Editor’s Note: Prostate cancer is the most common “silent killer” threatening men’s health worldwide, with traditional treatments primarily involving surgery, radiation therapy, chemotherapy, and hormonal therapy. In recent years, the PARP inhibitors has marked the beginning of precision treatment for prostate cancer, followed by numerous novel therapeutic targets and drugs entering clinical practice. In the era of precision treatment, it is essential to provide personalized comprehensive treatment decisions for prostate cancer patients through multidisciplinary teams (MDTs), aiming to extend patients’ survival and improve their quality of life. At the ASCO-GU 2024 conference, Dr. Qiang Wei from West China Hospital, Sichuan University, shared strategies for guiding precision treatment based on molecular typing of prostate cancer and his views on further MDT diagnosis and treatment for prostate cancer.
Oncology Frontier: At this year’s ASCO-GU, we see a proliferation of precision targeted treatment drugs represented by PARP inhibitors. Prostate cancer has entered the era of precision treatment. Could you share your insights on the molecular typing of advanced prostate cancer and how it guides targeted treatment?
Dr. Qiang Wei: The precision treatment of advanced prostate cancer relies on molecular typing, involving a detailed analysis of genetic characteristics. Molecular typing can reveal specific gene mutations, gene expression patterns, protein activities, and other biomarkers, providing a basis for personalized treatment.
Currently, key targets for molecular typing of advanced prostate cancer include: (1) Homologous recombination repair (HRR) gene mutations, including BRCA1/2, ATM, etc., which may benefit from PARP inhibitor treatment. (2) High microsatellite instability (MSI-H) or mismatch repair deficiencies (dMMR), indicating potential efficacy of immune checkpoint inhibitors. (3) Androgen receptor (AR) signaling pathway variations, such as AR amplification or point mutations, which may affect the effectiveness of anti-androgen therapy and indicate the need for stronger AR signaling pathway inhibitors. (4) PI3K/AKT/mTOR pathway mutations: These may suggest the potential utility of mTOR inhibitors or PI3K/AKT inhibitors.
Molecular typing of advanced prostate cancer primarily serves the following purposes. Firstly, it offers personalized treatment options. Based on the results of molecular typing, targeted therapeutic drugs can be chosen, such as selecting PARP inhibitors for patients carrying BRCAm, or considering immune checkpoint inhibitors for those with MSI-H/dMMR, as they might be more sensitive. Patients with AR signaling pathway anomalies might develop resistance to AR signaling pathway inhibitors. Secondly, it allows for dynamic monitoring of treatment. Regular molecular typing can assess treatment effectiveness and the genetic evolution of the tumor, facilitating timely adjustments to the treatment plan. Thirdly, it aids in prognostic assessment. The presence of molecular markers can help predict disease progression and patient survival outcomes, guiding follow-up plans and treatment decisions. Fourthly, it provides molecular-level decision-making information for the comprehensive management of prostate cancer, meaning that on top of traditional clinical and pathological characteristics, molecular typing results can be integrated to develop comprehensive disease management strategies, bringing prostate cancer management to a molecular and genetic level.
In summary, with advances in molecular biology and the application of high-throughput sequencing technologies, precision treatment for advanced prostate cancer is gradually becoming a reality. By integrating molecular typing information, doctors can more accurately tailor treatment plans for each patient, enhancing treatment outcomes and improving patient prognosis.
Oncology Frontier: For patients with advanced prostate cancer, we increasingly advocate for providing comprehensive diagnostic and treatment plans through multidisciplinary communication. Why should we still emphasize multidisciplinary team (MDT) when mCRPC has entered the end-stage?
Dr. Qiang Wei: Metastatic castration-resistant prostate cancer (mCRPC) is at the terminal stage, where extending survival and improving quality of life are the main goals of treatment. However, patients at this stage often have poor physical condition and may have multiple, complex tumor-related comorbidities, increasing the difficulty of treatment. Therefore, the importance of multidisciplinary team (MDT) cannot be overlooked. MDT collaboration enables experts from different fields to come together to develop the best treatment plan for the patient, ensuring comprehensive and personalized treatment even in the late stages of the disease. MDT plays a crucial role in the decision-making process for mCRPC in the following areas.
Firstly, in terms of genetic testing and molecular typing guidance, urologists, medical geneticists, molecular biologists, and others can jointly analyze the results of genetic tests and molecular typing to determine whether a patient is suitable for a certain targeted treatment or drug trial, thus providing a targeted treatment plan.
Secondly, in comprehensive treatment decision-making, an MDT team including radiation oncology, oncology, pathology, radiology, and other multidisciplinary experts can take into account the tumor’s location, size, biological characteristics, and the patient’s overall condition. From different disciplinary perspectives, they can offer personalized comprehensive treatment decisions for the patient, including radiation therapy, chemotherapy, hormonal therapy, and various emerging treatments, providing an efficient and safe optimal treatment plan.
Thirdly, in adverse reaction management, as different treatment drugs or methods have various side effects, especially since many prostate cancer patients are elderly with complex underlying diseases, and patients in the mCRPC stage have poorer physical conditions, antitumor treatment may trigger various adverse reactions. In addition to different clinical disciplines assisting in the assessment and management of adverse reactions, pharmacology experts, case managers, and nursing staff in the MDT team can provide professional medication management advice and symptom relief measures, helping patients better cope with side effects.
Fourth, in enhancing quality of life, the purpose of palliative care is not only to extend life but more importantly, to improve or maintain quality of life. At this stage, pain management specialists, nutritionists, psychological counselors, and rehabilitation therapists are crucial components of the MDT. They can assist patients in managing the physical and psychological issues throughout the course of the disease.
Fifth, in formulating personalized diagnostic and treatment plans, the MDT can tailor plans based on the specific circumstances of the patient, including the stage of the disease, patient preferences, and expected goals.
Therefore, even during the palliative treatment phase of mCRPC, the collaboration of an MDT is crucial. It not only provides the latest treatment information and technology but also ensures that patients receive comprehensive care and support, maximizing the improvement of patients’ quality of life and treatment outcomes.
Oncology Frontier: What suggestions and ideas do you have on how to improve the MDT treatment of prostate cancer in China?
Dr. Qiang Wei: The level of MDT diagnosis and treatment for prostate cancer in China still has a gap compared to abroad. Some prostate cancer treatment centers overseas integrate clinical, pathological, imaging, and other multidisciplines, offering patients one-stop, full-process diagnostic and treatment services. There are explorations of integrated diagnosis and treatment of prostate cancer in China, but the scale and system are still insufficient and not yet perfected.
To enhance the MDT diagnosis and treatment level for prostate cancer in China, we need to promote and perfect the following aspects. First, develop standard operating procedures for MDT work, clarifying the roles and responsibilities of specialists from different disciplines to ensure the efficiency and quality of teamwork. Second, establish a regular MDT consultation system to discuss difficult cases regularly, jointly formulate and adjust treatment plans. Third, create a quality control and effectiveness assessment system for MDT work, regularly evaluating and providing feedback on the MDT’s work to continuously optimize the workflow. Fourth, provide comprehensive patient education to help patients and their families understand the treatment process for prostate cancer and the importance of MDT, enhancing patient acceptance and satisfaction with the MDT model. Lastly, encourage interdisciplinary communication and collaboration, regularly organize academic conferences and seminars related to prostate cancer to promote the exchange of the latest medical knowledge and technologies.
