The optimal management for patients with high-risk prostate cancer remains controversial. An increasing proportion of high-risk patients are treated with combined radiation and hormonal therapy, in light of evidence from randomized controlled trials demonstrating an advantage over radiation alone. In 1997, Bolla et al. reported on this issue in 415 men with clinical stage T3 or poorly-differentiated clinical stage T1–T2.6
At 5 years, overall survival was 62% with radiation monotherapy, versus 79% for radiation therapy with hormonal therapy (p<0.001). Subsequently, D’Amico et al. validated these findings in 206 patients with clinically localized intermediate to high-risk prostate cancer randomized to EBRT alone versus EBRT plus six months of hormonal therapy.7
Prostate cancer-specific mortality was significantly higher with EBRT alone, and the 5-year overall survival rates were 78% and 88% in the EBRT and combination therapy groups, respectively.
Today however many men wish to avoid the side effects associated with long-term hormonal therapy, including osteopenia, impaired cognitive function, hot flashes, impotence, loss of libido, gynecomastia and potential increased risk of cardiovascular events.9,10
For this reason for many patients, especially young men, the alternative option of primary surgical therapy for high-risk patients is attractive.
Several independent studies have examined the results of radical prostatectomy among men meeting one of the three original D’Amico high-risk criteria. For example, our group has previously reported on the outcomes after RP among 62 men with clinical stage T3 disease, who were diagnosed between 1987 and 2003.11
At a median follow-up of 10.3 years, 50% had biochemical progression, 21% had metastases and 13% died from prostate cancer. The corresponding 15-year metastasis-free and cancer-specific survival rates were 73% and 84%, respectively.
Magheli et al. specifically examined the results of 265 men with a preoperative PSA level >20 ng/ml who underwent radical prostatectomy at our institution.12
Of these men, 50 (19%) had anterior tumors. The 5- and 10-year biochemical progression-free survival rates were 47% and 33%, respectively. Of note, patients with anteriorly-located tumors were significantly less likely to experience biochemical progression.
With respect to high-grade disease, Bastian et al. previously reported on the outcomes of radical prostatectomy in 369 men with a biopsy Gleason score of 8 to 10 from the Johns Hopkins and SEARCH databases.13
Overall, they reported organ-confined disease with negative surgical margins in 21% and 41%, with 10-year progression free survival rates were 27% (18–36%) and 28% (18–36%) in the two populations, respectively. The metastases-free and cancer-specific survival rates were not reported in this study.
Boorjian et al. reported on 1513 men with D’Amico high-risk disease who underwent radical prostatectomy at the Mayo Clinic.14
The 10-year biochemical progression-free, systemic progression-free, and cancer-specific survival rates were 55%, 89%, and 95%, respectively. Loeb et al. similarly reported the outcomes of radical prostatectomy in 288 men with clinical stage T3 or high-risk T2b (PSA >15 ng/ml or Gleason 8 to 10) prostate cancer.15
In this series, the actuarial progression-free survival rate was 35% and cancer-specific survival rate was 88% at 10 years.
Herein, we expand upon these findings to report on the outcomes of all men with high-risk prostate cancer treated by the same surgeon (PCW). Although only one-third of this cohort had organ-confined disease in the radical prostatectomy specimen, 68% had no evidence of biochemical recurrence at 10 years. Moreover, the metastasis-free and cancer-specific survival rates were impressive at 84% and 92%, respectively. Finally, the majority of men avoided hormonal therapy, with its significant associated side effects.
Several limitations of our study deserve mention. First, our population represents a carefully selected surgical population, who may not be representative of all men with high-risk prostate cancer. In addition, all men were treated by a single high-volume surgeon, and several studies have shown a relationship between surgeon experience with treatment-related outcomes.16
On the other hand, we chose to focus on a single-surgeon experience to ensure that all patients were managed using the same follow-up protocol. Of note, very few men in our series received postoperative radiation therapy. Accumulating evidence from randomized trials suggests a survival advantage associated with adjuvant radiation therapy in specific pathologic subgroups.17–19
Additional study is therefore warranted to compare the long-term outcomes between adjuvant and early salvage radiation therapy in this setting.
Another limitation of our study is the relatively small sample size, limiting the power to define subgroups with varying risk of recurrence, metastasis or death. However, our rates of PFS, MFS and CSS, as well as the occurrence of pathological stage ≥T3 and lymph node metastases were comparable to those reported at the Mayo Clinic.14
Because men with multiple high risk features are infrequently managed at our institution with surgery alone, only 6% of the men in our series had multiple high-risk features. Prior studies have shown worse treatment outcomes among men with multiple high-risk features.20
Nevertheless, it is unlikely that our results represent a high degree of selection for better prognosis patients given the similarity of our outcomes to those of high-risk patients reported by Boorjian.14
Another limitation is that the D’Amico classification is one of many criteria for high-risk prostate cancer,21
and some prior studies have shown heterogeneity in outcomes depending upon the definition of high-risk disease.22
Thus, additional study of long-term radical prostatectomy outcomes is warranted using alternate criteria.
In addition, our Kaplan-Meier analyses suggested worse outcomes for clinical stage T2b compared to T2c/T3. However, we believe this is an artifact of the definition for high- risk prostate cancer, in that men with T2b tumors must have either a biopsy Gleason score of 8–10 or PSA >20 ng/ml to be considered high risk. Since the majority of our patients had only one high risk characteristic, a comparison of men with lower versus higher clinical stage is necessarily a comparison of Gleason 8–10 vs. <8, or PSA >20 vs. ≤20 ng/ml.
Finally, 11 men treated during the study period did not undergo radical prostatectomy due to a finding of positive lymph nodes during staging lymphadenectomy or intraoperatively. Thus, it is unknown what their results would have been had they undergone radical prostatectomy. However, we did perform separate “intent-to-treat” Cox proportional hazards models including these men and the results did not change.