How are biomarkers advancing treatment?
The Plenary Session “Biomarkers to guide peri-operative management in onco-urology” chaired by Prof. Alberto Briganti (IT) and Dr. Elena Castro (ES) reviewed peri-operative therapies for prostate, bladder, and kidney cancer, as well as DNA damage response genes, and the role of ctDNA (circulating tumour DNA).
In his lecture on the current landscape of peri-operative therapies in bladder (BCa) and kidney cancer (RCC), Dr. Philippe Spiess (US) stated: “The integration of immunotherapy (IO) in the management of BCa and RCC, both in the neoadjuvant and adjuvant setting is rapidly expanding. Novel agents, whether alone or in combination, offer new horizons in clinical care”.
Dr. Spiess: “For muscle-invasive bladder cancer (MIBC), the significant response rates observed with neoadjuvant IO agents raise important questions about if and when consolidative surgery is necessary in a substantial subset of patients. This remains an active area of research, particularly in defining complete response (CR) to these agents.”
Regarding locally advanced RCC, he highlighted: “Adjuvant IO, most notably with pembrolizumab, is believed to improve overall survival (based on the Keynote-564 trial). However, discrepancies across several trials in this disease space raise attention of the need to identify optimal biomarkers for treatment response, such as artificial intelligence (AI), radiomics, tissue/urinary signatures.”
Prof. Martin Gleave (CA) presented on the ‘Current landscape of peri-operative therapies in prostate cancer’, stating that neoadjuvant studies aim to reduce local and metastatic recurrence, but none have yet to become standard of care. “Despite improved survival with ADT + docetaxel or ARPI doublets in mCSPC, pathological complete response (pCR) rates remain low (<8%) when using neoadjuvant in high-risk localised PCa. Prof. Gleave cites the Phase III PROTEUS study, set to be released later this year, which is anticipated to be a practice-changing paper.”
He added: “Neoadjuvant models test novel combinations based on depth of response and emergent resistance. This presents a window of opportunity for trials that support mechanistic or pharmacokinetic/pharmacodynamic (pk/pd) drug development.”
Prof. Gleave shared findings from his Genomic Umbrella Neoadjuvant Study (GUNS), which evaluated ARPI combination therapies in high-risk localised PCa, with a focus on biomarker-driven effects on pathologic response (pCR or <5 mm MRD). “Higher rates of MRD in SP-1 patients treated with APRI triplet vs. doublet are of interest and support further evaluation with second stage expansion of SP-1.”
The future of biomarkers
“The complexity and prognostic heterogeneity of oncological pathologies make it necessary to apply precision diagnostics,” stated Prof. Valeria Panebianco (IT) in her lecture ‘Imaging as a biomarker.’ She illustrated how imaging morpho and functional pattern, RADS, and scores can be considered as biomarkers. “Computational methods is a new technique that can be used to achieve the goals of precision medicine. Network analysis produced by AI by integrating imaging data with omics data can identify specific biomarkers for disease.” As a future perspective, Prof. Panebianco presented the Digital Twin, a collection of data from different sources to present a definitive outcome, establishing a virtual pathway.
In his lecture on ‘Biomarker discovery: From bench to bedside, Prof. Lars Dyrskjøt (DK) provided background information on the long process from the discovery of biomarkers to the point where they can be used in the clinic. “Biomarker translation is challenging due to biological complexity, technical issues, clinical validation, and regulatory barriers.”
According to Prof. Dyrskyøt, the strategies to accelerate clinical application include collaborative networks such as multi-disciplinary engagement, public-private partnerships, innovative clinical trial designs, global efforts for standardisation, as well as real-word evidence and early regulatory engagement.
DNA
Prof. Kent Mouw (US) presented on ‘Bladder-sparing strategies: DNA damage response (DDR) genes and liquid biopsies.’ According to Prof. Mouw, DNA damage repair (DDR) gene alterations are associated with high pCR rates and improved outcomes in some neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) cohorts, but which genes and which mutations are still topics of discussion. “The role of DDR gene alterations status in guiding bladder preservation is uncertain. We are awaiting results from the Alliance and RETAIN-2 trials. The ctDNA dynamics appear to correlate with metastatic disease in trimodality therapy (TMT) cohorts. The direction we all want to go in is a multimodal biomarker integration (ctDNA, mpMRI, genomics (DNA/RNA), AI).”
Dr. John Sfakianos (US) stated “ctDNA is a promising predictive and prognostic biomarker” in his lecture ‘BCa: Role of ctDNA in treatment de-escalation’. He summarised that precystectomy ctDNA, derived from the transurethral resection of bladder tumour (TURBT) specimen, predicts both final pathological outcomes and long-term prognosis, regardless of clinical staging.
“ctDNA can be used in the neoadjuvant setting to support treatment de-escalation, both for neoadjuvant chemotherapy and surgery. And it can also be used to help improve surveillance regimens, reducing the need for frequent imaging,” said Dr. Sfakianos.
You can watch the full webcast via the EAU25 Resource Centre.