Download Longterm survival after radical prostatectomy versus externalbeam

Editorial
Long-Term Survival After Radical
Prostatectomy Versus External-Beam
Radiotherapy for Patients With High-Risk
Prostate Cancer1?
Jeffrey M. Holzbeierlein, MD
Radical prostatectomy remains the most commonly used therapy for the treatment of localized prostate cancer in the
US Surgical management accounts for a significant percentage of the 1.7 billion dollars spent each year in the treatment of
this disease. Recently, there has been a shift in technique from open radical prostatectomy to robotic prostatectomy,
although oncologic outcomes appear to be similar. Despite this evolution in technique, approximately 30% of patients
treated with radical prostatectomy will ultimately fail, the vast majority with biochemical recurrence as the first sign. The
majority of patients who recur are often those who present with high-risk cancer.
Numerous published studies have addressed the efficacy of radical prostatectomy for the treatment of high-risk prostate cancer. One such study was the retrospective review published by Bastian et al.2 This group evaluated a cohort of
high-risk patients, defined as Gleason sum 8-10 and treated with radical prostatectomy without adjuvant therapy. The
authors reported that only 25% of men remained without evidence of biochemical recurrence at 10 years. Furthermore, of
those patients with favorable pathologic findings, defined as organ-confined disease and negative surgical margins (which
only occurred in 21% of patients), less than 50% remained biochemically free of disease.2 Indeed, there has been recognition of the substantial failure rate of radical prostatectomy monotherapy in the treatment of high-risk prostate cancer.
This failure has led to several clinical trials including the current, ongoing, Cancer and Leukemia Group B (CALGB90,203) trial that is examining neoadjuvant chemotherapy and hormone therapy in an effort to improve outcomes in
patients with high-risk disease. With the publication of the Radiation Therapy Oncology Group (RTOG 85-31) study
and the European Organisation for Research and Treatment of Cancer (EORTC) study, both of which demonstrated a
survival advantage with the addition of androgen deprivation to external-beam radiation therapy, many have deferred to
this approach for patients with high-risk disease.3,4 This is despite the finding that only 11% of men remained disease free
at 10 years with radiation plus androgen deprivation in the RTOG study.5 The National Comprehensive Cancer Network
(NCCN) guidelines recommend either radical retropubic prostatectomy (RRP) or external-beam radiation therapy plus
external radiation therapy (EBRT þ XRT) for the treatment of high-risk prostate cancer patients. Thus, the question of
the optimal treatment approach for patients with high-risk prostate cancer remains an important issue that these authors
attempted to address.
In this article by Boorjian et al,1 the authors retrospectively examined 2 large databases of patients with high-risk
prostate cancer treated with either XRT or RRP in an effort to determine whether 1 treatment is superior to the other. The
authors used the NCCN definition for high-risk prostate cancer, which includes patients with Gleason sum 8-10, clinical
category T3 or greater, or prostate specific antigen (PSA) level of >20 ng/mL. The authors concluded that RRP is comparable to EBRT alone or in combination with androgen deprivation therapy (EBRT þ ADT) in risk of systemic progression. For prostate cancer-specific mortality, RRP and EBRT þ ADT appear equivalent with a trend toward worse
Corresponding author: Jeffrey M. Holzbeierlein, MD, Department of Urology, University of Kansas Hospital, 3901 Rainbow Blvd, Mail Stop 3016, Kansas City, KS
66160; Fax: (913) 588-7625; [email protected]
Department of Urology, University of Kansas Hospital, Kansas City, Kansas
See referenced original article on pages 2883-91, this issue.
DOI: 10.1002/cncr.25899, Received: November 23, 2010; Revised: December 8, 2010; Accepted: December 14, 2010, Published online January 24, 2011 in Wiley
Online Library (wileyonlinelibrary.com)
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High-Risk Prostate Cancer/Holzbeierlein
outcomes with EBRT alone; however, this was not statistically significant. Last, after attempting to statistically control factors such as comorbidities (measured by Charlson
comorbidity index), age, and other clinical factors, Boorjian et al reported an increased overall survival advantage
for patients treated with RRP compared with EBRT or
EBRT þ ADT.
Boorjian and colleagues1 should be commended for
a robust study with a large population of high-risk prostate cancer patients. Their article has several strengths
including their use of the NCCN definition for high-risk
prostate cancer. Many previous studies have had conflicting results due to differences in criteria used to define a
patient with ‘‘high-risk’’ prostate cancer. Thus, by using a
clear definition as reached by consensus in the NCCN
guidelines, the authors have provided a reasonable framework on which to compare different therapies and future
studies. Second, the datasets for both the radiation and
prostatectomy cohorts are large and have mature followup, an absolute necessity when looking at prostate cancer
outcomes. However, the nature of a retrospective chart
review lends itself to some inherent criticisms. These
weaknesses include variations in radiation delivery and
substandard doses in the earlier EBRT patients, differences in surgery versus radiation patient populations, and no
standardization of the radical prostatectomy (nerve-sparing vs wide-dissection) and lymph node dissection (limited vs extended).
Despite these limitations, there are several interesting observations that can be made. First, the Boorjian et al1 article demonstrates that RRP can be an
effective treatment for high-risk prostate cancer compared with EBRT þ ADT. However, what needs to be
emphasized is that rarely, as monotherapy, does RRP
result in a cure. In their study, more than 60% of men
treated with RRP received additional therapy, either
adjuvant or salvage. From this article, we cannot discern the indications for adjuvant therapy that were
used in 40% of patients, but one would presume this
was because of positive lymph nodes, positive surgical
margins, and/or failure of the prostate-specific antigen
(PSA) level to nadir at 6 weeks. Another observation
the authors made is that time to institution of ADT
was shorter in the radiation groups versus those in the
RRP group. However, there was a large difference in
the number of men who received additional ADT after
their initial treatment with more than 40% of men
receiving ADT after RRP versus only 16.6% of
patients receiving additional ADT after the initial treat-
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July 1, 2011
ment with EBRT and ADT. Unfortunately, for the
vast majority of men who undergo RRP with subsequent ADT, it is lifelong, rather than for a limited
time. This finding also appears to cast some doubt on
the theory that the decreased overall survival seen with
EBRT and EBRT þ ADT is due to ADT use. Instead,
as the authors have pointed out in their discussion, it
is possible that the difference really is due to the
patient populations being treated with radiation rather
than surgery, a difference which most surgeons would
conclude cannot be measured by a Charlson score
alone. Therefore, a reasonable conclusion is that there
may be no significant differences between EBRT þ
ADT and RRP for the treatment of high-risk prostate
cancer for any of the outcomes the Boorjian et al1
study measured. This conclusion may be the most important point, which is that RRP does provide an
effective treatment option for patients with high-risk
disease, although with the caveat that it rarely results
in ‘‘cure’’. Thus, it is important for clinicians to continue to explore multimodal options for the treatment
of high-risk prostate cancer.
Ultimately, what is needed is a prospective, randomized, controlled trial of high-risk prostate cancer that
evaluates RRP versus EBRT þ ADT in the setting of multimodal therapy. Furthermore, if equivalent, then the next
logical step would be to evaluate side effects and qualityof-life factors. What is not emphasized in the Boorjian1
article, and is hard to quantify, are some of the other benefits of RRP. These include local control of the cancer,
which leads to decreases in long-term complications such
as recurrent hematuria, bladder outlet obstruction, ureteral obstruction, and pain that may be seen in advanced
disease when the prostate is left in place. In addition, the
ability of pathologic data to help direct additional therapy
is also important. With data from the Messing trial6 demonstrating an advantage in survival for long-term ADT in
lymph node-positive patients and data from the Southwest Oncology Group (SWOG 8794)7 for the use of adjuvant radiation therapy in high-risk patients, good
pathologic data are extremely important in helping to
direct patients toward appropriate therapy. In conclusion,
the Boorjian et al study has demonstrated that patients
treated with radical prostatectomy have similar, if not better, outcomes than those treated with EBRT, and, therefore, RRP should be a valid option in the management of
high-risk prostate cancer. Future results of neoadjuvant
trials with RRP are crucial to improving outcomes in
patients with high-risk prostate cancer, and once
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completed, it will be important to perform prospective
randomized trials to more accurately determine the best
treatment option for this group of patients.
4.
CONFLICT OF INTEREST DISCLOSURES
The author made no disclosures.
5.
REFERENCES
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2. Bastian PJ, Gonzalgo ML, Aronson WJ, et al. Clinical and
pathologic outcome after radical prostatectomy for prostate
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