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3.3. Functional outcomes: classic complications
The complications of PCa treatment that are best charac-
terized and most frequently discussed are urinary inconti-
nence and erectile dysfunction. The SPCG-4 trial
demonstrated that radical prostatectomy increased rates
of these complications but decreased rates of urinary
obstruction in comparison to watchful waiting . Owing
to the field effects of radiotherapy, both EBRT and
brachytherapy significantly affect HRQoL bowel and rectal
domains . While most bowel effects are transient, a
proportion persist for many years after treatment . Typ-
ically, bowel symptoms are worse for patients undergoing
EBRT than those receiving brachytherapy
As with global HRQoL, three randomized controlled trials
compared functional PROs for those treated with surgery and
radiotherapy. In the ProtecT study, surgery was associated
with higher rates of urinary incontinence and erectile
dysfunction, while radiotherapy had greater obstructive
urinary symptoms and bowel symptoms . Differences
in urinary incontinence and erectile dysfunction between
treatment modalities diminished with longer follow-up ,
in keeping with the observational findings of the Prostate
Cancer Outcomes Study Lennernas et al found no
significant differences in urinary urgency, urinary inconti-
nence, erectile dysfunction, sexual interest, or rectal bleeding
between men treated with surgery and radiotherapy. They
noted significant worsening of urinary incontinence, erectile
dysfunction, and sexual interest over time in both groups.
Gilberti et al found that men treated with brachytherapy
had worse urinary function at 6 and 12 mo, worse bowel
function at 6 mo, and better erectile function at 6 mo
compared to those treated surgically. However, therewere no
significant differences in any functional outcome at 5 yr.
There is a wealth of observational data examining
functional PROs. Most notably, the Prostate Cancer Out-
comes Study recruited 3533 men from six Surveillance,
Epidemiology and End Results registries , of whom
1655 patients with localized disease received surgery or
radiotherapy treatment within 1 yr of diagnosis and
completed follow-up surveys beyond 2 yr. At 2 and 5 yr
following treatment, men receiving surgery were more
likely to report urinary incontinence and erectile dysfunc-
tion, while those receiving radiotherapy were more likely to
report bowel urgency and bother due to bowel symptoms
. By 15 yr, all differences became nonsignificant, except
for bowel symptoms, which remained higher among men
treated with radiotherapy . In addition, by 15 yr, most
men had developed erectile dysfunction . More recent
observational data have corroborated these findings among
men treated with modern treatments, albeit with short
follow-up (2 yr and 3 yr) .
Despite these data, a recent systematic review concluded
there were insufficient data on symptomatic and QoL
outcomes following localized PCa treatment to provide
meaningful treatment guidance . In part, this is because
of the use of differing assessment measures. A recent Delphi
consensus among patients, urologists, and radiation oncol-
ogists sought to standardize the reporting of outcomes
following localized PCa treatment . They advocated use
of the Expanded Prostate Cancer Index Composite (EPIC-26)
for assessment of PROs, although numerous others were
also endorsed. Data collection for 10 yr following treatment
was recommended.
3.4. Functional outcomes: novel complications
Complications related to PCa treatment may necessitate
interventions including urologic procedures, rectal-anal
procedures, and major surgery. These complications, includ-
ing genitourinary or gastrointestinal bleeding, infection, and
urinary obstruction, may also require planned or unplanned
hospitalization In addition, a further risk following
radiotherapy is treatment-induced secondary malignancy.
In a large population-based cohort of patients treated for
nonmetastatic PCa in Ontario, Canada, radiotherapy treat-
ment was associated with higher risks of hospitalization,
rectal-anal procedures, major surgeries, and secondary
cancers, but lower risk of minimally invasive urologic
procedures, when compared to surgery After propen-
sity score matching to account for baseline differences,
patients receiving radiotherapy had greater long-term risk
of all of these outcomes Validation in an independent
cohort of patients from the USA showed that these
complications frequently recur (mean 2.6 per patient)
and continue for years following treatment . Using
the same patient cohort but different analysis methods,
Williams et al found no difference in treatment-
related hospitalizations, although there was greater cost
associated with treatment of patients who received
radiotherapy.
While the use of postoperative radiotherapy contributed
to higher complication rates, when taken on an intention-
to-treat basis, the initial decision to begin therapy with
surgery was associated with lower long-term risk of all
procedural interventions and hospitalizations .
Complications arising from radiotherapy, the end
result of which is chronic tissue ischemia have
a profoundly different prognosis than those arising
following surgery, which maintains the underlying tissue
integrity. Radiotherapy-associated complications are signif-
icantly more burdensome and often entail a much slower
recovery, with impaired long-term function Most
notably, urinary fistulae following prostate radiotherapy
often require urinary diversion and are associated with
significant morbidity
In the Ontario cohort, patients treated with radiotherapy
had a significantly higher risk of secondary cancers
(standardized incidence rate [SIR] 2.0, 95% CI 1.7–2.3), driven
by anexcess of secondary cancers inmen aged40–65yr at the
time of radiotherapy (SIR 3.5, 95% CI 2.3–4.7) This
finding has recently been supported by a meta-analysis
comprising 21 studies and up to 555 873 patients that
revealed a greater risk of in-field secondary malignancies
(bladder, rectal, and colorectal cancers) but not of out-of-field
malignancies among patients treated with radiotherapy,
although the absolute risk was small (0–1.4 cases per
100 patients treated)
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