Paul L. Nguyen, MD, senior physician, director, Genitourinary Clinical Center for Radiation Oncology, Dana-Farber Cancer Institute, professor of radiation oncology, Harvard Medical School, discusses primary findings from the phase 2 FORMULA-509 trial (NCT03141671) in prostate cancer.

The multicenter, open-label trial randomly assigned patients to receive salvage radiation with 6 months of a gonadotropin-releasing hormone (GnRH) with either bicalutamide or abiraterone acetate (Zytiga), apalutamide (Erleada), and prednisone (AAP), Nguyen begins.

Patients in this trial displayed detectable prostate-specific antigen (PSA) levels and unfavorable features after radical prostatectomy. The study’s primary end point was PSA progression-free survival (PFS), and the secondary end point was metastasis-free survival (MFS) as determined by conventional imaging techniques. Median follow-up occurred at 34 months.

The study was powered to detect a hazard ratio (HR) of 0.50 for PFS and 0.30 for MFS, Nguyen says. In the primary analysis of the trial, the 3-year PFS rate was 74.9% with AAP plus SOC regimenvs 68.5% with the SOC regimen alone. The 3-year MFS rate was 90.6% vs 87.2%, respectively. Associated HRs were 0.71 for PFS and 0.57 for MFS, Nguyen states. 

Although both PFS and MFS were numerically superior, they did not meet the prespecified threshold for statistical significance, Nguyen says. However, there is still a potential signal for survival benefit, Nguyen qualifies. Survival data may reach significance with longer follow-up, Nguyen adds.

Preplanned analyses of subgroups according to stratification factors were also conducted, Nguyen continues. Interestingly, the analysis showed that patients with a PSA level greater than 0.5 ng/mL experienced a statistically significant PFS and MFS benefit, he says. Moreover, the absolute improvement in MFS benefit was 18.2% at 3 years, which is a powerful effect size, Nguyen concludes. 

Editor’s Note: Dr. Nguyen reports serving as a consultant or in an advisory role for Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences; he reports receiving research funding from Astellas Pharma, Bayer, Janssen; he has stock and other ownership interests in Volatilyx (I).

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Paul L. Nguyen, MD, discusses primary findings from the phase 2 FORMULA-509 trial in prostate cancer.

Dr. Nguyen on Primary Analysis of the FORMULA-509 Trial in Prostate Cancer

Paul L. Nguyen, MD, senior physician and director of Genitourinary Clinical Center for Radiation Oncology at Dana-Farber Cancer Institute, as well as a professor of radiation oncology at Harvard Medical School, discusses treatment considerations in high-risk prostate cancer.

Patients with high-risk prostate cancer should be considered for radiation therapy plus a brachytherapy boost and 2 years of hormone therapy, Nguyen explains.

Patients who undergo a radical prostatectomy with unfavorable disease features should receive early salvage therapy without adjuvant therapy, Nguyen says.

In Nguyen’s practice, most patients with high-risk prostate cancer receive 6 months of hormone therapy plus salvage radiation.

However, for patients with favorable disease features such as pathologic T2 disease, a Gleason score of 7, a positive margin, and a very low prostate-specific antigen level, radiation therapy may be offered alone, as androgen deprivation therapy may provide little additive benefit, concludes Nguyen.

Paul L. Nguyen, MD, discusses treatment considerations in high-risk prostate cancer.



Dr. Nguyen on Treatment Considerations in High-Risk Prostate Cancer

Paul L. Nguyen, MD, senior physician and director of Genitourinary Clinical Center for Radiation Oncology at Dana-Farber Cancer Institute, as well as a professor of radiation oncology at Harvard Medical School, discusses standard and investigational treatment options in high-risk prostate cancer.

Typically, patients with high-risk prostate cancer are treated with standard androgen deprivation therapy with a gonadotropin-releasing hormone agonist plus an antiandrogen, Nguyen says. However, novel agents are in development to try to improve upon standard treatment. 

For example, enzalutamide (Xtandi) is currently being tested in the randomized phase 3 ENZARAD trial in men with high-risk, localized prostate cancer, says Nguyen. Additionally, the phase 3 ATLAS trial is evaluating apalutamide (Erleada) in patients with high-risk disease who are receiving primary radiation therapy.

Abiraterone acetate (Zytiga) was tested in the STAMPEDE trial, Nguyen adds. Although data from study were published, the field awaits additional follow-up to determine whether patients with node-negative nonmetastatic prostate cancer derived benefit from abiraterone. 

Additionally, other studies such as the phase 3 DASL-HiCaP trial, which is evaluating darolutamide (Nubeqa) in very high-risk prostate cancer, and the phase 3 Predict-RT trial, which is evaluating abiraterone plus apalutamide in patients with high genomic risk disease, are ongoing, concludes Nguyen. 

Paul L. Nguyen, MD, discusses standard and investigational treatment options in high-risk prostate cancer.  



Dr. Nguyen on Standard and Investigational Treatment Options in High-Risk Prostate Cancer 

Paul L. Nguyen, MD, senior physician and director of Genitourinary Clinical Center for Radiation Oncology at Dana-Farber Cancer Institute, as well as a professor of radiation oncology at Harvard Medical School, discusses the optimal duration of androgen deprivation therapy (ADT) in patients with high-risk prostate cancer.

There is a lot of controversy over what the best duration of ADT is for patients with high-risk disease, says Nguyen. Two years of ADT is currently used in most randomized trials for this patient population, adds Nguyen. There is an interest in shifting toward the use of 18 months of ADT; however, the phase 3 Prostate Cancer Study IV, which compared 18 months versus 36 months of therapy, has not proven the equivalence, according to Nguyen.

Although the hazard ratio for death between 18 and 36 months on the most recent update looked reasonable, there were some issues with the study. One problem is the high dropout rate in the 36-month arm. Immediately after 18 months of treatment, numerous patients stopped receiving ADT. At 36 months, a little over half of the patients were still on therapy, says Nguyen. When there is a very high dropout rate, it tends to lean toward a bias for equivalence, concludes Nguyen.

Paul L. Nguyen, MD, discusses the optimal duration of androgen deprivation therapy in patients with high-risk prostate cancer.

Dr. Nguyen on the Optimal Duration of ADT in High-Risk Prostate Cancer

Paul L. Nguyen, MD, senior physician and director of Genitourinary Clinical Center for Radiation Oncology at Dana-Farber Cancer Institute, and a professor of radiation oncology at Harvard Medical School, discusses future research in high-risk prostate cancer.

Future research efforts in high-risk prostate cancer should focus on personalizing therapy ​for patients, says Nguyen. For example, ​a one-size-fits-all approach is currently utilized with androgen deprivation therapy.

As such, the field is anticipating results from the phase 3 Predict-RT trial​, which will use genomics to assist in the personalization of therapy for patients​, explains Nguyen.

Additionally, future research efforts are focused on minimizing the adverse effects associated with hormone therapy by using genomic markers to inform deintensification strategies. Both emerging approaches continue to garner significant excitement in the space, Nguyen concludes.

Paul L. Nguyen, MD, discusses future research in high-risk prostate cancer.

Dr. Nguyen on Future Research in High-Risk Prostate Cancer

Paul L. Nguyen, MD, senior physician and director ofGenitourinary Clinical Center for Radiation Oncology at Dana-Farber Cancer Institute, as well as a professor of radiation oncology at Harvard Medical School, discusses the utility of adding a brachytherapy boost to radiation therapy in the ASCENDE-RT trial.

In the ASCENDE-RT trial, investigators examined patients with unfavorable intermediate- or high-risk prostate cancer and found that the addition of a brachytherapy boost to standard radiation reduced the risk of disease recurrence by half, says Nguyen. Moreover, after 9 years, the rate of biochemical recurrence-free survival (RFS) improved from 63% to 83%. 

For high-risk patients, the rate of biochemical RFS was also improved, going from 58% to 78%. These data highlight that it is important to offer the brachytherapy boost, especially for high-risk patients, stresses Nguyen.

Thus far, improvements in metastasis-free survival or overall survival have not yet been observed. More adverse effects have been observed with the regimen, meaning patients must be selected carefully. For most young and healthy patients, this therapy should be offered in order to maximize the chance of cure, minimize the psychological distress of potential recurrence, and minimize the chance of going on lifelong androgen deprivation therapy after recurrence, concludes Nguyen.

Paul L. Nguyen, MD, discusses the utility of adding a brachytherapy boost to radiation therapy in the ASCENDE-RT trial.

Dr. Nguyen on the Utility of a Brachytherapy Boost in the ASCENDE-RT Trial

Paul L. Nguyen, MD, senior physician and professor of radiation oncology, Harvard Medical School, director, Genitourinary Clinical Center for Radiation Oncology, Dana-Farber Cancer Institute, discusses the role of radiation therapy in high-risk prostate cancer.

Typically, patients with high-risk prostate cancer who require radiation therapy are treated with a standard 2-year duration of hormonal therapy, Nguyen says. However, there remains some debate as to the optimal duration of hormonal treatment. 

Ultimately, most randomized clinical trials are evaluating 2 years of hormonal therapy, adds Nguyen. 

In Nguyen’s practice, he advocates for the ASCENDE-RT regimen of pelvic irradiation, ranging from 46 Gy to 50.4 Gy plus a brachytherapy boost. 

Moreover, the combination of radiation therapy and a brachytherapy boost appears to be the optimal regimen for men with high-risk prostate cancer, concludes Nguyen. 

Paul L. Nguyen, MD, discusses the role of radiation therapy in high-risk prostate cancer.   



Paul L. Nguyen, MD

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