Neoadjuvant Enzalutamide Prior to Prostatectomy Advancing Prostate Cancer Treatment

Neoadjuvant Enzalutamide Prior to Prostatectomy Advancing Prostate Cancer Treatment

In recent years, the treatment landscape for localized and high-risk prostate cancer has undergone a significant evolution. One of the emerging strategies showing promise is the use of neoadjuvant enzalutamide prior to prostatectomy. This approach, which involves administering targeted therapy before surgery, aims to reduce tumor burden and improve surgical outcomes. In this article, we examine what neoadjuvant therapy entails, the role of enzalutamide, and how it’s shaping the future of prostate cancer care.

Understanding Neoadjuvant Therapy

Neoadjuvant therapy refers to treatment given before the primary therapy, typically surgery, to improve its effectiveness. In prostate cancer, the primary therapy is often radical prostatectomy, which involves the surgical removal of the prostate gland.

The goals of neoadjuvant treatment include:

Shrinking the tumor

Reducing micrometastases (invisible cancer spread)

Lowering the risk of positive surgical margins

Enhancing long-term cancer control

Historically, neoadjuvant androgen deprivation therapy (ADT) using drugs like leuprolide showed modest success. However, newer agents like enzalutamide offer more potent androgen receptor inhibition, potentially leading to better results.

What Is Enzalutamide?

Enzalutamide is an oral androgen receptor inhibitor that blocks the effects of testosterone and other androgens—hormones that fuel prostate cancer growth. It’s traditionally used to treat metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC).

Unlike traditional hormone therapy, enzalutamide:

Directly blocks androgen receptors inside cancer cells

Prevents testosterone from stimulating tumor growth

Works synergistically with other hormonal agents

These characteristics have prompted researchers to investigate its effectiveness earlier in the disease course—as part of neoadjuvant treatment for high-risk localized prostate cancer.

Rationale for Enzalutamide Before Prostatectomy

Patients with high-risk or locally advanced prostate cancer have a greater chance of recurrence even after surgery. Adding a potent agent like enzalutamide before prostatectomy is intended to:

Reduce tumor volume, making surgery easier and more complete

Eliminate microscopic disease outside the prostate

Lower positive margin rates, meaning less chance of cancer left behind

Delay or prevent recurrence, improving long-term outcomes

Clinical studies have shown that enzalutamide, when combined with other agents like leuprolide or abiraterone, may lead to greater tumor shrinkage and pathologic response.

Clinical Evidence and Trials

Several phase II and phase III trials have explored the use of neoadjuvant enzalutamide:

The ENACT trial assessed enzalutamide in men with low- and intermediate-risk prostate cancer and demonstrated significant PSA suppression.

A study at Dana-Farber Cancer Institute evaluated neoadjuvant enzalutamide plus ADT prior to surgery in high-risk patients. Results showed reduced tumor size and decreased lymph node involvement.

Trials have also reported a higher rate of pathologic complete response (pCR) and minimal residual disease, which are favorable indicators for long-term control.

Although not yet a standard of care, results from ongoing trials may soon change treatment guidelines for high-risk patients.

Surgical and Pathological Considerations

When neoadjuvant enzalutamide is used before prostatectomy, surgeons may observe:

Softer, smaller tumors with better-defined margins

Fewer cancer-positive lymph nodes

Lower rates of extracapsular extension (cancer spread beyond the prostate capsule)

From a pathology perspective, pathologic response (including complete response or minimal residual disease) is a critical endpoint that correlates with improved biochemical recurrence-free survival.

These benefits contribute to cleaner resections and potentially reduced need for adjuvant therapy post-surgery.

Side Effects and Monitoring

Like all therapies, enzalutamide is associated with potential side effects, which may include:

Fatigue

Hot flashes

Joint or muscle pain

Increased risk of falls or dizziness

Rare cases of seizures

When used neoadjuvantly, treatment is typically administered for a limited duration—usually 3 to 6 months—which may reduce the intensity or duration of side effects.

Patients are closely monitored with:

PSA levels

Testosterone levels

Imaging studies

Clinical exams to assess tolerance and response

Shared decision-making with the care team helps balance efficacy and quality of life during this treatment period.

Impact on Long-Term Outcomes

While long-term survival data are still emerging, early studies suggest that neoadjuvant enzalutamide:

Delays biochemical recurrence

Reduces the need for immediate postoperative radiation or hormone therapy

May lower prostate cancer–specific mortality in select high-risk groups

As research continues, combining enzalutamide with other novel agents may further improve outcomes in aggressive cases.

Frequently Asked Questions About Neoadjuvant Enzalutamide

Is this treatment FDA-approved?

Enzalutamide is FDA-approved for advanced prostate cancer, but its neoadjuvant use is still considered investigational and is mostly offered through clinical trials.

Who is a candidate for neoadjuvant enzalutamide?

Typically, men with high-risk localized or locally advanced prostate cancer who are healthy enough for surgery and are participating in a clinical trial.

Will I still need treatment after surgery?

Possibly. The need for adjuvant therapy depends on the surgical pathology report and other risk factors. However, neoadjuvant therapy may reduce the intensity or likelihood of further treatment.

Can this therapy cure prostate cancer?

It is not a cure on its own, but when combined with surgery, it may increase the likelihood of long-term remission and cancer control.

Conclusion

Neoadjuvant enzalutamide prior to prostatectomy represents an exciting step forward in the treatment of high-risk prostate cancer. By shrinking tumors and improving surgical outcomes, this approach offers hope for better long-term disease control. While still under investigation, its potential benefits continue to be validated in clinical trials across the globe.

For patients facing aggressive prostate cancer, participating in a trial or discussing neoadjuvant options with their care team can be a proactive step toward more personalized, effective treatment. With the power of modern science and targeted therapies like enzalutamide, the future of prostate cancer care is evolving—toward greater precision, deeper remission, and improved survivorship.