An Update of the Phase III Trial Comparing Whole-Pelvic (WP) to Prostate Only (PO) Radiotherapy and Neoadjuvant to Adjuvant Total Androgen Suppression (TAS): Updated Analysis of RTOG 94-13
Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 17 de octubre del 2005
Presenter: C. A. Lawton Presenter's Affiliation: Medical College of Wisconsin Type of Session: Scientific
There is much interest in both the use and timing of androgen suppression during external beam radiation treatment of intermediate- to high- risk prostate cancer patients. Furthermore, there is debate regarding the optimal radiation field design to encompass all areas of known and potential disease. This trial was designed to evaluate whole pelvic versus prostate-only radiation fields, as well as neoadjuvant/concurrent versus adjuvant hormone therapy. Preliminary results were published in 2003, and this abstract provides an update of that data.
Materials and Methods
Prospective randomized trial of 1292 eligible patients (out of 1323 total patients ) enrolled between April 1, 1995 and June 1, 1999
Eligible patients included those with clinically localized adenocarcinoma of the prostate; PSA<100 ng/ml; negative bone scan; Karnofsky score ≥70; no prior radiation, chemotherapy, or hormone therapy; normal liver function tests; and >15% risk of nodal involvement by the Roach formula
Patients with bulky nodal disease detected by CT imaging were not eligible
Patients were randomized to 1 of 4 treatment arms:
PO radiation + neoadjuvant/concurrent androgen suppression
PO radiation + adjuvant androgen suppression
Stratification was based on T stage, PSA, and Gleason score
Total androgen suppression was achieved via daily flutamide with monthly goserelin or leuprolide: neoadjuvant/concurrent treatment began 2 months prior to radiation and continued until the end of radiation, whereas adjuvant treatment began following radiation and continued for a total of 4 months
All radiation was delivered via a 4-field arrangement: WP radiation consisted of 50.4 Gy to the pelvis followed by 19.8 Gy boost to prostate in 180 cGy fractions, whereas PO radiation consisted of 70.2 Gy to the prostate in 180 cGy fractions
PSA failure was defined as 2 consecutive rises, or a PSA >4 ng/ml at the last follow-up after PSA nadir was reached
Median follow-up of 5.9 years for all patients
Median age of all patients was 70 years; 73% patients had Gleason score >7; 67% patients had >T2C disease; median PSA was 23 ng/ml
With respect to progression-free survival (PFS), there was a statistically significant difference between WP + NHT and both PO + NHT (p=0.0041) and WP + AT (p=0.0045)
WP + NHT also showed a trend in PFS versus PO + AHT (p=0.0656)
5 year PFS rates for WP + NHT, PO + NHT, WP + AHT, and PO + AHT were 48.3%, 36.8%, 38.1%, and 40.4%, respectively
With respect to biochemical failure (BF), there was a statistically significant difference between WP + NHT and PO + NHT (p=0.0070)
WP + NHT also showed a trend in BF versus WP RT + AHT (p=0.0699)
5 year BF rates for WP + NHT, PO + NHT, WP + AHT, and PO + AHT were 35.9%, 45.5%, 42.8%, and 40.0%, respectively
No difference in either cause-specific or overall survival (OS) has been observed
5 year OS rates for WP + NHT, PO + NHT, WP + AHT, and PO + AHT were 81.6%, 77.8%, 75.5%, and 81.2%, respectively
WP + NHT was associated with improved PFS over PO + NHT and WP + AHT, with a trend towards improvement over PO + AHT.
WP + NHT was associated with improved BF over PO + NHT and trended towards improvement over WP + AHT.
Longer follow-up is necessary to confirm these findings and further evaluate survival.
This study suggests that if whole pelvis radiotherapy is employed to treat intermediate or high-risk prostate cancer, it should be done so with neoadjuvant and concurrent total androgen suppression, in light of slight but statistically significant improvements in progression-free survival and biochemical failure. However, since the majority of the patients in the study would be considered high-risk, the dose of radiation utilized (70 Gy) is probably inadequate based on published prostate radiation data. Thus, the problem of local failure could, in time, overwhelm any potential differences that would be seen between differing radiation fields or hormone therapy timing. Unlike the preliminary results published by Roach in 2003, there was no statistical difference found in this update between whole pelvis and prostate-only radiation. Additionally, as in the 2003 report, there remained no significant difference between neoadjuvant/concurrent and adjuvant hormone treatment. This leads to one possible conclusion that the differences between arms seen earlier in this trial may have slightly degraded over time, thereby weakening the argument for whole pelvis radiation. It will be quite interesting to follow these results as the study matures, particularly with regards to survival data.