EURURO Vol. 71 No. 5

772 844

evaluation. However, our overall outcomes are consistent
with previously reported series as noted above, suggesting
an element of generalizability to our results. Not all patients
received standard of care treatment. Specifically, the
National Comprehensive Cancer Network and European
Association of Urology/European Society for Radiotherapy &
Oncology/International Society for Geriatric Oncology
guidelines suggest a multimodal approach (including either
ART or SRT) for patients with high-risk CaP—a suggestion
supported by a recent large surgical series in patients with
high-risk CaP . While only 12.4% of patients received
ART, 80% of the remaining RP patients with BCR but no DM
at the time ultimately received SRT, and therefore a
majority of surgical patients did receive appropriate
multimodal therapy . When analysis was restricted
to only these surgical patients, and comparisons were made
to EBRT patients with high-dose RT and long duration ADT
and EBRT + BT patients with >6 mo of ADT, our results were
essentially unchanged, suggesting our results are not only
generalizable to de facto clinical practice (which may or
may not be standard of care), but to standard of care
practice as well. Additionally, proportionately greater
numbers of RP patients received standard of care per this
definition than EBRT or EBRT + BT patients (84.1% vs 48.3%
and 60.9%, respectively). However, earlier initiation of SRT
has been shown to improve outcomes, particularly for
patients with high GS disease, and thus it is possible that
earlier SRT might have improved outcomes . The
numbers of patients analyzable for clinical outcomes at
10 yr of follow-up were fairly limited across cohorts, and
thus our Cox analyses using data from 10 yr of follow-up, as
well as exact estimates by Kaplan-Meier analysis at 10 yr,
must be interpreted judiciously. We did not account or
adjust for comorbidities, which have previously been
shown to be unbalanced between EBRT and RP cohorts
a uniform comorbidity index was not available for most
patients, and we did not feel it was appropriate to perform a
comorbidity-adjusted analysis on a limited subset. Howev-
er, our competing risk analysis for PCSM did not yield
different findings from our main analyses. Because not all
biopsies were performed uniformly and were done over a
broad time period, we did not include percentage of core
involvement with bGS 9–10 CaP as a variable of interest. At
least one prior study has suggested that burden of bGS 9–10
might be associated with outcomes . It is possible that
an imbalance of percentage involvement between the arms
might explain the results, though again, outcomes for each
cohort were consistent with prior results. A central
pathology review was not possible.
Finally, while our median follow-up of 4.6 yr was enough
to capture a fair number of systemic failure events, this
follow-up period may still be too short to capture mortality
outcomes. Additionally, some may contend that the long
duration of ADT, particularly in the EBRT cohort, may simply
be delaying, rather than truly preventing, the emergence of
metastatic disease. This is certainly possible, but the median
follow-up of the EBRT + BT cohort, which had a median ADT
duration of only 8 mo, was 6.5 yr, versus 4.9 yr for the RP
cohort. Further, as discussed above, ADT has never
demonstrated a benefit when combined with RP; a
contention that ADT only delays metastases does not
address the superior outcomes of EBRT + ADT over EBRT
alone and the lack of superior outcomes of RP + ADT over RP
alone, and delaying metastatic disease is in and of itself an
important endpoint.
5. Conclusions
In conclusion, our data suggest that the RP and EBRT-based
treatments provide equivalent CSS and OS for patients with
bGS 9–10 CaP, with extremely dose-escalated RT (as
exemplified here by EBRT + BT) providing the best systemic
control. It is important to note that 55% of patients who
underwent upfront RP ultimately received ART or SRT. This
should be emphasized when specialists partake in shared-
decision making with these patients. These data are
hypothesis-generating in suggesting that optimal outcomes
in patients with GS 9–10 CaP require a combination of local
control (offered by extremely-dose escalated RT) and
systemic therapy (offered by upfront ADT). Alternative
strategies, perhaps including some form of systemic
therapy with RP, may offer comparable outcomes.
Author contributions: Amar U. Kishan had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Kishan, Kupelian, King.
Acquisition of data: Kishan, Shaikh, Reiter, Said, Raghavan, Nickols,
Aronson, Sadeghi, Demanes, Horwitz.
Analysis and interpretation of data: Kishan, King.
Drafting of the manuscript: Kishan, King.
Critical revision of the manuscript for important intellectual content:
Kishan, Shaikh, Wang, Reiter, Said, Raghavan, Nickols, Aronson, Sadeghi,
Kamrava, Demanes, Steinbeg, Horwitz, Kupelian, King.
Statistical analysis: Kishan, Wang, King.
Obtaining funding: None.
Administrative, technical, or material support: King, Kupelian, Steinberg,
Demanes, Horwitz.
Supervision: King.
Other: None.
Financial disclosures: Amar U. Kishan certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
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