Whole-Pelvic Radiotherapy/Neoadjuvant Hormone Therapy in Prostate Cancer Patients

SAN FRANCISCO—Whole-field radiotherapy improves progression-free survival in prostate cancer patients who have a 15% or greater risk of lymph node involvement, compared with prostate-only radiotherapy, according to a study presented at the 43rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology (plenary 5).

The study also showed a progression-free survival advantage for whole-pelvic radiotherapy plus neoadjuvant hormone therapy, compared with whole-pelvic radiotherapy plus adjuvant hormone therapy (HT), noted Mack Roach III, MD, professor of radiation oncology, University of California, San Francisco. Dr. Roach reported the results on behalf of the RTOG 9413 study group.

Between April 1995 and June 1999, the RTOG 9413 researchers enrolled 1,323 men with biopsy-proven prostate cancer, pretreatment PSA values of less than 100 ng/mL, and a risk of lymph node involvement of at least 15%. The average age of the men was 70. Nearly 25% were black. Two thirds had bulky disease, one third had PSA of 30 ng/mL or higher, and more than 70% had Gleason scores between 7 and 10.

Patients were divided into four groups:

• The first arm was treated with neoadjuvant hormone therapy for 2 months, followed by 2 months of neoadjuvant hormone therapy combined with whole-pelvic radiotherapy.

• The second arm received neoadjuvant hormone therapy for 2 months, followed by 2 months of neoadjuvant hormone therapy combined with prostate-only radiotherapy.

• The third arm was treated with whole-pelvic radiotherapy for 2 months, followed by 4 months of adjuvant hormone therapy.

• The fourth arm was treated with prostate-only radiotherapy for 2 months, followed by 4 months of adjuvant hormone therapy.

Hormone therapy consisted of oral flutamide (Eulexin) and either leuprolide (Lupron) or goseralin acetate depot (Zoladex). Whole-pelvic radiotherapy had a minimum field size of 16 cm by 16 cm, while prostate-only radiotherapy was limited to 11 cm by 11 cm.

Study Results

With a median follow-up of 59 months, 4-year progression-free survival was significantly higher in the patients treated with whole-pelvic radiotherapy and neoadjuvant hormone therapy: 61%, compared with 49% for whole-pelvic radiotherapy/adjuvant hormone therapy, 45% for prostate-only radiotherapy/neoadjuvant hormone therapy, and 47% for prostate-only radiotherapy/adjuvant hormone therapy (P = .005).

The results do not as yet show any significant difference in overall survival among the four arms, Dr. Roach said. However, he pointed out that in their investigation of patients with Gleason scores between 2 and 6 (RTOG 8610), "survival curves separated at a point beyond what has been reached in this study."

He suggested that RTOG 9413 may eventually show a significant effect of whole-pelvic radiotherapy/neoadjuvant hormone therapy on overall survival rates.

When comparing just radiation fields, the rate of progression-free survival was 56% for whole pelvic vs 46% for prostate only (P = .014). Again, there was no significant difference in overall survival (85% vs 83%, respectively).

When comparing just hormone therapy, there was no significant difference in progression-free survival between neoadjuvant vs adjuvant hormone therapy (53% vs 48%, respectively). However, "there’s a 2-month difference in the duration of therapy—6 months from the date of randomization to discontinuation of hormone therapy for adjuvant therapy vs 4 months for neoadjuvant—which might have had an impact on rates," Dr. Roach said.

He noted a trend toward an increased incidence of grade 3 or higher late gastrointestinal/genitourinary (GI/GU) toxicity in patients who received whole-pelvic radiotherapy.

"Patients with a risk of positive lymph nodes of greater than 15% have an improved progression-free survival when whole-pelvic radiotherapy is given with neoadjuvant hormone therapy," Dr. Roach concluded. He added that "longer follow-up is required to assess the ultimate impact of whole-pelvic radiotherapy and neoadjuvant hormone therapy on survival, and the optimal duration of hormone therapy remains unknown."

The discussant, Gerald Hanks, MD, formerly of Fox Chase Cancer Center, said that it is hard to compare some of the results from this study with other research, since the RTOG 9413 protocol defined biochemical failure as two, instead of three, consecutive rises in PSA.

Dr. Hanks advocated that further research be conducted to clarify some of the issues raised by the study. Specifically, he recommended further efforts to investigate the effectiveness of prostate-only, small-pelvic, and large-pelvic radiotherapy. In addition, he suggested that researchers initiate quality-of-life studies to show if the benefits of whole-pelvic radiotherapy outweigh the increased incidence of GI and GU toxicity.

In an interview, Dr. Roach noted that with the use of modern 3D conformal and/or intensity modulated radiotherapy (not required for RTOG 9413), "the trend for a difference in late GI/GU toxicity should not be a major issue."

Dr. Roach concluded: "There are two very important findings from this study. First, RTOG 9413 proves that there is a time-dependent biologic interaction between hormonal therapy and radiation. Second, it proves that a major part of this biologic interaction takes place in the pelvic lymph nodes."