Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33–3.45; p = 0.002; and OR 1.03, 95% CI 1.01–1.04; p < 0.001). Overall upstaging was significantly more frequent among men with GG 5 disease (33.0% vs. 17.6%; p = 0.0097) and PPC ≥50% (33.0% vs 15.0%; p = 0.0020). We constructed a nomogram that predicts overall upstaging using initial prostate-specific antigen, PPC, GG, and cT stage, with coefficients estimated from a standard logistic regression model (using maximum likelihood estimation). It is internally validated with a tenfold cross-validated area under the receiver operating characteristic curve estimated at 0.74 (95% CI 0.67–0.82). In our cohort, 90% of patients who had a nomogram-estimated risk below the cutoff of 22% for overall upstaging could have been spared PSMA PET/CT as our model correctly predicted no upstaging. In other words, the predictive model only missed 10% of patients who would otherwise have benefitted from PSMA PET/CT.
Patient Summary
We analyzed predictors of overall upstaging (lymph node or/and metastasis) by prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) from conventional imaging in men with high-risk prostate cancer undergoing initial staging deemed free of disease in the lymph nodes and distant metastasis by conventional imaging techniques. We found that the pathologic grade and disease burden in a prostate biopsy are associated with upstaging. We also developed a tool that predicts the probability of upstaging according to an individual patient’s characteristics. Our study may help in defining patient groups who are most likely to benefit from the addition of a PSMA PET/CT scan.
Ting Martin Ma1 Andrei Gafita2 David Shabsovich1 Jesus Juarez1 Tristan R.Grogan3 Pan Thin2 Wesley Armstrong2 Ida Sonni2 Kathleen Nguyen2 Vincent Lok2 Robert E. Reiter4 Matthew B. Rettig4,5 Michael L. Steinberg1 Patrick A. Kupelian1 David D. Yang6 Vinayak Muralidhar6 Carissa Chu7 Felix Feng7,8 Ricky Savjani1 Jie Deng1 Neil R. Parikh1 Nicholas G. Nickols1 David Elashoff3 Johannes Czernin2 Jeremie Calais2 Amar U. Kishan1
- Department of Radiation Oncology, UCLA Medical Center, Los Angeles, CA, USA
- Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA Medical Center, Los Angeles, CA, USA
- Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Urology, UCLA Medical Center, Los Angeles, CA, USA
- Department of Medicine, Division of Hematology-Oncology, UCLA Medical Center, Los Angeles, CA, USA
- Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, USA
- Department of Urology, UCSF Medical Center, San Francisco, CA, USA
- Department of Radiation Oncology, UCSF Medical Center, San Francisco, CA, USA
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