PSMA PET Serosal Uptake Can Look Metastatic Without Being Confirmed on Conventional Imaging
Prostate-specific membrane antigen imaging has changed how recurrent and advanced prostate cancer is staged, restaged, and risk-stratified. It has also made radiologists and clinicians confront a familiar problem in a sharper form: the more sensitive the scan, the easier it becomes to mistake an unusual signal for unequivocal disease. In this correspondence, Daniel Koehler and Tobias Maurer respond to a recent Clinical Outlook on serosal findings seen on PSMA imaging and argue that careful clinical judgment must remain part of image interpretation when the pattern looks ominous but the supporting anatomy does not.
The scenario at the center of the discussion is a patient with recurrent prostate cancer and suspicious uptake along the liver surface on PSMA PET–CT. On fused PET–CT images, the radiotracer accumulations appear multifocal and, at first glance, suggest serosal metastases. Yet the lesions remained stable over time, and conventional imaging did not show corresponding abnormalities. That combination raises an immediate interpretive challenge: the scan appearance can resemble peritoneal or serosal spread, but the broader clinical and radiologic picture may not support that conclusion.
A single scan frame can be persuasive. It can also mislead.
Stable Signal, Absent Correlate, and the Risk of Overcalling Disease
Koehler and Maurer do not dismiss the possibility of malignant spread. Peritoneal carcinomatosis remains a legitimate differential diagnosis in a patient with biochemical recurrence of prostate cancer. Their point is narrower and more clinically practical: not every surface-based focus of tracer uptake should be treated as metastasis without considering alternate explanations. Two possibilities deserve particular attention in this setting — non-prostate cancer-related radiotracer uptake and respiratory motion artefact.
The liver dome and adjacent serosal surfaces are especially vulnerable to misregistration on PET–CT because respiratory motion can shift the apparent position of tracer uptake relative to the anatomic CT data. A lesion that seems to sit on the hepatic capsule may actually reflect movement between the PET acquisition and the CT snapshot. When the uptake pattern remains unchanged and conventional imaging stays negative, the case for artifact strengthens. The correspondence treats this as a reminder that PET signal and true tissue localization are not always identical.
That warning matters because treatment decisions in prostate cancer increasingly track with imaging findings. A false assumption of metastatic serosal disease could push clinicians toward unnecessary escalation, additional invasive workup, or a change in systemic therapy based on a pattern that does not behave like progressive cancer. In a disease where molecular imaging is now central to management, the threshold for calling a lesion malignant has to stay tied to context, not only to visual intensity.
Nonspecific Uptake Is a Known Feature of PSMA Tracers
The authors also place the liver-surface finding within a broader pattern of known PSMA PET pitfalls. Unspecific uptake, especially in bone and particularly in the ribs, is a well-described phenomenon for PSMA tracers. They note that this is especially recognized with [18F]PSMA-1007, but similar nonspecific uptake can occur with other tracers as well, including [18F]DCFPyL, the compound used in the case under discussion.
This point is clinically important because it prevents the reader from anchoring too quickly on one tracer-specific explanation. The problem is not limited to a single radiopharmaceutical. Variability in tracer behavior, biodistribution, and scan interpretation can produce uptake patterns that look pathologic but are not biologically aligned with metastatic tumor deposits. In other words, the scan can be right about tracer localization and wrong about disease meaning.
The correspondence does not provide new outcome data or a comparative study of imaging performance. Its value lies in the interpretive caution it reinforces. When PSMA imaging reveals a suspicious but anatomically unsupported signal, the next step should not be reflexive certainty. Correlation with conventional imaging, temporal evolution, and the possibility of artefact all remain essential.
Why This Matters for Biochemical Recurrence Workups
Biochemical recurrence is one of the most common settings in which PSMA PET is used, and it is also one of the most vulnerable to overinterpretation. Patients in this phase often have rising PSA levels but limited or equivocal anatomic disease. A highly sensitive scan can uncover lesions that were previously invisible, but sensitivity does not erase the need for specificity. The clinical task is to distinguish true metastatic deposits from benign uptake patterns, motion-related misregistration, and other imaging artifacts that can mimic spread.
The liver-surface example is a good test case because it sits at the edge of what PSMA imaging can plausibly explain. Serosal metastases are possible, yet they are not the only explanation for a radiotracer pattern that seems to line the liver surface. If conventional imaging is negative and the appearance stays stable, the burden of proof for calling it metastatic should rise rather than fall. That is especially true when the image is being used to define disease stage, guide salvage treatment, or determine whether a patient has progressed beyond localized recurrence.
Clinical judgment therefore remains a safeguard, not a fallback. Molecular imaging has expanded what clinicians can see, but it has not eliminated ambiguity. The best interpretation still depends on integrating tracer distribution, CT correlation, time course, and the patient’s overall clinical picture.
A Reminder to Read the Scan, Not Just the Hot Spots
The correspondence ultimately argues for restraint in the face of a striking image. Serosal-appearing findings on PSMA PET may represent malignancy, but they may also reflect nonspecific uptake or respiratory motion artefact, particularly when conventional imaging is silent. In that setting, certainty can outrun evidence.
For prostate cancer specialists, the practical message is direct: an abnormal PSMA image should be interpreted with the same discipline applied to any other diagnostic test. When the anatomy does not match the tracer signal, the safer path is correlation, reassessment, and caution — not automatic upstaging based on appearance alone. The remaining challenge is not whether PSMA PET is useful; it clearly is. The challenge is deciding when an ominous image truly means ominous disease.