancer - Medscape

The use of a nomogram derived from prostate-specific membrane antigen (PSMA) PET/CT findings successfully predicted long-term outcomes in patients with high-risk and very high-risk prostate cancer, according to a multicenter study published in JAMA Network Open.

The nomogram was used to estimate the probability of any nonlocalized PSMA-based upstaging and used four variables — initial prostate-specific antigen level, biopsy Gleason grade group, percentage positive cores, and clinical T category — to predict outcomes in 5275 patients from 15 tertiary centers in various countries. The outcomes included distant metastasis, prostate cancer-specific mortality, and overall survival.

The accuracy of the nomogram for correctly identifying nonlocalized disease on PSMA PET/CT imaging was area under the curve (AUC) 0.75 (95% CI, 0.67 - 0.83).

Michael Xiang, MD, PhD, lead author and assistant clinical professor in the Department of Radiation Oncology at the David Geffen School of Medicine, University of California at Los Angeles, noted that the nomogram provides indirect evidence of the power of PSMA PET/CT imaging.

"PSMA PET/CT imaging technology has been revolutionary for the initial workup and staging and even management decisions of prostate cancer," said Xiang in an interview with Medscape Medical News. "We don't yet have long-term data on how initial PSMA PET/CT findings may influence or prognosticate downstream clinical outcomes such as the emergence of distant metastases, death from prostate cancer, or overall survival, which are the most important endpoints."

As it will be several more years before long-term PSMA PET/CT data become available, Xiang sought to use a UCLA-developed nomogram or risk calculator to assess the prognostic validity of PSMA PET/CT data. "No patients in the present study had PSMA PET/CT imaging," said Xiang. "Everything was predicted using the nomogram as a proxy for the predictive result if they were to get PSMA PET/CT (imaging). It was more of an indirect assessment."

The nomogram differs from other risk-stratification tools because it is confined to use in high-risk and very high-risk patients rather than in all-comers, noted Xiang. The nomogram was compared with the Cancer of the Prostate Risk Assessment (CAPRA) groups, the Staging Collaboration for Cancer of the Prostate (STAR-CAP) stage groups, and the Memorial Sloan Kettering Cancer Center (MSKCC) pre-prostatectomy nomogram for 5-year risk of disease progression.

"This proxy for PSMA PET/CT (imaging) is very, very prognostic and outperforms existing risk stratification and prognostic tools for prostate cancer," said Xiang, who noted one exception: performance of the nomogram was similar to STAR-CAP in predicting prostate cancer-specific mortality.

Xiang acknowledged a major limitation of the study: investigators used a proxy rather than actual results of PSMA PET/CT imaging. Another limitation is that the study was conducted retrospectively.

In the future, additional factors such as molecular and genomic data may be used to help predict risk of outcomes in high-risk and very high-risk patients, according to Xiang.

"We would love to incorporate more information such as genomic data and molecular tests," said Xiang. "The combination of our nomogram with genomic data would be even more powerful."

Xiang noted that future directions may involve using the nomogram to help personalize management of patients with high-risk and very high-risk prostate cancer.

"The vision ultimately is that with better prognostic information and risk stratification, we can offer more tailored therapies to patients based on their level of risk," said Xiang. "We can translate these prediction tools into actionable items in the clinic."

Thomas Hope, MD, associate professor in residence, Department of Radiology and Biomedical Imaging, School of Medicine, University of California at San Francisco, noted that Xiang's study demonstrates the utility of this particular nomogram as well as reinforces the use of PSMA PET/CT imaging.

"This work demonstrates the important prognostic value of PSMA PET/CT and really supports the utilization of PSMA PET/CT in high-risk and very high-risk patients and how [the nomogram] has more value than existing nomograms," said Hope in an interview with Medscape Medical News. He was not involved with the study.

Hope noted that the use of the nomogram could potentially offer benefit in countries where PSMA PET/CT imaging is not readily available.

Xiang and Hope have reported no relevant disclosures.

JAMA Netw Open. 2021;4:e2138550. Full text

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