Effect of 18F-DCFPyL PET/CT on the Management of Patients with Recurrent Prostate Cancer: Results of a Prospective Multicenter Registry Trial.

Background The high positivity rate of prostate-specific membrane antigen (PSMA) PET in the setting of biochemical failure (BCF), even when conventional imaging is negative, is promising. Purpose To assess the disease detection rate of PSMA-based PET/CT with fluorine 18-DCFPyL as a radiotracer and the PET-directed management change in men with suspected limited recurrent prostate cancer. Materials and Methods This prospective multicenter registry (Ontario PSMA-PET Registry for Recurrent Prostate Cancer, or PREP) enrolled men with BCF after primary therapy (radical prostatectomy plus or minus salvage radiation therapy or primary radiation therapy) and zero to four disease sites at conventional imaging (CT and bone scintigraphy). The positivity rate of PSMA PET according to serum prostate-specific antigen (PSA) level; frequency of local-egional, oligometastatic, and extensive metastatic recurrence; and rate of change in management after PET findings were recorded. The nonparametric Mood median test was used to assess the association between serum PSA level and change in management. Results A total of 1289 men (median age, 71 years [interquartile range, 65-75 years]) were evaluated. PSMA PET helped detect disease in 841 of 1289 men (65%) and in 615 of 999 men (62%) with negative conventional imaging. The recurrence detection rates according to serum PSA level at enrollment were 38% (160 of 424 men), 63% (107 of 171 men), and 83% (573 of 692 men) for PSA under 0.5 ng/mL, 0.5-1.0 ng/mL, and above 1.0 ng/mL, respectively. At PSMA PET, 399 of 1289 men (31%) had local-regional recurrence, 314 (24%) had oligometastatic disease, and 128 (10%) had extensive metastases. Following PET examination, a change in planned management was recorded in 748 of 1289 men (58%), and in 371 of 1250 men (30%), there was a change in management intent, more commonly from palliative to potentially curative intent (255 of 1289 men [20%]). Conclusion Prostate-specific membrane antigen PET helped detect additional sites of disease compared with conventional imaging in approximately 60% of men with biochemical failure and suspected low-volume metastatic disease, resulting in frequent change in management, including a change from palliative to curative or radical intent therapy in 20% of men. Long-term follow-up is needed to determine whether this impacts disease control. Clinical trial registration no. NCT03718260 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Civelek in this issue.

c-MYC overexpression in Ba/F3 cells simultaneously elicits genomic instability and apoptosis.

Overexpression of c-Myc in tumors is usually associated with cell proliferation and increased susceptibility to apoptosis. Concomitantly, c-Myc contributes to tumorigenesis by its ability to destabilize the cellular genome. Here, we examined whether c-Myc induces genomic instability and apoptosis in c-Myc-activated cells. Wild-type Myc (wt-Myc) and two mutated Myc myc box II proteins (mt-Myc) were overexpressed in IL3-dependent murine Ba/F3 cells. As expected, wt-Myc triggered apoptosis in absence of IL3. Standard karyotyping, spectral karyotyping, and fluorescent in situ hybridization (FISH) were performed before and after c-Myc activation. Structural and numerical genomic instability was detected 48 h after wt-Myc activation and included gene amplification, the formation of extrachromosomal elements (EEs), chromosome breakage, deletions, increased aneuploidy, and polyploidization. Interestingly, some cells simultaneously displayed genomic instability and apoptosis. Both wt- and mt-Myc proteins were equally potent promoters of genomic instability. However, only wt-Myc simultaneously induced genomic instability and apoptosis. Mt-Myc proteins failed to induce apoptosis, thereby generating a strong imbalance towards the survival of genomically unstable cells.