Mayo Clinic

Neoadjuvant or Adjuvant Therapy?

Parminder Singh, MD, Assistant Professor of Hematology and Oncology at Mayo Clinic in Phoenix, Arizona, discusses the future of care for muscle-invasive bladder cancer (MIBC) in this 14-minute talk. Two large trials–one SWOG trial from 2003 evaluating methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) prior to cystectomy, and an international trial reporting on cisplatin, methotrexate, and vinblastine (CMV) prior to cystectomy or radiation–both famously showed improved survival in MIBC patients. Because of this data, neoadjuvant chemotherapy (NAC) became the gold standard for care. Since then, research in this area has focused on fine-tuning drug options and patient selection under the NAC framework, such as evaluating MVAC versus gemcitabine and cisplatin (GC), options for cisplatin-ineligible patients, and how pathological responses to NAC affect survival. However, Singh suggests this space of MIBC management is ready to move into a new chapter due to antibody-drug conjugates. The current data about these emerging drugs is promising. There is evidence that patients who priorly did not respond to chemotherapy had improvements in overall survival with enfortumab vedotin (EV). Currently, there is a mock trial comparing EV, pembrolizumab, and GC in cisplatin ineligible patients at the Mayo Clinic. Singh is optimistic EV and pembrolizumab may be able to replace cisplatin for those who are ineligible in the future.

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Just the Beginning: What’s Next for Radiotheranostics in Prostate Cancer?

Geoffrey B. Johnson, MD, PhD, Chair of the Division of Nuclear Medicine at the Mayo Clinic in Rochester, MN, discusses 177Lu-PSMA-617 treatment for castration-resistant metastatic prostate cancer (mCRPC) along with other advances in theranostics. He reviews how drug treatments target prostate-specific membrane antigen (PSMA) receptors, then highlights the VISION trial which tested 177Lu-PSMA-617 on patients who had previously undergone chemotherapy and hormone therapy. This trial found that patients with advanced prostate cancer had well-tolerated side effects, leading to studies like PSMAfore with patients who had not started chemotherapy. Dr. Johnson points out several drawbacks of 177LuPSMA-617, namely that it does not cure prostate cancer, there are dosing limitations, it is very expensive, and not all prostate cancer patients can be treated with it. He also notes that not all prostate cancer tumors express PSMA thereby reducing the benefit of 177LuPSMA-617. Dr. Johnson then describes combination therapies using hormonal therapy, chemotherapy, immunotherapy, external radiation, cocktail radionuclide therapy, and external radiation. Finally, he presents new technologies like PSMA post-therapy imaging, strategies to improve efficacy of cell binding, and targeting agents such as fibroblast activation protein (FAP) inhibitors.

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Genetic Testing & Next Generation DNA Sequencing

Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, discusses genetic testing, next generation DNA sequencing, and the genetic diversity of prostate cancer (PCa) in regard to treatment. He begins by reviewing the germline BRCA mutations, stating that BRCA1 and BRCA2 mutations individually make up fewer than 1.3% of all cases of localized PCa. Dr. Bryce then discusses BRCA2 in detail, focusing on how BRCA2 carriers are considered high risk by the NCCN guidelines, which recommend PSA screening discussions to start at age 45. He evaluates traditional guidelines in the context of germline mutations, finding that genetic testing and Gleason score guidelines do not reliably identify PCa patients for the presence/absence of high-risk germline mutations. Dr. Bryce then discusses the mutational landscape by disease state, displaying how PCa evolves as it advances to become metastatic and castration resistant and supporting the idea that a genomic understanding of an individual’s disease is key to treatment. He reviews the approval of olaparib, a PARP inhibitor, and the PROfound trial. Dr. Bryce concludes that inherited prostate cancer risk syndromes are under-recognized, both in practice and in research, that PCa is genetically diverse, that the impact of treatments on tumor evolution should be evaluated, and that multiple new pathways for therapeutic targeting have been identified.

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