False positives may occur in 68Ga-PSMA PET-CT imaging for prostate cancer because PSMA expression is also evident in non-prostatic tissue, such as the kidney, gut, breast, brain, adrenal, ovary, salivary gland, celiac ganglion, small intestine, NSCLC, neuroendocrine tumors, Paget’s disease of the bone, and reactive lymph nodes. Despite upregulation of PSMA in prostate cancer secondary to AR inhibition, these other organ sites are important to note. Pitfalls of false positives include the misdiagnosis as metastatic prostate cancer, missing another critical diagnosis, and the inappropriate selection of treatment.
False negatives are not as much of an issue in the overt metastatic disease setting. However, there is a low sensitivity for nodal disease at <4mm, and nodes cannot be detected at <2mm. Furthermore, and importantly, 5-10% of prostate cancers do not express PSMA, and thus one must be aware of PSMA-negative, but FDG-positive patients. The pitfalls of false negatives include radical treatment of incurable patients and unnecessary multimodality treatment of “localized” prostate cancer that is actually metastatic.
A recent prospective single-arm trial assessed the accuracy of 68Ga-PSMA-11 PET in localizing recurrent prostate cancer among 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%).1 The presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients, and detection rates significantly increased with PSA (p<0.001):
- 38% for <0.5 ng/mL (n = 136)
- 57% for 0.5 to <1.0 ng/mL (n = 79)
- 84% for 1.0 to <2.0 ng/mL (n = 89)
- 86% for 2.0 to <5.0 ng/mL (n = 158)
- 97% for ≥5.0 ng/mL (n = 173)
Dr. Davis also highlighted some examples of inappropriate changes in management. For patients with high-risk primary disease, PSMA-detected metastases may lead to the decision to not treat the primary tumor. Second, PSMA imaging may lead to unnecessary additional investigations that delay treatment, such as a rib biopsy for a PSMA avid lesion. Finally, PSMA detected lesions may influence decisions on eligibility of trial participation. An Australian study recently assessed the impact of 68Ga-PSMA PET on management intent among 431 patients with primary or recurrent prostate cancer.2 Before undertaking 68Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing their proposed management plan. A separate follow-up questionnaire was completed after the 68Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change).
Dr. Davis concluded his presentation by highlighting several additional pitfalls:
- Situations exist where PSMA PET is clearly of value, but sometimes there is no added value to the management plan.
- PSMA PET sometimes comes with incomplete information, such as decisions made without treatment context, lack of histology/genomic data, no parallel FDG PET, and a CT component without diagnostic quality.
- PSMA findings may lead to patient distraction, what Dr. Davis notes as “PSMA neurosis.”
Presented by: Ian D. Davis, MBBS, PhD, FRACP, FAChPM, Eastern Health Clinical School, Monash University, Melbourne, Australia
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 2019 Advanced Prostate Cancer Consensus Conference (APCCC) #APCCC19, Aug 29 - 31, 2019 in Basel, Switzerland
Read the Opposing Argument: Advantages of PSM PET-CT in Advanced Prostate Cancer Imaging
- Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol 2019 Jun 1;5(6):856-863.
- Roach PJ, Francis R, Emmett L, et al. The Impact of 68Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study. J Nucl Med 2018 Jan;59(1):82-88.
Further Related Content: Disadvantages in PSMA PET/CT in Advanced Prostate Cancer Imaging Presentation