PR seems more effective against high-risk prostate cancer
Traditionally, radical prostatectomy (RP) in patients with high-risk prostate cancer has been considered less effective than external radiation therapy (EBRT) combined with androgen deprivation therapy. Emerging data over the past decade has demonstrated that PR with adjuvant or salvage therapy can be as effective as EBRT combined with androgen deprivation therapy.
In a study by Chierigo et al,1 the authors assessed the roles of RA and EBRT in cancer-specific mortality (CSM) difference in men with high-risk prostate cancer in the Surveillance, Epidemiology, and End Results (SEER). The authors hypothesized that there is no difference in CSM between RP and EBRT.
It is important to understand the different definitions of high-risk prostate cancer. The National Comprehensive Cancer Network (NCCN) definition includes either Gleason (GS) scores of 8-10 (level group 4-5) or prostate-specific antigen (PSA) levels greater than 20 ng/mL or clinical stage of at least T3. They then subdivided the high-risk prostate cancer cohort based on the Johns Hopkins classification into Johns Hopkins High-Risk (JH-HR) groups (cT3a or Level 4 group or PSA>20 ng/mL) and very high risk (JH-VHR) groups (cT3b-cT4 and or primary Gleason pattern 5 and or 2-3 HR features and or≥5 positive biopsy cores with grade 4 group).
In the SEER database, CSM was defined as deaths attributable to prostate cancer, as recorded on death certificates. Conversely, mortality from other causes was defined as deaths attributable to causes other than prostate cancer. In the SEER database (2010-2016), the authors identified all patients treated with RP or EBRT. The primary endpoint of this analysis was whether there were differences in CSM between PR and EBRT across the entire NCCN HR patient cohort, and whether differences in survival, based on treatment, existed within the JH-HR and JH-VHR subgroups. .
Of the 24,407 NCCN patients with high-risk prostate cancer, 9,823 (40%) underwent RA and 14,584 (60%) received EBRT. When divided into subgroups, 10,300 (42%) were classified as JH-HR and 14,107 (58%) were JH-VHR.
Among JH-HR patients, 4863 (47%) were treated with RP and 5437 (53%) with EBRT. Among JH-VHR patients, 4960 (35%) were treated with RP and 9147 (65%) with EBRT. Patients receiving brachytherapy, alone or in combination, were excluded.
Among the core cohort, EBRT patients were older (median age, 71 vs. 64 years), had higher PSA values (median, 13 vs. 8 ng/mL), and had higher clinical T and N stages. In addition, 5-year mortality rates from other causes were higher in the EBRT group than in the PR group (12% versus 3.4%).
The authors used propensity score matching (PSM) for the entire NCCN high-risk patient cohort to account for variation in baseline characteristics. PSM resulted in 2 equal groups of 7363 PR patients and 7363 EBRT patients, with no significant residual differences in age, PSA, GS biopsy, and clinical stages T and N. Median follow-up times for event-free patients were 41 months and 35 months for PR and EBRT, respectively. The rates of MSC at 5 years follow-up were 2.3% (95% CI, 1.9-2.9) for PsA and 4.1% (95% CI, 3.4-4, 8) for EBRT (P<.01 this resulted in a multivariate hazard ratio of competing risks ci>P<.001 in favor of rp. additionally the jh-vhr group was an independent predictor higher csm>P<.001 compared to the jh-hr group.>
After applying the PSM to the JH-VHR cohort, 2 equally sized groups of 4020 RP and 4020 EBRT were identified, with no statistically significant residual differences in age, PSA, GS biopsy, or clinical stages T and N The 5-year MSC rates were 3.5% for RP and 6.0% for EBRT (PP<.01 in favor of rp.>
Similarly, for the JH-HR cohort, matched groups of 3207 RP and 3207 EBRT were identified, with no statistically significant residual differences in age, PSA, GS biopsy, and clinical stages T and N. The rates of CSM at 5 years of follow-up were 0.7% for PR and 1.2% for EBRT, with a statistically non-significant multivariate multivariate hazard ratio of 0.7 (P=0.2).
High-risk prostate cancer requires multimodal treatment discussion and planning, regardless of the primary treatment used initially. In clinical practice, androgen deprivation therapy is used for virtually all patients receiving EBRT for high-risk prostate cancer. However, this information (i.e. percentage treated and dose and duration of androgen suppression therapy) is not available in this dataset. Similarly, 50% or more of post-RP high-risk patients will require adjuvant or salvage therapy (EBRT or androgen deprivation), but this information is also not available in the dataset. used for this analysis. Additionally, this population-based dataset does not provide information on comorbidities and other factors that lead to the selection of one treatment over another. PSM was used to account for the fact that the EBRT cohort was older and had a higher PSA level and higher stage; however, it cannot account for all unmeasured confounders. Despite several limitations, this type of analysis may be our best source of data regarding the comparative effectiveness of various treatment modalities for high-risk prostate cancer until ongoing randomized controlled trials are completed.
Several important points can be drawn from this analysis of a large population-based dataset of high-risk prostate cancer patients, which is then analyzed as the JH-HR and JH-VHR cohorts. JH subclassification into HR and VHR appears to be a robust prognostic variable for CSM. CSM was lower for PR-treated patients, compared to EBRT, in the entire NCCN cohort and in the JH-VHR prostate cancer patient subgroup, but not in the JH-HR subgroup. This may be because the event rate (i.e. death) was quite low in the JH-HR prostate cancer group. Interestingly, in the JH-HR group, the 5-year MSC rate was only 0.7% for RP and 1.2% for EBRT. It is very possible that high-risk prostate cancer detected by PSA portends a more favorable outlook compared to the pre-PSA era, regardless of the type of primary treatment used. These data may be useful in counseling patients about primary RP or EBRT and the risk of death after definitive treatment for high-risk prostate cancer.
1. Chierigo F, Wenzel M, Würnschimmel C, et al. Survival after radical prostatectomy versus radiotherapy in high-risk and very high-risk prostate cancer. J Urol. 2022;207(2):375-384. doi:10.1097/JU.0000000000002250