How to cite: Taplin ME. Biomarkers in Advanced Disease. Grand Rounds in Urology. February, 2026. Accessed Oct 2026. https://grandroundsinurology.com/biomarkers-in-advanced-disease/
Summary
Mary-Ellen Taplin, MD, Professor of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts, reviews the role of biomarkers in advanced prostate cancer, emphasizing their dual function as prognostic and predictive tools that inform clinical decision making. She defines biomarkers as measurable characteristics that reflect tumor biology, prognosis, or response to therapy, and highlights that some biomarkers, such as BRCA mutations, can serve both roles.
Dr. Taplin begins with established clinical biomarkers, including prostate-specific antigen (PSA) kinetics. PSA doubling time remains a strong prognostic marker, with shorter doubling times associated with worse outcomes and used as a key eligibility criterion in trials such as EMBARK. She also emphasizes PSA nadir as a critical biomarker, where failure to achieve a nadir below 0.2 is associated with inferior survival across multiple treatment settings, including androgen deprivation therapy, chemotherapy, and androgen receptor pathway inhibitor–based regimens.
She highlights the importance of interpreting suboptimal PSA responses in clinical practice. In such cases, clinicians should reassess treatment adequacy, confirm castrate testosterone levels, evaluate adherence, and consider treatment intensification, including radiation therapy, metastasis-directed therapy, or escalation to triplet systemic therapy when appropriate.
Dr. Taplin then reviews emerging genomic biomarkers. The Decipher classifier, based on messenger RNA expression, provides prognostic information and may predict benefit from docetaxel in metastatic disease, helping guide decisions to intensify treatment.
DNA-based biomarkers are reviewed, including homologous recombination repair gene alterations such as BRCA1 and BRCA2, which predict response to poly (ADP-ribose) polymerase inhibitors, and androgen receptor alterations that influence response to androgen-targeted therapies. Additional biomarkers include mismatch repair deficiency, tumor mutational burden, SPOP mutation, and PTEN loss, each with potential therapeutic implications.
Dr. Taplin also emphasizes the role of prostate-specific membrane antigen positron emission tomography/computed tomography imaging as a predictive biomarker for eligibility for radioligand therapy and for response.
The International Prostate Cancer Update (IPCU), is a multi-day, CME-accredited conference focused on new developments in prostate cancer treatment, diagnosis, and prevention. IPCU 36 featured lectures, interactive discussions, panel roundtables, debates, and case reports. This conference is led by expert physicians and is designed for urologists, medical oncologists, radiation oncologists, and other healthcare professionals involved in the diagnosis and treatment of prostate cancer.
The goal of this educational program is to equip healthcare professionals involved in the diagnosis and treatment of prostate cancer with the up-to-date clinical knowledge and tools they need to best treat their patients. The program will discuss the treatment of prostate cancer from diagnosis to treating advanced and metastatic disease. The conference aims to give physicians exposure to a comprehensive review of treating prostate cancer patients and to give them a chance to discuss the issues with peers and experts.
ABOUT THE AUTHOR
Mary-Ellen Taplin, MD, is the Chair of the Executive Committee for Clinical Research in the Dana-Farber Cancer Institute (DFCI) and a Professor of Medicine at Harvard University in Boston, Massachusetts. In her role as Chair of the Executive Committee Clinical Research, Dr. Taplin oversees DFCI clinical research operations and mentors DFCI investigators in the development of trials that have the potential to improve outcomes for cancer patients. Her research in prostate cancer has focused on androgen receptor changes in the evolution of hormone-refractory prostate cancer and clinical trials of novel hormone therapy and chemotherapy with correlative molecular endpoints.
