Metastatic Hormone-Sensitive - January - February 2023

This issue covers some of the advances made in treating men with metastatic prostate cancer who have not yet received hormonal therapy.

In patients with high-volume metastatic disease, the current standard treatment is the combination of hormonal therapy with docetaxel chemotherapy. In patients healthy enough to tolerate the addition of chemotherapy, the addition of docetaxel results in much better survival.

One major advance reviewed in this issue is the impact of adding either abiraterone or daurolutamide to the combination of hormonal therapy with docetaxel. In patients with large-volume disease, the addition of the third drug results in improved cancer control. Note that both trials looked at adding additional testosterone blockade to the hormonal therapy plus docetaxel combination. This leaves open the question of whether it is beneficial to add docetaxel to the combination of hormonal therapy and abiraterone or daurolutmide.

For the last several years of prostate cancer treatment, there have been two schools of thought about when to initiate therapy in men with recurrent prostate cancer. One school has favored delaying treatment until symptoms or medically threatening disease develop. Advocates of this approach note that cancer treatment is toxic and delaying treatment might offer patients a longer period of high quality of life.

The second school of thought noted that the risk of treatment-resistant cancers being present increases as cancer cells increase. Thus, the high-volume disease is more likely either resistant before therapy starts or emerges earlier once treatment has started.

As this issue illustrates, which approach is correct depends on the treatment context. For example, docetaxel is an effective addition when added to hormonal therapy for high volume, but not low volume disease. In contrast, it appears that drugs like abiraterone, enzalutamide, apalutamide or daurolutamide, originally introduced for men with castration-resistant prostate cancer (CRPC), are also effective when used earlier in the course of disease.

This issue also discusses some of the challenges and opportunities for biomarker development in prostate cancer. Biomarkers are tests that can help guide treatment decisions by providing information about the tumor's molecular characteristics or the patient's response to therapy. Biomarkers can help identify patients who are more likely to benefit from a specific treatment or may need a different or more aggressive approach.

One example of a biomarker that has been approved by the FDA for prostate cancer is the prostate-specific antigen (PSA) test. PSA is a protein produced by prostate cells that can be measured in blood samples. PSA levels can indicate how well a patient is responding to hormonal therapy or other treatments. However, PSA is not a perfect biomarker, as it can be influenced by other factors, such as inflammation or benign prostatic hyperplasia (BPH).

Another example of a biomarker that is being investigated for prostate cancer is circulating tumor DNA (ctDNA). ctDNA is DNA that is released by tumor cells into the bloodstream and can be detected by sequencing techniques. ctDNA can provide information about the genetic mutations and alterations that are present in the tumor and may affect its sensitivity or resistance to certain drugs. ctDNA can also help monitor tumor evolution and progression over time.

However, some limitations and challenges are associated with biomarker development and validation for prostate cancer. For instance, not all tumors shed ctDNA into the blood, and ctDNA levels may vary depending on the tumor burden and location. Moreover, there is a need for standardized methods and criteria for biomarker testing and interpretation across different laboratories and clinical trials.

In summary, this issue provides an overview of some of the recent advances and ongoing research in the field of prostate cancer treatment and biomarker development. Click on the following link to view this issue.

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