Oligometastatic PCa: Smarter selection, better outcomes

The first lecture was ‘The biology of oligometastatic disease’ by Prof. Phuoc Tran (US). He stated that oligometastatic clinical manifestations-phenotypes are determined by an underlying attenuated pro-metastatic biology. “This is reflected reasonably well by enumeration of metastases, but likely better at the DNA, RNA protein and tumour microenvironment level.”

He emphasised, “A deeper understanding of metastatic biology can better instruct the rationale design of combined systemic and local therapy for metastatic disease, from established treatments to the nomination of novel therapies.”

Prof. Betrand Tombal (BE) presented “The road to cure: Does intensification matter?” where he examined the evolution of treatment options based on the use of conventional imaging and modern imaging. “Patients with oligo-progressive on conventional imaging typically have low-volume asynchronous PCa, thus ADT + APRI is the standard of care. They are also likely to be multi-metastatic on conventional imaging, which makes them poor candidates for metastasis-directed therapies (MDT).”

According to Prof. Tombal, patients diagnosed with oligo-progressive on modern imaging often still pertain to the historical BCR stage. Systemic intensification should be guided by the intrinsic risk of progression, and there is limited benefit of ADT alone. Low-risk BCR (with or without olioM+ on new imaging) should not receive systemic treatment. Enzalutamide (and most likely other APRIs) significantly improve metastatic-free survival (MFS), either alone or in combination with ADT, and improves overall survival when combined with ADT. 

Prof. Tombal concluded by referring to the EAU Guidelines on second-line therapy after treatment with curative intent. The recommendation states not to offer ADT to M0 patients with a PSA-doubling time greater than 12 months. Enzalutamide, with or without ADT, should offered to M0 patients with a high-risk BCR, defined as a PSA-doubling time of ≤ 9 months and a PSA level of ≥ 2ng/mL above nadir after radiation therapy or ≥ 1 ng/ml after radical prostatectomy with or without postoperative radiation therapy. Stop treatment if PSA nadir reaches ≤ 0.2 ng/ml at 9 months. 

In her lecture on ‘Who can really benefit from MDT in oligorecurrent HSPC?’ Prof. Barbara Jereczek-Fossa (IT) said that this treatment option can be a window of opportunity for patients and reduce treatment burdens. 

In her opinion, the biological rationale for treating metastases locally include eradication of visible disease burden, delaying systemic therapy, and postpones castration resistance. “The concept is to intervene early before widespread dissemination, MDT. This positives of this are low toxicity, low cost and low impact on quality of life.” She shares the consensus that there are currently two strategies possible with MDT, alone (which may delay ADT), or combined (there is data suggesting MDT plus short-course ADT.) The role of systemic intensification is under investigation. She stressed that a multidisciplinary decision is essential when reviewing options. 

According to Prof. Jereczek-Fossa, not all oligorecurrences are equal, so patient selection is crucial. “The likely best candidates are those with low metastatic burden (fewer than 3-5 lesions), long PSA doubling time, hormone-sensitive disease, no visceral metastasis, all lesions are treatable, and they are PSMA-negative elsewhere. Poor candidates are those with rapid PSA kinetics, multiple nodal chains, and early polymetastatic disease”.

She cited the paper ‘Integrating systemic therapy and metastasis-directed therapy in oligometastatic hormone-sensitive prostate cancer’, by Shi X. et al to illustrate how much biology really does matter. The ORIOLE and STOMP trials (MDT ± ADT) demonstrated that tumours with HiRi mutations (TP53, BRC1/2, ATM, RB1) had a worse prognosis, with the benefit of ADT concentrated in these HiRi-mutated tumours. The EXTEND trial (ADT ± MDT) further indicated that durable responders showed Th1 cytokines and increased CD8* proliferation, reflecting stronger immune activation. MDT + ADT produced greater systemic immune stimulation, including T-cell receptor (TCR) expansion and contraction. Prof. Jereczek noted that the greatest progressive-free survival benefit occurred in patients who demonstrated TCR repertoire modulation. 

“There is already a substantial level of evidence supporting MDT in oligorecurrent PCa, though this is based on pooled individual participant data (IPD) from multiple phase II trials”, stated Prof. Amar Kishan (US) in his state-of-the-art lecture “On going practice changing trials in the oligorecurrent setting.”

Prof. Kishan cited the WOLVERINE meta-analysis (Tang et al., Lancet Oncol. 2026 Feb) which included six phase II randomised trials (n=472 patients) with a median follow up of 40.7 months. He noted that the exploratory analysis found no significant impact on PFS for CRPC status, primary treatment, metastatic site, type of imaging, or number of metastases in the overall cohort.

He also referenced the PORTAL international retrospective cohort study, a nomogram-based risk classification for predicting response to metastatic-directed stereotactic body radiotherapy in PSMA PET-staged oligorecurrent PCa. The risk-group stratification showed meaningful separation, supporting its potential use in treatment selection. 

“Ongoing RCTs largely seek to quantify the benefit of MDT in addition to standard of care (SOC) in the de novo and metachronous settings. They also seek to evaluate intensification of MDT with the addition of hormonal therapy, and the addition of radioligand or other systemic agents.”

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This Plenary Session was co-chaired by Prof. Alberto Briganti (IT) and Prof. Christian Gratzke (DE). You can watch the full webcast via the EAU26 Resource Centre, including all the lectures, debates, case discussions and live interviews.