EURURO Vol. 72 No. 3

352 476

Platinum Priority – Editorial
Referring to the article published on pp. 345–351 of this issue
Local Therapy for Disseminated Prostate Cancer:
Improved Outcomes or Biased Confounders?
Chad A. Reichard, Brian F. Chapin
University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Enthusiasm for radical treatment with curative intent in the
setting of prostate cancer (PC) at high risk of dissemination
and/or metastatic disease (oligometastatic or otherwise)
has been kindled by several observational epidemiologic
studies and small pilot studies These studies have
been spurred by preclinical observations (reseeding and
persistence of viable tumor despite systemic therapy) and
the survival benefit of cytoreductive in other metastatic
urologic cancers.
In this issue of European Urology, Sooriakumaran et al
present robust epidemiologic data from the PCBaSe Sweden
that adds to the growing hypothesis-generating literature
outlining the potential PC-specific mortality (PCSM) ben-
efits of local therapy in men at high risk of disseminated PC.
There is a reported >25% absolute difference in PCSM
between radically treated and non-radically treated
matched groups. Whether this same benefit is borne out
in four ongoing prospective randomized trials remains to be
seen. Thus, while it is tempting to change practice patterns
or use this evidence as rationale to ‘‘push the envelope’’ or
‘‘do everything possible’’ for younger, healthier patients, it is
important to recognize several limitations of registry data in
answering these questions and to understand that it is
unlikely that all patients will benefit from local therapy.
The authors discuss difficulty in matching patients
owing to disparities between the ‘‘average’’ patient receiv-
ing radical therapy and the ‘‘average’’ patient who received
androgen deprivation therapy (ADT) alone (the latter
having significantly worse prognostic factors). Drawing
from 17 602 patients receiving ADT alone, they were only
able to match 575 out of 750 radical therapy comparators.
Notably, the matched ADT group still had a larger
proportion of N1 and M1 patients, despite inclusion in
the matched radical treatment cohort of 20/26 N1 patients
and all ten patients with metastatic disease from the
unmatched radical treatment cohort. Thus, these study
groups are highly susceptible to both known and unknown
confounders and therefore significant selection bias.
On the basis of the reported initial identification criterion
of prostate-specific antigen >50 ng/ml, only 1.3% of the
radical treatment cohort had M1 disease, compared to 40%
in the ADT cohort. The authors acknowledge this heteroge-
neity with potential for predominance of large, locally
advanced tumors, but also oligometastatic disease as well.
The potential presence of occult metastatic disease may
account for the fact that any reported nodal or metastasis
inequalities in the main matched cohort did not appear to
significantly affect the survival benefit findings. These
points highlight the importance of stringent categorization
of these patients to minimize factors that impair reliable
application of the study findings to practical clinical
decision-making. However, categorization on the basis of
imaging-based findings alone seems somewhat elementa-
ry; rather, we should be focusing on classifying subsets on
the basis of tumor biology and linking these subsets to
specific therapies.
The authors importantly highlight the problematic
absence of information on secondary treatment in the
radical therapy group as a potential source of confounding,
underscoring the importance of standardization of subse-
quent therapies and/or meticulous data collection in this
regard for ongoing trials. Moreover, there is rapid ongoing
evolution of the development and implementation of
survival-prolonging treatments and prognostic factors
available at
journal homepage:
DOI of original article: .
* Corresponding author. Department of Urology, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030,
USA. Tel. +1 713 7923250; Fax: +1 713 7923474.
E-mail address: (B.F. Chapin).
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.