PSMA PET: A 'Real Game Changer' in High-Risk Prostate Cancer

Susan London

November 18, 2020

Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.

"PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis," noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.

The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.

"These findings carry significant clinical implications and can affect treatment decision-making," Ma noted.

With the current study, Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.

The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scans were excluded.

Study Results

PSMA PET/CT led to nodal upstaging — from N0 to N1 — in 19.7% of patients and metastasis upstaging — from M0 to M1a, b, or c — in 9.4%.

"It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study," Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.

In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio [OR] per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).

Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).

Other factors — clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features — did not independently predict these outcomes.

When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs 5.9% among all others).

"Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan," Ma concluded. "Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.

"The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy," he added. "It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent-positive cores into clinical risk stratification schemes for clinical use."

A Game Changer

"PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics," said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, Australia, who was not involved in this study.

"PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy," Eapen added.

Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a "one-stop-shop" scan.

"This prospective study by Ma et al is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT," Eapen said. "As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit."

The study did not receive any specific funding. Ma and Eapen have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting: Abstract 58. Presented October 25, 2020.

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