Imaging for Prostate Cancer Metastasis Detection - Traditional Imaging (Bone Scan and CT) Versus PSMA-PET-CT, SPECT-CT and Whole-Body MRI

Prostate cancer (PC) is the most common cancer among men. The incidence of PC has increased dramatically in Finland since 1980´s and lately approximately 4.500 new PC cases have been diagnosed annually in Finland.

About one quarter of diagnosed PC are metastatic at the time of diagnosis. Accurate staging is extremely important, as the stage is single most important factor when treatment decisions are made and stage is the single most important prognostic factor. Localized PC is treated with active surveillance (low risk cases), or with treatment modalities with curative intent (radical prostatectomy or radiotherapy).Although recently radical treatments have been suggested to play a role in low volume metastatic disease, the standard treatment of metastatic disease is castration therapy.

In PC staging the most important anatomic locations to be imaged are i) bone, ii) lymph nodes (especially pelvic lymph nodes), and iii) extranodal soft tissues.

Detection of tumor bone metastases is commonly performed by BS. However, the results of recent studies have raised many doubts whether BS is as effective for confirming or excluding metastatic bone disease. Moreover, the sensitivity for 99mTc-methylene diphosphonate bone scintigraphy (99mTc-MDP BS) is only 50-70%. The detection of bone metastases in patients with high-risk PC is significantly improved by SPECT compared to planar BS. Other imaging modalities with potentially improved accuracy to detect bone metastases in PC include PET-scan and whole body MRI.

The value of positron emission tomography (PET) imaging depends on the suitability of used isotope tracer to identify lesions of the imaged tumor type. When bone is imaged with PET, 18F-fluoride has been the most commonly used tracer. Other commonly used PET tracers in PC include 18F-FDG, and 18F/11C-choline, but both have been late more or less replaced by PSMA-PET. Prostate-specific membrane antigen (PSMA) is a trans-membrane protein with an increased expression on cell membranes of PC cells. 68Ga-PSMA HBED-CC (Glu-NH-CO-NH-Lys- (Ahx)-[68Ga(HBED-CC)]) was designed as an extracellular PSMA inhibitor for PET imaging and has been shown to demonstrate high specificity for PSMA-expressing tumor cell. PSMA-PET results have been reported in several studies, but only in three prospective, one including 20-30 patients. Of those studies only study by Fendler and coworkers investigated overall staging, the other two studies by van Leeuwen focused on intraprostatic tumor detection or nodal metastases. Nevertheless, PSMA-PET/CT is a promising imaging modality both for soft tissues and bone. Recently 68Ga-PSMA was reported to outperform 99mTc-DPD-SPECT in detection of bone metastases in PC.