High-dose radiation plus long-term ADT extended survival in prostate cancer

Men with intermediate or high-risk prostate cancer who underwent high-dose radiation therapy followed by a longer duration of androgen deprivation therapy demonstrated longer OS than those who underwent high-dose radiation followed by short-term androgen deprivation therapy, according to results of a randomized phase 3 trial presented at the ASTRO Annual Meeting.

Perspective from Colleen A.F. Lawton, MD, FASTRO

High-dose radiation therapy plus long-term androgen deprivation therapy (ADT) also conferred a higher rate of 5-year biochemical DFS, results showed.

“This combination is associated with a high rate of curation, control of PSA and metastasis control,” Almudena Zapatero, MD, PhD, of the department of radiation oncology at Hospital Universitario de la Princesa in Madrid, said during a press conference. “The probability of curation with this treatment is very high. It’s also a noninvasive and cost-effective treatment that is associated with very good quality of life.”

Prior studies have demonstrated the combination of conventional radiotherapy and ADT significantly reduces mortality among men with locally advanced prostate cancer. High-dose radiotherapy also independently improves clinical outcomes, Zapatero said.

However, the ideal duration of androgen deprivation in conjunction with dose-escalation radiotherapy has not been established.

In the current study, Zapatero and colleagues assessed whether a longer duration of androgen deprivation in conferred better outcomes than short-term androgen deprivation when combined with high-dose radiotherapy.

The multicenter study included 355 men enrolled at nine cancer centers in Spain. All patients had cT1c — T3aN0M0 prostate cancer with no metastases, no lymph node involvement and PSA levels <100 ng/mL. All men had intermediate (n=166) or high (n=189) risk factors as defined by National Comprehensive Cancer Network criteria.

Zapatero and colleagues assigned 178 men to the short-term regimen, which consisted of 4 months of neoadjuvant and concomitant androgen deprivation plus high-dose radiotherapy (mean dose, 78 Gy). The 177 men assigned to long-term androgen deprivation underwent the same initial regimen, followed by an additional 24 months of adjuvant goserelin (Zoladex, AstraZeneca), a luteinizing hormone that suppresses testosterone production. The number of intermediate-risk and high-risk patients were comparable between groups.

Median follow-up was 63 months.

Biochemical DFS and radiation-related side effects served as primary endpoints. OS, cancer-specific survival and metastasis-free survival served as secondary endpoints.

Twenty-three patients assigned the short-term regimen and seven assigned the long-term regimen experienced biochemical failure (P=.003).

Patients assigned the long-term regimen demonstrated significantly longer 5-year biochemical DFS (89.8% vs. 81.3%; P=.019). Researchers also observed higher rates of 5-year metastasis-free survival (93.6% vs. 83.4%; P=.009) and OS (94.8% vs. 86.1; P=.01) among patients assigned the long-term regimen.

When researchers analyzed OS data by risk subgroup, results showed the benefit was more evident in patients with high-risk prostate cancer (P=.01), Zapatero said.

Incidence of grade ≥2 radiation-related adverse events were low, and rates were comparable between the two treatment groups, researchers wrote.

“Rapid and ongoing advances in treatment options require that physicians consider options that can impact both survival and quality of life,” Zapatero said in a press release. “The 5-year results of our study show that the combination of high-dose external radiotherapy utilizing new technologies — such as IMRT, VAMT and IGRT — and 28 months of hormone therapy are a very successful combination to achieve positive prostate cancer control. Of paramount consideration, long-term androgen deprivation therapy in combination with high-dose radiation therapy provides good quality of life through a noninvasive, safe and efficient treatment approach for patients with high-risk prostate cancer.”

For more information:

Zapatero A. Abstract #PL-02. Presented at: ASTRO Annual Meeting; Sept. 14-17, 2014; San Francisco.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Colleen A.F. Lawton, MD, FASTRO

As we added hormone therapy to radiation for our patients with high-risk prostate cancer and we bumped up the doses, each of these were incremental improvements in our cancer care with regard to quality of life and OS for these patients. We have been wondering for a long time, if we combined them, would it be even better? We found out [with this study] that it is. We’ll still need that long-term hormone therapy, especially for our most aggressive cancers. As much as quality of life is important to us, there still are patients with aggressive prostate cancers who could die of their disease. We have to be sure we get them past their disease so they can have some quantity — and therefore, quality — of life.

Colleen A.F. Lawton, MD, FASTRO

Vice chair, Department of Radiation Oncology, Medical College of Wisconsin

Disclosures: Lawton reports no relevant financial disclosures.