Evaluating Biochemically Recurrent Prostate Cancer: Histologic Validation of 18F-DCFPyL PET/CT with Comparison to Multiparametric MRI

Abstract

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) may improve detection of recurrence compared with multiparametric MRI; however, histopathologic validation is lacking. Purpose To determine the sensitivity, specificity, and positive predictive value (PPV) of ¹⁸F-DCFPyL PET/CT based on histologic analysis and to compare with pelvic multiparametric MRI in men with biochemically recurrent prostate cancer. Materials and Methods Men were prospectively recruited after prostatectomy and/or radiation therapy with rising prostate-specific antigen level (median, 2.27 ng/mL; range, 0.2-27.45 ng/mL) and a negative result at conventional imaging (bone scan and/or CT). Participants underwent ¹⁸F-DCFPyL PET/CT imaging and 3.0-T pelvic multiparametric MRI. Statistical analysis included Wald and modified χ² tests. Results A total of 323 lesions were visualized in 77 men by using ¹⁸F-DCFPyL or multiparametric MRI, with imaging detection concordance of 25% (82 of 323) when including all lesions in the MRI field of view and 53% (52 of 99) when only assessing prostate bed lesions. ¹⁸F-DCFPyL depicted more pelvic lymph nodes than did MRI (128 vs 23 nodes). Histologic validation was obtained in 80 locations with sensitivity, specificity, and PPV of 69% (25 of 36; 95% confidence interval [CI]: 51%, 88%), 91% (40 of 44; 95% CI: 74%, 98%), and 86% (25 of 29; 95% CI: 73%, 97%) for ¹⁸F-DCFPyL and 69% (24 of 35; 95% CI: 50%, 86%), 74% (31 of 42; 95% CI: 42%, 89%), and 69% (24 of 35; 95% CI: 50%, 88%) for multiparametric MRI (P = .95, P = .14, and P = .07, respectively). In the prostate bed, sensitivity, specificity, and PPV were 57% (13 of 23; 95% CI: 32%, 81%), 86% (18 of 21; 95% CI: 73%, 100%), and 81% (13 of 16; 95% CI: 59%, 100%) for ¹⁸F-DCFPyL and 83% (19 of 23; 95% CI: 59%, 100%), 52% (11 of 21; 95% CI: 29%, 74%), and 66% (19 of 29; 95% CI: 44%, 86%) for multiparametric MRI (P = .19, P = .02, and P = .17, respectively). The addition of ¹⁸F-DCFPyL to multiparametric MRI improved PPV by 38% overall (P = .02) and by 30% (P = .09) in the prostate bed. Conclusion Findings with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) were histologically validated and demonstrated high specificity and positive predictive value. In the pelvis, ¹⁸F-DCFPyL depicted more lymph nodes and improved positive predictive value and specificity when added to multiparametric MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zukotynski and Rowe in this issue.

Graphical abstract

Figure 1:

Participant flowchart. ¹⁸F-DCFPyL = 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid.

Figure 2a:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 2b:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 2c:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 2d:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 2e:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 2f:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 2g:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–negative, and biopsy-positive lesion in a 65-year-old man (prostate-specific antigen level of 1.85 ng/mL) with history of prostate cancer and prior radical prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL depicted pathologically proven metastatic lesion in right hemipelvis (arrow in [a] PET, [b] PET/CT, and [c] CT) that was missed at multiparametric MRI review due to obscuring susceptibility artifacts from surgical clips at (d) T2-weighted MRI, (e) b = 2000 sec/mm² diffusion-weighted MRI, (f) apparent diffusion coefficient map, and (g) dynamic contrast material–enhanced MRI.

Figure 3a:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–negative, multiparametric MRI–positive, and biopsy-positive lesion in a 67-year-old man (prostate-specific antigen level of 0.42 ng/mL) with history of prostate cancer and prior prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL images ([a] PET and [b] PET/CT) did not show focal findings. (c) Axial T2-weighted MRI, (d) b = 2000 sec/mm² diffusion-weighted MRI, (e) apparent diffusion coefficient map, and (f) dynamic contrast material–enhanced MRI show grade 5 (moderate-high likelihood for recurrent prostate cancer) left-sided focal abnormality at prostatectomy bed, which was biopsy proven as recurrent prostate cancer.

Figure 3b:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–negative, multiparametric MRI–positive, and biopsy-positive lesion in a 67-year-old man (prostate-specific antigen level of 0.42 ng/mL) with history of prostate cancer and prior prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL images ([a] PET and [b] PET/CT) did not show focal findings. (c) Axial T2-weighted MRI, (d) b = 2000 sec/mm² diffusion-weighted MRI, (e) apparent diffusion coefficient map, and (f) dynamic contrast material–enhanced MRI show grade 5 (moderate-high likelihood for recurrent prostate cancer) left-sided focal abnormality at prostatectomy bed, which was biopsy proven as recurrent prostate cancer.

Figure 3c:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–negative, multiparametric MRI–positive, and biopsy-positive lesion in a 67-year-old man (prostate-specific antigen level of 0.42 ng/mL) with history of prostate cancer and prior prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL images ([a] PET and [b] PET/CT) did not show focal findings. (c) Axial T2-weighted MRI, (d) b = 2000 sec/mm² diffusion-weighted MRI, (e) apparent diffusion coefficient map, and (f) dynamic contrast material–enhanced MRI show grade 5 (moderate-high likelihood for recurrent prostate cancer) left-sided focal abnormality at prostatectomy bed, which was biopsy proven as recurrent prostate cancer.

Figure 3d:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–negative, multiparametric MRI–positive, and biopsy-positive lesion in a 67-year-old man (prostate-specific antigen level of 0.42 ng/mL) with history of prostate cancer and prior prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL images ([a] PET and [b] PET/CT) did not show focal findings. (c) Axial T2-weighted MRI, (d) b = 2000 sec/mm² diffusion-weighted MRI, (e) apparent diffusion coefficient map, and (f) dynamic contrast material–enhanced MRI show grade 5 (moderate-high likelihood for recurrent prostate cancer) left-sided focal abnormality at prostatectomy bed, which was biopsy proven as recurrent prostate cancer.

Figure 3e:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–negative, multiparametric MRI–positive, and biopsy-positive lesion in a 67-year-old man (prostate-specific antigen level of 0.42 ng/mL) with history of prostate cancer and prior prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL images ([a] PET and [b] PET/CT) did not show focal findings. (c) Axial T2-weighted MRI, (d) b = 2000 sec/mm² diffusion-weighted MRI, (e) apparent diffusion coefficient map, and (f) dynamic contrast material–enhanced MRI show grade 5 (moderate-high likelihood for recurrent prostate cancer) left-sided focal abnormality at prostatectomy bed, which was biopsy proven as recurrent prostate cancer.

Figure 3f:

Images show 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–negative, multiparametric MRI–positive, and biopsy-positive lesion in a 67-year-old man (prostate-specific antigen level of 0.42 ng/mL) with history of prostate cancer and prior prostatectomy, now with biochemically recurrent prostate cancer. ¹⁸F-DCFPyL images ([a] PET and [b] PET/CT) did not show focal findings. (c) Axial T2-weighted MRI, (d) b = 2000 sec/mm² diffusion-weighted MRI, (e) apparent diffusion coefficient map, and (f) dynamic contrast material–enhanced MRI show grade 5 (moderate-high likelihood for recurrent prostate cancer) left-sided focal abnormality at prostatectomy bed, which was biopsy proven as recurrent prostate cancer.

Figure 4a:

Images show 2-(3-(5)-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–positive, and biopsy-positive lesion in a 62-year-old man (prostate-specific antigen level of 1.48 ng/mL) with history of prostate cancer, treated with external beam radiation therapy, now with biochemically recurrent prostate cancer. Histologically proven lesion in left midbase depicted with ¹⁸F-DCFPyL (arrows) ([a] PET and [b] PET/CT) and multiparametric MRI ([c] T2-weighted MRI, [d] b = 2000 sec/mm² diffusion-weighted MRI, [e] apparent diffusion coefficient map, [f] dynamic contrast material–enhanced MRI) show grade 6 (high likelihood for recurrent prostate cancer).

Figure 4b:

Images show 2-(3-(5)-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–positive, and biopsy-positive lesion in a 62-year-old man (prostate-specific antigen level of 1.48 ng/mL) with history of prostate cancer, treated with external beam radiation therapy, now with biochemically recurrent prostate cancer. Histologically proven lesion in left midbase depicted with ¹⁸F-DCFPyL (arrows) ([a] PET and [b] PET/CT) and multiparametric MRI ([c] T2-weighted MRI, [d] b = 2000 sec/mm² diffusion-weighted MRI, [e] apparent diffusion coefficient map, [f] dynamic contrast material–enhanced MRI) show grade 6 (high likelihood for recurrent prostate cancer).

Figure 4c:

Images show 2-(3-(5)-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–positive, and biopsy-positive lesion in a 62-year-old man (prostate-specific antigen level of 1.48 ng/mL) with history of prostate cancer, treated with external beam radiation therapy, now with biochemically recurrent prostate cancer. Histologically proven lesion in left midbase depicted with ¹⁸F-DCFPyL (arrows) ([a] PET and [b] PET/CT) and multiparametric MRI ([c] T2-weighted MRI, [d] b = 2000 sec/mm² diffusion-weighted MRI, [e] apparent diffusion coefficient map, [f] dynamic contrast material–enhanced MRI) show grade 6 (high likelihood for recurrent prostate cancer).

Figure 4d:

Images show 2-(3-(5)-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–positive, and biopsy-positive lesion in a 62-year-old man (prostate-specific antigen level of 1.48 ng/mL) with history of prostate cancer, treated with external beam radiation therapy, now with biochemically recurrent prostate cancer. Histologically proven lesion in left midbase depicted with ¹⁸F-DCFPyL (arrows) ([a] PET and [b] PET/CT) and multiparametric MRI ([c] T2-weighted MRI, [d] b = 2000 sec/mm² diffusion-weighted MRI, [e] apparent diffusion coefficient map, [f] dynamic contrast material–enhanced MRI) show grade 6 (high likelihood for recurrent prostate cancer).

Figure 4e:

Images show 2-(3-(5)-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–positive, and biopsy-positive lesion in a 62-year-old man (prostate-specific antigen level of 1.48 ng/mL) with history of prostate cancer, treated with external beam radiation therapy, now with biochemically recurrent prostate cancer. Histologically proven lesion in left midbase depicted with ¹⁸F-DCFPyL (arrows) ([a] PET and [b] PET/CT) and multiparametric MRI ([c] T2-weighted MRI, [d] b = 2000 sec/mm² diffusion-weighted MRI, [e] apparent diffusion coefficient map, [f] dynamic contrast material–enhanced MRI) show grade 6 (high likelihood for recurrent prostate cancer).

Figure 4f:

Images show 2-(3-(5)-ureido)-pentanedioic acid (¹⁸F-DCFPyL) PET/CT–positive, multiparametric MRI–positive, and biopsy-positive lesion in a 62-year-old man (prostate-specific antigen level of 1.48 ng/mL) with history of prostate cancer, treated with external beam radiation therapy, now with biochemically recurrent prostate cancer. Histologically proven lesion in left midbase depicted with ¹⁸F-DCFPyL (arrows) ([a] PET and [b] PET/CT) and multiparametric MRI ([c] T2-weighted MRI, [d] b = 2000 sec/mm² diffusion-weighted MRI, [e] apparent diffusion coefficient map, [f] dynamic contrast material–enhanced MRI) show grade 6 (high likelihood for recurrent prostate cancer).