Download The age old question: who benefits from prostate cancer treatment?

Editor’s Choice
The age old question: who benefits from prostate
cancer treatment?
Widespread PSA-based screening has dramatically altered the
profile of newly diagnosed prostate cancer in many countries.
Although screening effectively decreases the rates of metastatic
disease and prostate cancer death [1], the increasing
proportion of low-risk disease necessitates a critical
assessment of the need for aggressive therapy.
Active surveillance and watchful waiting are potential
alternatives to delay or avoid the need for treatment in
carefully selected patients. The key issue is determining which
patients are appropriate for conservative management.
Although these approaches are often targeted toward elderly
men, such men are more likely to be diagnosed with high-risk
disease. A recent study by Scosyrev et al. [2] raised concern
about excess prostate cancer mortality attributable to
under-treatment in the elderly.
Overall, there is very little Level 1 evidence to guide prostate
cancer treatment selection. One such trial, the Swedish
Prostate Cancer Group 4 (SPCG-4), showed that radical
prostatectomy significantly improved survival compared with
watchful waiting [3]; however, that study examined a primarily
clinically detected population from the 1990s. Subsequently,
the Prostate Cancer Intervention versus Observation Trial
(PIVOT) randomized US male veterans diagnosed with
prostate cancer from 1994 to 2002 to radical prostatectomy vs
observation [4]. At 10 years, they reported no significant
difference in overall survival between the two arms in the
intent-to-treat analysis (hazard ratio 0.88; 95% CI 0.71–1.08, P
= 0.22). However, that study was smaller than anticipated
owing to difficulty with recruitment and there was a high rate
of crossovers between the intervention and observation arms.
Per-protocol analysis was not reported for PIVOT and the
prostate cancer landscape has continued to change in the past
decade, raising unanswered questions over what the results
would be if we compared contemporary men who were
actually treated to those who were not.
This is the knowledge gap addressed by Aizer et al. [5] who
used Surveillance, Epidemiology and End Results (SEER) data
for 27 969 US men diagnosed with low-risk prostate cancer
from 2004 to 2007. Overall, 67.1% of these men received
radical prostatectomy or radiation therapy, while >30%
underwent active surveillance or watchful waiting. Using
© 2013 The Author
4 BJU International © 2013 BJU International
competing risks regression, they showed that both age and
non-curative treatment were associated with a significantly
higher short-term prostate cancer-specific mortality. These
results should be interpreted with caution, however, since
they comprise observational data with great potential for
confounding. Interestingly, at a short median follow-up of
only 2.75 years, 5.4% of these men with presumed low-risk
disease died from prostate cancer. Recently, there has been
debate over whether Gleason 6 disease should really be
considered a cancer [6], but these data highlight the
limitations of current clinical staging, such that even
presumed low-risk disease may be understaged. The authors
suggest that use of a more extended biopsy scheme before
active surveillance might reduce the risk of early progression
due to undersampling. MRI represents another potential
non-invasive treatment method to improve clinical staging
and patient selection for active surveillance in the future [7].
Conflict of Interest
None declared.
Stacy Loeb
Department of Urology, New York University, New York,
NY, USA
References
1
2
3
4
5
6
7
Schroder FH, Hugosson J, Roobol MJ et al. Prostate-cancer mortality at
11 years of follow-up. N Engl J Med 2012; 366: 981–90
Scosyrev E, Messing EM, Mohile S et al. Prostate cancer in the elderly:
frequency of advanced disease at presentation and disease-specific
mortality. Cancer 2012; 118: 3062–70
Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy
versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364:
1708–17
Wilt TJ, Brawer MK, Jones KM et al. Radical prostatectomy versus
observation for localized prostate cancer. N Engl J Med 2012; 367: 203–12
Aizer AA, Chen MH, Hattangadi J, D’Amico AV. Initial management of
prostate-specific-antigen-detected, low-risk prostate cancer and the risk of
death from prostate cancer. BJU Int 2014; 113: 43–50
Carter HB, Partin AW, Walsh PC et al. Gleason score 6 adenocarcinoma:
should it be labeled as cancer? J Clin Oncol 2012; 30: 4294–6
Vargas HA, Akin O, Afaq A et al. Magnetic Resonance Imaging for
Predicting Prostate Biopsy Findings in Patients Considered for Active
Surveillance of Clinically Low Risk Prostate Cancer. J Urol 2012; 188:
1732–8