**6. Imaging for prostate cancer**

#### **6.1 MRI imaging**

Magnetic resonance imaging (MRI) is an essential modality for both staging and planning treatment, as it enables enhanced soft tissue resolution over computed tomography (CT). Multi-parametric MRI (mpMRI) includes standard MRI images obtained with at least one additional sequence such as diffusion-weighted imaging (DWI) or dynamic contrast-enhanced (DCE) images in addition to anatomic T2 weighted images. This imaging modality has aided in prostate cancer detection and risk stratification, has been widely used in patients who have a rising PSA with negative biopsies, and in patients who are undergoing active surveillance [12]. Due to its essential role for EBRT treatment, especially for high-dose stereotactic body radiation therapy (SBRT), if a patient is unable to obtain an MRI or his MRI imaging is suboptimal due to issues such as implanted metallic hardware, other treatment modalities such as prostatectomy or brachytherapy may be considered, as appropriate.

### **6.2 PSMA pet/CT**

Several recent clinical trials have demonstrated the diagnostic and therapeutic benefits of prostate-specific membrane antigen (PSMA) in positron emission tomography (PET) imaging. The PSMA peptide is a transmembrane glycoprotein primarily expressed along the extracellular surface of the prostate cancer cell, enabling small molecule binding. The binding site serves as a target for biomarkers for both diagnostic and therapeutic purposes [13]. PSMA demonstrates 100-1000x greater overexpression in prostate adenocarcinoma cells compared to benign prostate tissue, which aids in detecting malignancy [14]. The proPSMA trial demonstrated increased sensitivity with PSMA PET/CT scan in identifying nodal metastatic prostate adenocarcinoma compared to conventional imaging, including the combined findings of CT and bone scans [15].

Both gallium-68 (68 Ga)-PSMA-11 (gozetotide) and fluorine-18 (18 F)-based PSMA compounds are currently widely in use for PET/CT imaging, and PSMA imaging has led to significant changes in clinical management. For example, in the CON-DOR trial investigating the use of 18 F-DCFPy (Pylarify®, piflufolastat) in patients suspected to have a biochemical recurrence after prostatectomy or radiotherapy, among the 208 patients enrolled in the trial, the authors reported a 63.9% rate of change in management [16].

The SPOTLIGHT trial was presented at the American Urological Association Conference, which studied 18F-rhPSMA-7.3 in the biochemical recurrence setting in patients with elevated PSAs. All patients had negative results on conventional imaging, as read by three radiologists; however, on exploratory analysis, this radiotracer led to a 45–47% rate of upstaging [17].
