March 30, 2011 (Vienna, Austria) — Ten-year follow-up results of the European Organization for Research and Treatment of Cancer (EORTC) trial 22911, which looked at outcomes for men with pathologically high-risk prostate cancer, showed that men who received adjuvant radiotherapy immediately after radical prostatectomy had significantly better survival rates than those assigned to watchful waiting after surgery in terms of biochemical progression.
Hein Van Poppel, MD, urologist from University Hospitals Leuven, Belgium, presented the 10-year follow-up results for the first time here at the European Association of Urology 26th Annual Congress. The data were the results of a longer-term follow-up to the 5-year analysis presented in 2005.
"We've shown that, after 5 years in a former analysis, there was a definite advantage for patients with immediate adjuvant radiotherapy with respect to the biochemical progression-free survival [PFS] and local relapses. We did not show an advantage for metastasis-free survival or overall survival," reported Dr. Van Poppel.
After 2005's 5-year analysis, this year's study presents new, longer-term findings that confirm the 5-year results. "The effects of an older median age in the 2 groups and the impact this has on [PFS] have been thoroughly examined," said Dr. Van Poppel.
"We know that when these patients had immediate postoperative radiotherapy, they do better, and had a longer biochemical [PFS] and clinical [PFS], especially in the case of positive surgical margins and extension of disease to the seminal vesicles. This is a very important message to the urological community," he added.
The EORTC study involved 1005 patients enrolled between 1992 and 2001, and the first 5-year analysis showing a significant difference in clinical and biochemical PFS was published in The Lancet (Bolla et al. 2005). The median follow-up is now 10.6 years. Patients were eligible if they had cT1-3N0M0 tumors treated with radical prostatectomy with adverse postoperative features of extracapsular extension, positive margins, or seminal vesicle invasion.
After surgery, patients either continued under wait-and-see management or received immediate postoperative radiotherapy of 60 Gy delivered over the course of 6 weeks. Groups were well balanced, with an average age of 65 years and median prostate-specific antigen (PSA) levels of 12.4 ng/mL (range, 0.3 - 159.4 mL) presurgery and 0.2 ng/mL (range, 0.0 - 48.7 mL) postsurgery. All patients had performance status 0.
At 10 years, 60.6% of patients who received postoperative radiotherapy showed biochemical PFS compared with 41.1% of the wait-and-see patients; 70.3% of postoperative radiotherapy patients showed clinical PFS compared with 64.8% of the wait-and-see group.
No significant difference was found between the 2 groups in terms of overall survival (80.7% in postoperative radiotherapy patients vs 76.9% in wait-and-see patients). Regarding deaths resulting from prostate cancer, 5.4% of the patients died in the postoperative radiotherapy group, whereas 3.9% died in the wait-and-see group.
"When we look at baseline factors and biochemical PFS, all groups benefited. Patients with positive surgical margins and with seminal vesicle invasion benefit most. Those with negative surgical margins benefit less," Dr. Van Poppel said. "Even patients over 70 still have a clear biochemical PFS advantage. The clinical PFS results are similar, but those with negative surgical margins do not benefit any longer. For patients over 70 there is no benefit at all for having radiotherapy."
Dr. Van Poppel drew a comparison with the US-based Southwest Oncology Group (SWOG) trial, which looked at similar patients and outcomes. "In terms of overall survival in EORTC, there is a trend that patients who did not receive radiotherapy are doing at least as well as the others. Those with negative surgical margins and older [patients] do not benefit from radiotherapy. This is in conflict with the SWOG 8794 trial, which shows, with longer follow-up, that there is an advantage in postoperative radiotherapy patients for metastasis-free survival and overall survival — a difference that we, in this EORTC trial, were unable to confirm," said Dr. Van Poppel.
He provided an overview of patient differences between the 2 trials. In the SWOG trial, not many patients had performance status 0 (19.3%) compared with the EORTC trial (in which 94% of the patients had performance status 0). Twenty-two percent of the patients in the SWOG trial had 3 risk factors vs 12% of patients in the EORTC trial. More radiation was given in the SWOG trial (60 - 64 Gy compared with 60 Gy in the EORTC trial). PSA relapse was evident, with levels higher than 0.4 ng/mL after normalization in the SWOG. Any increase above the nadir was accepted as PSA failure in the EORTC trial.
"Regarding PFS, SWOG found that was 3.1 years in the wait-and-see arm and 6.12 years in the similar arm of the EORTC trial. So this means that in the observation arm, there were major differences, probably due to initial different prognostic factors in the 2 studies," Dr. Van Poppel said. "The same holds for distant metastasis-free survival, with 61% in the wait-and-see SWOG patients and 71.3% in wait-and-see EORTC patients; and also 10-year overall survival [66% in the wait-and-see SWOG patients and 80.7% in the wait-and-see EORTC patients]." Dr. Van Poppel suggested that worse patient prognosis in the SWOG study may account for this finding.
Freddie Hamdy, MD, chairman of the Scientific Congress Office and Nuffield Professor of Surgery at the University of Oxford in the United Kingdom, said, "The European Association of Urology was delighted to offer the opportunity for this important study to be highlighted at our annual congress. It demonstrates the ability of the European urological community to conduct key clinical trials, which are likely to change practice worldwide."
He continued: "In this case, the benefits of immediate postoperative radiotherapy remain uncertain in the absence of overall survival advantages in the EORTC study compared to the SWOG trial, and further research is warranted. The results will guide decision making when offering patients treatment options, and allow men to make informed choices, weighing risks against potential benefits when faced with difficult situations in managing prostate cancer."
Dr. Van Poppel and Dr. Hamdy have disclosed no relevant financial relationships.
European Association of Urology (EAU) 26th Annual Congress. Presented March 22, 2011.
Hein Van Poppel, MD, urologist from University Hospitals Leuven, Belgium, presented the 10-year follow-up results for the first time here at the European Association of Urology 26th Annual Congress. The data were the results of a longer-term follow-up to the 5-year analysis presented in 2005.
"We've shown that, after 5 years in a former analysis, there was a definite advantage for patients with immediate adjuvant radiotherapy with respect to the biochemical progression-free survival [PFS] and local relapses. We did not show an advantage for metastasis-free survival or overall survival," reported Dr. Van Poppel.
After 2005's 5-year analysis, this year's study presents new, longer-term findings that confirm the 5-year results. "The effects of an older median age in the 2 groups and the impact this has on [PFS] have been thoroughly examined," said Dr. Van Poppel.
"We know that when these patients had immediate postoperative radiotherapy, they do better, and had a longer biochemical [PFS] and clinical [PFS], especially in the case of positive surgical margins and extension of disease to the seminal vesicles. This is a very important message to the urological community," he added.
The EORTC study involved 1005 patients enrolled between 1992 and 2001, and the first 5-year analysis showing a significant difference in clinical and biochemical PFS was published in The Lancet (Bolla et al. 2005). The median follow-up is now 10.6 years. Patients were eligible if they had cT1-3N0M0 tumors treated with radical prostatectomy with adverse postoperative features of extracapsular extension, positive margins, or seminal vesicle invasion.
After surgery, patients either continued under wait-and-see management or received immediate postoperative radiotherapy of 60 Gy delivered over the course of 6 weeks. Groups were well balanced, with an average age of 65 years and median prostate-specific antigen (PSA) levels of 12.4 ng/mL (range, 0.3 - 159.4 mL) presurgery and 0.2 ng/mL (range, 0.0 - 48.7 mL) postsurgery. All patients had performance status 0.
At 10 years, 60.6% of patients who received postoperative radiotherapy showed biochemical PFS compared with 41.1% of the wait-and-see patients; 70.3% of postoperative radiotherapy patients showed clinical PFS compared with 64.8% of the wait-and-see group.
No significant difference was found between the 2 groups in terms of overall survival (80.7% in postoperative radiotherapy patients vs 76.9% in wait-and-see patients). Regarding deaths resulting from prostate cancer, 5.4% of the patients died in the postoperative radiotherapy group, whereas 3.9% died in the wait-and-see group.
"When we look at baseline factors and biochemical PFS, all groups benefited. Patients with positive surgical margins and with seminal vesicle invasion benefit most. Those with negative surgical margins benefit less," Dr. Van Poppel said. "Even patients over 70 still have a clear biochemical PFS advantage. The clinical PFS results are similar, but those with negative surgical margins do not benefit any longer. For patients over 70 there is no benefit at all for having radiotherapy."
Dr. Van Poppel drew a comparison with the US-based Southwest Oncology Group (SWOG) trial, which looked at similar patients and outcomes. "In terms of overall survival in EORTC, there is a trend that patients who did not receive radiotherapy are doing at least as well as the others. Those with negative surgical margins and older [patients] do not benefit from radiotherapy. This is in conflict with the SWOG 8794 trial, which shows, with longer follow-up, that there is an advantage in postoperative radiotherapy patients for metastasis-free survival and overall survival — a difference that we, in this EORTC trial, were unable to confirm," said Dr. Van Poppel.
He provided an overview of patient differences between the 2 trials. In the SWOG trial, not many patients had performance status 0 (19.3%) compared with the EORTC trial (in which 94% of the patients had performance status 0). Twenty-two percent of the patients in the SWOG trial had 3 risk factors vs 12% of patients in the EORTC trial. More radiation was given in the SWOG trial (60 - 64 Gy compared with 60 Gy in the EORTC trial). PSA relapse was evident, with levels higher than 0.4 ng/mL after normalization in the SWOG. Any increase above the nadir was accepted as PSA failure in the EORTC trial.
"Regarding PFS, SWOG found that was 3.1 years in the wait-and-see arm and 6.12 years in the similar arm of the EORTC trial. So this means that in the observation arm, there were major differences, probably due to initial different prognostic factors in the 2 studies," Dr. Van Poppel said. "The same holds for distant metastasis-free survival, with 61% in the wait-and-see SWOG patients and 71.3% in wait-and-see EORTC patients; and also 10-year overall survival [66% in the wait-and-see SWOG patients and 80.7% in the wait-and-see EORTC patients]." Dr. Van Poppel suggested that worse patient prognosis in the SWOG study may account for this finding.
Freddie Hamdy, MD, chairman of the Scientific Congress Office and Nuffield Professor of Surgery at the University of Oxford in the United Kingdom, said, "The European Association of Urology was delighted to offer the opportunity for this important study to be highlighted at our annual congress. It demonstrates the ability of the European urological community to conduct key clinical trials, which are likely to change practice worldwide."
He continued: "In this case, the benefits of immediate postoperative radiotherapy remain uncertain in the absence of overall survival advantages in the EORTC study compared to the SWOG trial, and further research is warranted. The results will guide decision making when offering patients treatment options, and allow men to make informed choices, weighing risks against potential benefits when faced with difficult situations in managing prostate cancer."
Dr. Van Poppel and Dr. Hamdy have disclosed no relevant financial relationships.
European Association of Urology (EAU) 26th Annual Congress. Presented March 22, 2011.
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