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adjuvant treatment would be free from metastases at 10-yr
follow-up. To address this void, we hypothesized that while
postoperative RT might improve oncologic outcomes in
some patients, it may represent an overtreatment in others.
Our results support this hypothesis, as we found that
postoperative RT was associated with decreased CSM only
in men with more aggressive disease at RP. From a clinical
standpoint, our model may thus assist clinicians in the
identification of patients with a lower baseline risk of CSM,
who therefore, should be initially managed expectantly.
Conversely, men with a higher risk of CSM should be
considered for additional postoperative treatments such
as RT.
We recognize that our study is not devoid of limitations.
First, although we adjusted our analyses for potential
confounders, we cannot completely exclude an effect of
selection bias. The indication to administer RT or ADT was
not standardized, and varied according to the treating
physician and patient preferences. Randomized controlled
trials specifically designed to address the efficacy of
postoperative RT in the setting of PSA persistence are
needed to address this issue. Second,
>
40% of men not
receiving postoperative RT received ADT, which may
represent a confounding factor. Nonetheless, our predictive
model accounted for the effect of immediate postoperative
ADT. Third, the lack of a pathologic review might limit
the validity of our findings. Nonetheless, all patients
included in our study were evaluated by high-volume
dedicated uropathologists at two tertiary referral centers.
Fourth, the model predicting 10-yr CSM in men who did not
receive RT exhibited suboptimal calibration characteristics
at internal validation. This might be related to the relatively
small number of events among patients who did not receive
postoperative RT. Finally, the lack of data on PSA kinetics
after surgery precluded us to adjust our analyses for this
variable. However, our risk model to predict the 10-yr risk
of CSM is based on readily available variables to the
practicing clinician and should thereby assist in patient
counseling and postoperative management.
5.
Conclusions
Not all PCa patients with PSA persistence after RP have
universally poor oncologic outcomes. Increasing PSA levels
should be considered as predictors of mortality, exclusively
in men with a risk of CSM of
>
10% defined by pathologic
characteristics. Likewise, the benefits of postoperative RT on
survival are restricted to those men with adverse pathology,
indicating the opportunity for an individualized approach to
treatment in these patients.
Author contributions:
Alberto Briganti 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:
Briganti, Boorjian, Gandaglia.
Acquisition of data:
Gandaglia, Parker, Fossati, Bandini, Dell’Oglio, Suardi.
Analysis and interpretation of data:
Briganti, Gandaglia, Zaffuto.
Drafting of the manuscript:
Gandaglia, Briganti, Boorjian.
Critical revision of the manuscript for important intellectual content:
Briganti, Boorjian, Karnes, Montorsi.
Statistical analysis:
Gandaglia, Zaffuto.
Obtaining funding:
Montorsi, Boorjian.
Administrative, technical, or material support:
None.
Supervision:
Briganti, Boorjian, Karnes, Montorsi.
Other:
None.
Financial disclosures:
Alberto Briganti 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
http://dx.doi.org/10.1016/j. eururo.2017.06.001 .References
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