Louise Emmett1, James Buteau2, Nathan Papa3, Daniel Moon4, James Thompson5, Matthew J Roberts6, Kris Rasiah7, David A Pattison6, John Yaxley8, Paul Thomas6, Anthony C Hutton9, Shikha Agrawal10, Amer Amin10, Alexandar Blazevski10, Venu Chalasani7, Bao Ho11, Andrew Nguyen11, Victor Liu11, Jonathan Lee11, Gemma Sheehan-Dare11, Raji Kooner12, Geoff Coughlin8, Lyn Chan11, Thomas Cusick10, Benjamin Namdarian12, Jada Kapoor4, Omar Alghazo4, Henry H Woo13, Nathan Lawrentschuk4, Declan Murphy4, Michael S Hofman2, Phillip Stricker14. 1. Department of Theranostics and Nuclear Medicine, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia; Garvan Institute of Medical Research, Sydney, NSW, Australia. Electronic address: louise.emmett@svha.org.au. 2. Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer, Melbourne, VIC, Australia. 3. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 4. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 5. Department of Urology, St. George Hospital, Kogarah, NSW, Australia; St. Vincent's Prostate Cancer Centre, Darlinghurst, NSW, Australia. 6. Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. 7. Department of Urology, Royal North Shore Hospital, Sydney, NSW, Australia. 8. Wesley Urology Clinic, The Wesley Hospital, Brisbane, QLD, Australia. 9. Department of Urology, St. George Hospital, Kogarah, NSW, Australia. 10. Garvan Institute of Medical Research, Sydney, NSW, Australia. 11. Department of Theranostics and Nuclear Medicine, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia. 12. Department of Urology, St. Vincent's Hospital Sydney, Darlinghurst, NSW, Australia. 13. Sydney Adventist Hospital, Sydney, NSW, Australia. 14. St. Vincent's Prostate Cancer Centre, Darlinghurst, NSW, Australia.
Abstract
BACKGROUND: Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition, 68Ga-PSMA-11 positron emission tomography/computed tomography (prostate-specific membrane antigen [PSMA]) may also identify csPCa accurately. OBJECTIVE: This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa. DESIGN, SETTING, AND PARTICIPANTS: A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy. RESULTS AND LIMITATIONS: Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p < 0.001). Sensitivity also improved (97% vs 83%, p < 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall. CONCLUSIONS: PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging. PATIENT SUMMARY: The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.
BACKGROUND: Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition, 68Ga-PSMA-11 positron emission tomography/computed tomography (prostate-specific membrane antigen [PSMA]) may also identify csPCa accurately. OBJECTIVE: This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa. DESIGN, SETTING, AND PARTICIPANTS: A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy. RESULTS AND LIMITATIONS: Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p < 0.001). Sensitivity also improved (97% vs 83%, p < 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall. CONCLUSIONS: PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging. PATIENT SUMMARY: The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.
Authors: Giancarlo Marra; Taimur T Shah; Daniele D'Agate; Alessandro Marquis; Giorgio Calleris; Luca Lunelli; Claudia Filippini; Marco Oderda; Marco Gatti; Massimo Valerio; Rafael Sanchez-Salas; Alberto Bossi; Juan Gomez-Rivas; Francesca Conte; Desiree Deandreis; Olivier Cussenot; Umberto Ricardi; Paolo Gontero Journal: Front Surg Date: 2022-06-07
Authors: Marnix Rasing; Marieke van Son; Marinus Moerland; Bart de Keizer; Frank Wessels; Trudy Jonges; Sandrine van de Pol; Wietse Eppinga; Juus Noteboom; Jan Lagendijk; Jochem van der Voort van Zijp; Max Peters Journal: Cancers (Basel) Date: 2022-02-03 Impact factor: 6.639