Combining Targeted Therapy and Radionuclide Therapy Made a Difference in Prostate Cancer

Prostate cancer is the second most common cancer in men after lung cancer in Turkey, with approximately 19 thousand new diagnoses each year. It requires careful management because of the challenges involved in diagnosis and treatment. Around 20% of prostate cancers are advanced at diagnosis, and an estimated 6-10% of cases diagnosed at an early stage progress to metastatic, or stage 4, prostate cancer. Treatment for advanced prostate cancer therefore remains important.

Newly diagnosed prostate cancer is castration-sensitive, meaning that it responds favorably to treatment that deprives it of male hormones (androgens). Androgens, particularly testosterone, encourage prostate cancer cells to grow and multiply. Castration sensitivity means that cancer cells lose their ability to grow and spread when exposed to low levels of these hormones.

Over time, some prostate cancers may become resistant to hormone therapy and are called "castration-resistant prostate cancer" (CRPC). This means that the cancer can grow even in an environment with low testosterone levels, generally indicating the need to consider more aggressive treatment approaches.

The ENZA-P Study

Metastatic castration-resistant prostate cancer (mCRPC) treatments have played an important role in extending patients' lives. Research into new treatment combinations is nevertheless a development that offers patients greater hope. In this context, the randomized phase II trial called "ENZA-P" has emerged as an innovative approach in this field.

Combining Targeted Therapy (Enzalutamide) and Radionuclide Therapy (Lutetium)

These treatments, both separately approved for advanced prostate cancer, were tested together for the first time in a comprehensive randomized clinical trial.

An article by Louise Emmett and colleagues in The Lancet Oncology, published on 12 April 2024, examined the effects of adding lutetium-PSMA-617 to enzalutamide in patients with mCRPC. The research showed beneficial treatment effects from enzalutamide and lutetium, particularly in patients with mCRPC who had risk factors for early progression.

This open-label, randomized, controlled phase II study, conducted at 15 hospitals in Australia, enrolled men who had not previously received docetaxel or androgen receptor pathway inhibitors for mCRPC and whose disease was positive on PSMA-PET-CT . The primary focus was prostate-specific antigen (PSA) progression-free survival, defined as the time from randomization to the first evidence of PSA progression, initiation of nonprotocol cancer treatment, or death.

Study Findings

Combining lutetium with enzalutamide was shown to significantly extend PSA progression-free survival.

• Median PSA progression-free survival increased from 7.8 months with enzalutamide alone to 13 months in the group receiving added lutetium.

Common side effects included fatigue, nausea, and dry mouth, while serious side effects occurred with similar frequency in both groups.

The infographic below summarizes this combination treatment and the study.

These results indicate that the combination of enzalutamide and lutetium warrants wider evaluation in mCRPC treatment. The combination may also improve quality of life by increasing treatment response and offer an opportunity for effective intervention in the early stages of progression.

The effective combination of enzalutamide and lutetium has brought a new dimension to the treatment of advanced prostate cancer, and these study results should be viewed as a new source of hope against this challenging cancer. The ENZA-P study has had a profound impact on the course of the disease and treatment response, opening a new chapter in oncology.