Advanced imaging and emerging biomarkers may help personalize treatment for patients with metastatic prostate cancer by refining disease detection, identifying tumor and immune characteristics, and guiding treatment intensification. Several presentations at the recent 2026 ASTRO Annual Meeting explored the potential of advanced imaging, biomarkers, and immune markers to improve treatment selection and patient outcomes.

Following these presentations, featured expert Amar U. Kishan, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr Kishan on these findings are presented here.

I think that there are several ways we can use advanced imaging and biomarkers together to personalize the treatment of prostate cancer. One clear use of advanced imaging is in the postprostatectomy salvage radiotherapy setting. An example of this scenario would be when a patient has had surgery and then has a rising prostate-specific antigen (PSA) level, and we are considering salvage radiotherapy but we do not know for sure where the rising PSA is coming from. It could be coming from the prostate bed or from somewhere else. This is a clear use case for advanced imaging, which has been studied in several randomized trials.

The phase 2/3 EMPIRE-1 trial compared ¹⁸F-fluciclovine–positron emission tomography/computed tomography (PET/CT) vs conventional imaging and found an event-free survival benefit with ¹⁸F-fluciclovine–PET/CT to help design the radiation field for postprostatectomy salvage radiotherapy. Additionally, the Centre Hospitalier de l’Université de Montréal (CHUM) PSMAiSRT cohort of the phase 2 PSMAgRT trial looked at prostate-specific membrane antigen (PSMA) PET/CT vs conventional imaging and showed a failure-free survival benefit with the PSMA PET/CT–guided intensification of salvage radiotherapy after radical prostatectomy.

At ASTRO 2026, there were several presentations that investigated the role of biomarkers in this space. For example, in the presentation by Shuang Zhao, MD, MSE, we saw that the Prediction Analysis of Microarray 50 (PAM50) genomic classifier might help us identify patients with luminal B–type tumors who could benefit from adding ADT to postprostatectomy salvage radiotherapy (abstract 6). I think that these data represent clear cases of PSMA findings and biomarkers working together. Specifically, advanced imaging can help us refine our radiation fields and targeting, while biomarkers can help inform the use of ADT. We have mature data on both fronts, but they are not necessarily integrated together (ie, the trials and studies evaluating biomarkers have not evaluated advanced imaging, and vice versa).

With regard to radioactive tracer choice, there was a presentation by Jacob Hogan, MD, at ASTRO 2026 that looked at a newer type of PSMA PET/CT radiotracer called flotufolastat F 18 (abstract 1222). This radiotracer could have potential benefit since it is not excreted by the bladder, enabling a better detection of recurrent disease in the prostate bed. Ultimately, in this prospective single-arm study presented by Dr Hogan at the meeting, it was found that even with a very low PSA recurrence following prostatectomy, there is a 49% detection rate of recurrent disease with the flotufolastat F 18 radiotracer.

There are also markers of tumor burden, such as PSMA+ extracellular vesicles. Circulating tumor DNA (ctDNA) or cell-free RNA may be key here. During a session at ASTRO 2026, Praful Ravi, MD, presented data suggesting that a ctDNA fraction of less than 2% may indicate a lower burden of disease and a favorable benefit from ¹⁷⁷Lu-PSMA-617 in the metastatic castration-resistant prostate cancer setting. However, in the oligometastatic setting, high ctDNA levels may identify patients who would actually benefit more from adding ¹⁷⁷Lu-PSMA-617 or another radiopharmaceutical.

I was also very interested in the ArteraAI Prostate Test (Artera, Inc) data presented by Philip Sutera, MD, at ASTRO 2026 (abstract 316). ArteraAI multimodal artificial intelligence (MMAI) is a unique AI biomarker that is a bit of a “black box.” It is not like the Decipher Prostate genomic classifier (Veracyte, Inc), where you know what the genes are. For the study presented at the ASTRO 2026 meeting, investigators looked at a cohort of 187 patients with oligometastatic castration-sensitive prostate cancer and examined the areas that MMAI seemed to flag as concerning. An expert genitourinary pathologist could not differentiate those areas from areas that were not of concern to the biomarker. However, when investigators performed spatial transcriptomics, DNA sequencing, and copy number alteration analyses, they found that the areas that MMAI was detecting seemed to indicate regions of increased epithelial-mesenchymal transition or increased MYC expression and copy numbers. So, MMAI is picking up some biologically aggressive features that may increase metastatic potential.

Also at ASTRO 2026, there was some exciting evidence of a pretreatment immune marker from the feasibility I-STOP study data, which were presented by Patrick Cheung, MD (abstract 109). In this trial, patients with oligometastatic hormone-sensitive prostate cancer identified on PSMA PET/CT were randomized to receive either intermittent ADT or intermittent ADT plus SBRT. In a translational analysis, which looked at the CD14-high vs CD14-low ratio (ie, classical monocytes vs nonclassical monocytes), Dr Cheung and colleagues found that a high ratio (ie, more classical monocytes) predicted better outcomes in patients receiving intermittent ADT plus SBRT. So, this is potentially a predictive biomarker that predicts a benefit to SBRT and not just a prognostic biomarker. It could be that SBRT is releasing the antigens, and being able to harness this baseline increase in classical monocytes would be pretty exciting.

In an educational session at this year’s ASTRO meeting, Zachary Morris, MD, PhD, gave a nice talk explaining that radiation’s immunogenic effect is highly dose dependent. At low doses, you have an increase in T-cell infiltration and favorable modulation; at moderate doses, you have an increase in T-cell killing capacity; and at high doses, you have a more classical increase in macrophages and the release of antigens. Dr Morris really focused on the fact that radiopharmaceutical therapy is very heterogeneous in terms of dose distribution due to nonuniform perfusion variations in the target expression, the composition of the tumor microenvironment, and, possibly, the range of the emitted radiation.

Interestingly, the idea is that this heterogeneity is actually favorable in terms of total immune effect. It was hypothesized by Dr Morris that, when delivering radiopharmaceutical therapy, you can maximize antitumor immunity by using a dose that does not induce severe lymphopenia but maintains immune function by preserving certain regions that get only a low dose and regions that get a high dose. Some good data supporting this hypothesis were presented, including clinical data from patients treated with ¹⁷⁷Lu-PSMA-617, along with data from the phase 2 LUNAR trial.