PSMA-Avid Serosal Lesions Can Represent Real Metastatic Prostate Cancer
Melissa L. Abel, Esther Mena, Liza Lindenberg, Peter Choyke, and Ravi A. Madan respond to a cautionary discussion about serosal findings on PSMA imaging with a point that shifts the clinical frame. Their central message is straightforward: suspicious-appearing peritoneal or serosal deposits should not be discounted simply because they look unusual or because they seem out of proportion to the rest of the disease burden. The concern is not that these lesions are always benign. The concern is that they may be genuine metastatic prostate cancer with a slow tempo and small-volume distribution that can be easy to undercall on imaging.
This matters because PSMA PET has changed how recurrent prostate cancer is mapped in routine practice. Lesions that once escaped detection can now appear on scan, including sites along the peritoneum, serosa, or hepatic capsule. When the image pattern feels atypical, the reflex response may be to suspect artifact, misregistration, or nonspecific uptake. Yet the correspondence argues against that shortcut, and the published literature they cite supports a more careful interpretation.
A small lesion can be biologically quiet and still be malignant.
Why Peritoneal Uptake Cannot Be Treated as a Simple False Positive
The reply makes a specific distinction. Serosal or peritoneal findings should not be discounted because they are presumed to be false positives. Several histologically confirmed examples of PSMA-avid peritoneal metastases from prostate cancer have already been described, including deposits in the falciform ligament, isolated parietal peritoneal disease, and peritoneal carcinomatosis identified on PSMA PET/CT and PSMA-targeted PET/MR. Those reports are not theoretical edge cases; they show that prostate cancer can seed the peritoneum and retain PSMA expression in these less common metastatic patterns.
The biologic plausibility is important. Prostate cancer metastasis usually announces itself in bone or lymph nodes, but advanced disease does not always follow the most common route. Tumor cells that reach the serosal surfaces may implant in tiny deposits that grow slowly and remain clinically indolent for some time. A low-volume serosal implant can therefore look deceptively minor on imaging while still representing active metastatic disease. In that setting, a scan may be telling the truth even when the pattern appears unfamiliar.
Slow-Growing Disease Can Look Benign on Imaging
The authors also emphasize a practical pitfall: small and slow-growing lesions may be misinterpreted as benign simply because they do not behave like aggressive bulky metastases. In the clinic, that temptation is understandable. Subtle peritoneal nodules are easy to dismiss when the rest of the picture does not fit a widespread metastatic phenotype. But the unusual pattern of serosal or peritoneal involvement, including implants along the liver capsule, has been recognized by multiple groups. Repeated observation across different reports argues against a simple imaging artifact explanation.
That distinction affects treatment planning. If a PSMA-avid serosal lesion is assumed to be benign, the patient may be undertreated. If it is assumed to be a dominant driver of aggressive dissemination without corroboration from the rest of the clinical picture, the patient may be overtreated. The reply lands in the middle: PSMA PET should inform judgment, not replace it. Imaging findings need to be weighed alongside the rest of the disease context, including prior course, tumor burden elsewhere, and the overall tempo of progression.
Clinical Judgment Remains Necessary When Imaging and Biology Diverge
The correspondence supports the broader principle that molecular imaging is a tool for decision-making, not an autonomous verdict. In recurrent prostate cancer, the value of PSMA PET lies in its ability to detect disease that conventional imaging may miss. Its limitation lies in interpretation when the distribution is uncommon. Serosal disease is one of those settings where the scan can be highly informative and still require restraint.
That restraint should not be confused with dismissal. The cited cases include true metastatic deposits confirmed on pathology, which means that an unusual anatomic location does not invalidate the signal. Instead, it raises a more nuanced question: does the lesion represent small-volume, biologically meaningful metastatic spread that warrants clinical attention, even if it is not yet producing dramatic symptoms or widespread radiographic change? For prostate cancer clinicians, that question carries direct implications for staging, surveillance, and therapy selection.
The correspondence also reinforces the value of multidisciplinary interpretation. Nuclear medicine, urology, and oncology teams each see a different part of the picture. A radiologist may recognize an atypical lesion pattern, while the treating oncologist can place it in the context of PSA behavior, prior treatments, and the patient’s broader trajectory. Those perspectives are complementary, and the article argues that none of them should be overridden by imaging alone.
What the Reported Cases Mean for Practice
The literature cited in the reply is small but consequential. It shows that PSMA-positive peritoneal or serosal metastases are rare, yet real enough to merit caution. It also shows that these lesions may present in forms that are subtle, isolated, or misleading on first glance. In a disease where PSMA imaging increasingly shapes management, the lesson is to treat unexpected uptake as a potential metastatic signal until the full clinical context says otherwise.
For clinicians, the practical bedside consequence is clear. When PSMA PET reveals peritoneal, serosal, or hepatic capsular uptake, the answer is not automatic escalation and not automatic dismissal. It is careful correlation with anatomy, disease course, and, when needed, pathology. The possibility of indolent behavior does not make the lesion unimportant; it makes interpretation harder.
This correspondence closes one narrow but important loop in the PSMA imaging debate. Serosal findings should not be presumed false just because they are uncommon. They can represent metastatic prostate cancer, and the imaging pattern alone is not enough to settle the question.
The remaining challenge is operational, not conceptual: deciding when an unusual PSMA-avid lesion deserves tissue confirmation, when it can be followed, and when it should alter treatment in a patient whose other disease features may still appear relatively quiet.