APCCC Diagnostics 2025: False Positive PSMA PET: What to Know?

(UroToday.com) The Advanced Prostate Cancer Consensus Conference (APCCC) Diagnostics 2025, held in Lugano, Switzerland, on February 27^th and 28^th, was host to a session addressing the contemporary management of biochemically recurrent prostate cancer patients. Dr. Irene Burger discussed false positive PSMA PET findings and their implications for clinical practice.

In this presentation, Dr. Burger discussed false positive lesions in the:

• Prostate
• Lymph nodes
• Viscera
• Bone

Starting with false positive lesions in the prostate, Dr. Burger advised that we should be wary of false-positive reads from the transition and central zones, where frequently there will be a high SUV expression that does not necessarily indicate the presence of prostate cancer. We should not ‘fixate’ on SUV parameters but consider as well the location of the uptake in the prostate gland, to minimize false positive reads. Transitional zone lesions that have <2-fold higher uptake, compared to the background, should be considered false positives. Central zone lesions with symmetric uptake (e.g., Mickey Mouse ears) should also be considered false positives. Another important ‘pitfall’ to be wary of is inflammation mimicking a prostate cancer lesion in the peripheral zone.
She emphasized the importance of consistently using the PRIMARY score to grade prostatic lesions, in order to avoid the pitfalls of false positive readings, with this classification system been shown to outperform the MRI-based PIRADS scoring system:¹

• Sensitivity: 88% versus 83%
• Specificity: 64% versus 53%
• Inter-rater reliability: k=0.70 versus 0.58

Next, Dr. Burger discussed false positive nodal lesions. Often, we note uptake in ganglia. To discern false positive from true positives, we need to consider the anatomical location and morphology of these lesions. In the example below, she highlighted tracer uptake in a left sided cervical ganglion that had no morphologic correlate on axial imaging. This is an unlikely position for isolated metastases and the absence of morphologic enlargement on axial imaging is another clue as to the benign nature of this lesion. Additionally, an isolated retro-scapular nodal lesion is also unlikely in this setting (lower right corner).
One scenario to be alert about is the possibility of a 2^nd primary lesion. Any tumor with high neovascularization can be PSMA positive. Common "mimickers" of prostate cancer nodal metastases include:

• Colon cancer
• Renal cell cancer
• Anal cancer
• Bladder cancer
• Neuroendocrine tumors
• Thyroid cancer

The key here is a detailed knowledge of the patient’s clinical history.

With regard to visceral lesions, potential reasons for false-positive findings include hemangiomas, sarcoidosis, and 2^nd primary lesions.

Dr. Burger noted that despite considering anatomy/morphology, it is often difficult to discern true positives from false positives. As such, a biopsy is key in this setting.
What about false positive bone lesions? Benign lesions that may mimic prostate cancer bone metastases include:

• Hemangiomas
• Paget’s disease
• Degenerative disease
• Fibrous dysplasia
• Fractures

One must also consider 2^nd primary lesions, as well as ‘unspecific’ bone lesions.
What about unspecific bone lesions? What do these represent? The most important factor to consider is the tracer used for PSMA PET imaging. False positive bone lesions are significantly more common with ¹⁸F-PSMA-1007 (51.4% of lesions with SUV<10), compared to ⁶⁸Ga-PSMA-11, ⁶⁸Ga-PSMA-I&T, and ¹⁸F-DCFPyL (12-20%).^2,3

As such, Dr. Burger warned that we should have a much higher threshold to biopsy ¹⁸F-PSMA-1007-avid bone lesions. In a series of 11 bone lesions with SUV_max >10 uptake with ¹⁸F-PSMA-1007 PSMA PET, only 1/11 biopsies returned positive for prostate cancer.⁴ For patients with ¹⁸F-PSMA-1007-avid bone lesions, Dr. Burger advised to consider a biopsy only for those patients with PSMA-RADS 5 lesions.

Another important consideration for these unspecified bone lesions is to assess whether there any morphologic correlates, with those having correlates significantly more likely to harbor underlying prostate cancer metastases:
Given the current literature, Dr. Burger’s approach to unspecified bone lesions is as follows:

• For ⁶⁸Ga-PSMA-11, ⁶⁸Ga-PSMA-I&T, and ¹⁸F-DCFPyL avid lesions, consider a biopsy for:
  • PSMA-RADS 4-5 lesions in the staging and biochemically recurrent settings
  • PSMA-RADS 3 in the biochemically recurrent setting, if PSA or Grade Group score is high
• For ¹⁸F-PSMA-1007-avid bone lesions:
  • Consider only for PSMA-RADS 5 

Dr. Burger concluded her presentation with the following ‘advice’ for avoiding false positive PSMA lesions:

1. Prostate:
   1. Consider transition zone lesions as true positives only if the uptake intensity is two-fold higher, compared to the background
   2. Consider central zone lesions as false positives, if the lesion appears symmetric
2. Lymph nodes:
   1. Know the anatomy of ganglia and inflammatory lesions and know the history of 2^nd primaries
3. Viscera:
   1. Know the likelihood of metastatic spread/morphology and biopsy, where appropriate.
4. Bones:
   1. For ⁶⁸Ga-PSMA-11, ⁶⁸Ga-PSMA-I&T, and ¹⁸F-DCFPyL avid unspecified bone uptake, consider a biopsy for:
      1. PSMA-RADS 4-5 lesions in the staging and biochemically recurrent settings
      2. PSMA-RADS 3 in the biochemically recurrent setting, if PSA or Grade Group score is high
   2. For ¹⁸F-PSMA-1007-avid bone lesions:
      1. Consider only for PSMA-RADS 5

Presented by: Irene Burger, MD, Professor, Head of the Department of Nuclear Medicine, Kantonsspital Baden, Baden, Switzerland

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the Advanced Prostate Cancer Consensus Conference (APCCC) Diagnostics 2025 Annual Meeting, Virtual and Lugano, Switzerland, Thurs, Feb 27 – Fri, Feb 28, 2025.

1. Emmett L, Papa N, Buteau J, et al. The PRIMARY Score: Using Intraprostatic ⁶⁸Ga-PSMA PET/CT Patterns to Optimize Prostate Cancer Diagnosis. J Nucl Med. 2022; 63(11): 1644-50.
2. Fendler WP, Eiber M, Beheshti M, et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023; 50(5): 1466-86.
3. Phelps TE, Harmon SA, Mena E, et al. Predicting Outcomes of Indeterminate Bone Lesions on 18F-DCFPyL PSMA PET/CT Scans in the Setting of High-Risk Primary or Recurrent Prostate Cancer. J Nucl Med. 2023; 64(3): 395-401.
4. Ingvar J, Hvittfedlt E, Tragardh E, Simoulis A, Bjartell A. Assessing the accuracy of [18F]PSMA-1007 PET/CT for primary staging of lymph node metastases in intermediate- and high-risk prostate cancer patients. EJNMMI Research. 2022; 12(1):48.