TY - JOUR
T1 - Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer
AU - Xiang, Michael
AU - Ma, Ting Martin
AU - Savjani, Ricky
AU - Pollom, Erqi L.
AU - Karnes, R. Jeffrey
AU - Grogan, Tristan
AU - Wong, Jessica
AU - Motterle, Giovanni
AU - Tosoian, Jeffrey J.
AU - Trock, Bruce J.
AU - Klein, Eric A.
AU - Stish, Bradley J.
AU - Dess, Robert T.
AU - Spratt, Daniel E.
AU - Pilar, Avinash
AU - Reddy, Chandana
AU - Levin-Epstein, Rebecca
AU - Wedde, Trude B.
AU - Lilleby, Wolfgang A.
AU - Fiano, Ryan
AU - Merrick, Gregory S.
AU - Stock, Richard G.
AU - Demanes, D. Jeffrey
AU - Moran, Brian J.
AU - Huland, Hartwig
AU - Tran, Phuoc T.
AU - Martin, Santiago
AU - Martinez-Monge, Rafael
AU - Krauss, Daniel J.
AU - Abu-Isa, Eyad I.
AU - Alam, Ridwan
AU - Schwen, Zeyad
AU - Pisansky, Thomas M.
AU - Choo, C. Richard
AU - Song, Daniel Y.
AU - Greco, Stephen
AU - Deville, Curtiland
AU - McNutt, Todd
AU - Deweese, Theodore L.
AU - Ross, Ashley E.
AU - Ciezki, Jay P.
AU - Boutros, Paul C.
AU - Nickols, Nicholas G.
AU - Bhat, Prashant
AU - Shabsovich, David
AU - Juarez, Jesus E.
AU - Chong, Natalie
AU - Kupelian, Patrick A.
AU - Rettig, Matthew B.
AU - Zaorsky, Nicholas G.
AU - Berlin, Alejandro
AU - Tward, Jonathan D.
AU - Davis, Brian J.
AU - Reiter, Robert E.
AU - Steinberg, Michael L.
AU - Elashoff, David
AU - Horwitz, Eric M.
AU - Tendulkar, Rahul D.
AU - Tilki, Derya
AU - Czernin, Johannes
AU - Gafita, Andrei
AU - Romero, Tahmineh
AU - Calais, Jeremie
AU - Kishan, Amar U.
N1 - Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/12/13
Y1 - 2021/12/13
N2 - IMPORTANCE Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. OBJECTIVES To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing riskstratification tools. DESIGN, SETTING, AND PARTICIPANTS This cohort study included patients diagnosed with highrisk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. EXPOSURES Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. MAIN OUTCOMES AND MEASURES PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. RESULTS Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probabilitywas significantly prognostic of all clinical end points, with 8-year C indicesof 0.63 (95%CI, 0.61-0.65) for BCR, 0.69 (95%CI, 0.66-0.71) for DM, 0.71 (95%CI, 0.67-0.75) for PCSM, and 0.60 (95%CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95%CI, 0.66-0.71] vs STAR-CAP, 0.65 [95%CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95%CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95%CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database.
AB - IMPORTANCE Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. OBJECTIVES To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing riskstratification tools. DESIGN, SETTING, AND PARTICIPANTS This cohort study included patients diagnosed with highrisk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. EXPOSURES Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. MAIN OUTCOMES AND MEASURES PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. RESULTS Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probabilitywas significantly prognostic of all clinical end points, with 8-year C indicesof 0.63 (95%CI, 0.61-0.65) for BCR, 0.69 (95%CI, 0.66-0.71) for DM, 0.71 (95%CI, 0.67-0.75) for PCSM, and 0.60 (95%CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95%CI, 0.66-0.71] vs STAR-CAP, 0.65 [95%CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95%CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95%CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database.
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U2 - 10.1001/jamanetworkopen.2021.38550
DO - 10.1001/jamanetworkopen.2021.38550
M3 - Article
C2 - 34902034
AN - SCOPUS:85121273501
SN - 2574-3805
VL - 4
SP - E2138550
JO - JAMA Network Open
JF - JAMA Network Open
IS - 12
ER -