Non-metastatic castration-resistant prostate cancer (nmCRPC) is a stage of prostate cancer where the disease progresses despite low testosterone levels, but has not yet spread to distant parts of the body. Specific medications are available to manage this condition and delay its progression.
Understanding Non-Metastatic Castration-Resistant Prostate Cancer
Non-metastatic castration-resistant prostate cancer (nmCRPC) describes prostate cancer that continues to grow even when testosterone levels are significantly suppressed, typically below 50 nanograms per deciliter (ng/dL), a state known as “castration-resistant.” This resistance often develops after androgen deprivation therapy (ADT) or surgical castration, which aims to stop the cancer’s growth by reducing male hormones that fuel it.
The “non-metastatic” aspect means that conventional imaging techniques, such as bone scans or computed tomography (CT) scans, do not show evidence of the cancer having spread to other organs or bones. While the cancer is still localized or confined to the pelvic region, a rising prostate-specific antigen (PSA) level in the blood indicates that the disease is progressing. Distinguishing this stage is important because it guides treatment decisions focused on delaying the cancer’s spread and improving patient outcomes. Most men with nmCRPC do not experience symptoms, with a rising PSA being the primary indicator of progression.
Medications for Non-Metastatic Castration-Resistant Prostate Cancer
For men with nmCRPC, the primary medications used are a class of drugs known as next-generation androgen receptor pathway inhibitors. These include apalutamide, enzalutamide, and darolutamide. These medications are specifically designed to target the androgen receptor pathway, which is a key driver of prostate cancer growth, even when testosterone levels are low.
The purpose of these therapies is to delay the onset of metastasis, which is when the cancer spreads to distant parts of the body. Clinical trials, such as SPARTAN (for apalutamide), PROSPER (for enzalutamide), and ARAMIS (for darolutamide), have demonstrated that these drugs can significantly prolong metastasis-free survival and overall survival in men with nmCRPC who have a rapidly rising PSA. These medications represent a standard of care for patients in this specific disease stage.
How These Medications Work
These next-generation androgen receptor pathway inhibitors function by interfering with the androgen receptor (AR) pathway, which prostate cancer cells utilize for growth. These drugs are also more potent and specific than older antiandrogens.
These medications work by several mechanisms to disrupt the AR pathway. They competitively inhibit the binding of androgens (male hormones) to the AR with higher affinity than first-generation agents. They also impair the movement of the AR into the cell nucleus, where it would normally bind to DNA and activate genes involved in cancer growth. Furthermore, they obstruct the AR-mediated transcription process, preventing the cancer cells from receiving the necessary growth signals.
Managing Treatment and Side Effects
Treatment for nmCRPC with these medications may cause various side effects. Common side effects can include fatigue, high blood pressure (hypertension), falls, skin rash, and joint pain (arthralgia). Some patients taking apalutamide have reported seizures in a small percentage of cases, and hypothyroidism has also been observed.
Managing these side effects often involves close monitoring by the healthcare team and supportive care. For instance, blood pressure may need regular checks and medication adjustments. Patients may also be advised on strategies to reduce the risk of falls, such as physical therapy or home modifications. Ongoing monitoring of prostate-specific antigen (PSA) levels and periodic imaging scans are also conducted to track the cancer’s progression and assess how well the treatment is working. Open communication between the patient and their doctor is important to address any side effects promptly and ensure adherence to the treatment plan.