PSMA PET MRI Spots Prostate Cancer Recurrence in a Quarter of Men Right at the Start of Biochemical Relapse

When prostate-specific antigen begins to climb after radical prostatectomy, urologists face an immediate question: where is the cancer hiding?

To qualify, participants had to have had a PSA below 0.2 ng/ml within the preceding year, ensuring the imaging captured the earliest detectable moment of relapse. Each man underwent an initial 18F-Flotufolastat PSMA PET MRI within two months of signing informed consent. Those whose first scan showed disease were offered salvage treatment; those with a negative scan were monitored with PSA testing at 6 and 12 months and received a second PSMA PET MRI one year after the first, or earlier if their six-month PSA exceeded 0.5 ng/ml.

The imaging itself was performed on a dedicated Biograph mMR scanner capable of acquiring PET and MR images simultaneously. PET data were collected from the top of the skull to the mid-thighs roughly 60 minutes after injection, in 3D mode for two to three minutes per bed position. Multiplanar T1, T2 and diffusion-weighted MR sequences provided attenuation correction and anatomic localization. Board-certified nuclear medicine physicians or radiologists with molecular imaging expertise read every exam, classifying any radiopharmaceutical accumulation higher than surrounding background and not attributable to physiologic uptake as positive for prostate cancer lesions.

The results of the first scan were strikingly granular. Any disease recurrence was identified in 6 of 24 men, or 25 percent. The sites split evenly: two men had recurrence confined to the prostatic bed, two had disease only in pelvic lymph nodes, and two had both the prostatic bed and pelvic lymph nodes involved. All six men with a positive first scan were treated with salvage radiation therapy to the prostatic bed and lymph nodes together with neoadjuvant androgen deprivation therapy, with the specific choice left to the multidisciplinary prostate cancer providers at the institution.

For the 15 men with a negative first scan who had not received salvage treatment, the second scan told a different story. Disease recurrence appeared in 6 of these 15 men, a 40 percent yield at the second time point. Four of the six recurrences were localized to the prostatic bed alone and two to lymph nodes alone. All six were offered salvage radiation therapy with neoadjuvant androgen deprivation therapy, although one man with a prolonged PSA doubling time elected active surveillance instead. Notably, only 4 of the 6 men with a positive second scan had shown a PSA above 0.5 ng/ml, meaning the protocol’s PSA trigger did not catch every eventual scan-positive case.

PSA kinetics offered a suggestive but statistically inconclusive signal. The PSA doubling time among the six men whose second scan showed recurrence was 12.8 months (interquartile range 4.0 to 17.2), compared with 20.8 months (interquartile range 9.1 to 51.7) among the nine whose second scan remained negative, a difference that did not reach statistical significance with p equal to 0.27.

Pooling the protocol-compliant cohort sharpened the picture. Of the 21 subjects who followed the study protocol, PSMA PET MRI identified 14 sites of disease recurrence in 12 subjects within one year of follow-up, a detection rate of 57 percent. Across all studies, recurrence appeared in the prostatic bed in 8 scans and in pelvic lymph nodes in 6. The mean SUVmax values were 4.7 (range 4.3 to 6.0) for prostatic bed lesions and 5.1 (range 3.1 to 7.5) for pelvic lymph node lesions, a difference that was not statistically significant. Three men with a negative first scan who nonetheless received radiation therapy were classified as protocol violations and censored from further follow-up; among the nine non-violation subjects who never showed PSMA PET recurrence on any scan, three were treated with salvage radiation and six remain on active surveillance.

One baseline factor stood out from the rest. PSA prior to radical prostatectomy was significantly higher in men who eventually had demonstrable recurrence on PSMA PET MRI, a median of 9.45 ng/mL (interquartile range 6.74 to 10.4), than in those without localized recurrence, whose median was 4.92 ng/mL (interquartile range 4.37 to 10.4).

The clinical logic behind scanning this early rests on timing. Salvage radiation therapy for recurrence after prostatectomy is most effective when initiated early, and the diagnostic challenge is to determine whether the recurrence is localized to the prostatic bed, lymph nodes, skeleton or solid organs. The authors argue that the 25 percent detection and localization rate at the onset of biochemical recurrence is clinically significant enough to justify obtaining a PSMA PET MRI immediately, and their multidisciplinary group has adopted that practice.

The study’s limitations are candid and substantial. With only 24 enrolled men drawn from a single institution’s longitudinal follow-up program and willing to join a clinical trial, the sample is adequate for estimating detection rates at each imaging time point but not for group comparisons, and the authors describe their recommendations as preliminary. A further general limitation of PSMA PET imaging is that a positive scan may not represent true disease recurrence; biopsying small prostatic bed or lymph node lesions at the onset of biochemical recurrence is technically difficult, and false-negative biopsies can arise from tissue sampling limitations. The investigators assumed positive findings reflected recurrence and treated accordingly.

Subject of Research: Detection rates of 18F-Flotufolastat PSMA PET MRI for localizing prostate cancer recurrence at the onset of biochemical recurrence after radical prostatectomy

Article Title: Detection rate of PSMA PET MRI (18 F-Flotufolastat) at the onset of biochemical recurrence following radical prostatectomy

Article References: Lepor, H., Vargas, H. A., Tafa, M., Wysock, J. S., Tan, W. P., & Nayan, M. (2026). Detection rate of PSMA PET MRI (18 F-Flotufolastat) at the onset of biochemical recurrence following radical prostatectomy. EJNMMI Reports, 10(1), Article 41. https://doi.org/10.1186/s41824-026-00325-4

Image Credits: AI Generated

DOI: 10.1186/s41824-026-00325-4

Keywords: PSMA PET, 18F-Flotufolastat, prostate cancer, biochemical recurrence, radical prostatectomy, PET MRI, salvage radiation therapy, PSA doubling time, prostatic bed recurrence, pelvic lymph nodes, detection rate, oncology imaging