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"What Are the Side Effects of Your
Treatment, Doctor?" - Second Edition
(March 2008)
A patient's choice
among treatment options is increasingly determined by consideration of
unwanted side effects. Lead off statements from two recent articles on
heath-related quality of life (QOL) issues underscore this point. One
stated, "Given the lack of unequivocal survival data clearly favoring
one treatment over another for localized prostate cancer, patients
strongly consider quality-of-life effects when choosing treatment for
this common malignancy" - Dr. David Penson in "Quality of Life After
Therapy for Localized Prostate Cancer" in The Cancer Journal,
Sep/Oct, 2007. And, another - "The primary treatments for clinically
localized cancer confer equivalent cancer control, but disparate side
effects" - Dr. Litwin, in "Quality of life after surgery, external beam
irradiation, or brachytherapy for early stage prostate cancer, Cancer,
June 1, 2007. This putative equivalence of outcome among the three major
modes of primary therapy highlights the need for an accurate assessment
of therapy related urinary, bowel, and sexual dysfunction. Candidates
for primary therapy need well founded information so they can translate
their preferences into their best choice of a treatment modality.
The most reliable QOL
information arises from studies that incorporate essential
methodological and data elements. The number of subjects must be
sufficient to support claims of statistical significance, and the
reports of individual symptoms must come from
patient-centered validated questionnaires. (Reporting from
doctors is notoriously inaccurate.) The best data will include a
patient's assessment of his baseline pre-treatment status in the various
domains of interest followed by interval assessments over a period of
two or more years. Patients' ages, PSA levels, Gleason scores, and
T-stages should be well matched among treatment types. The data
collection period should be as current as possible to insure that
contemporary radiation doses were used; and for RP patients, optimal
information would detail whether nerve-sparing technique was employed.
Single institution reports, although informative, may be biased by
special criteria for patient selection and may reflect special expertise
not evenly shared by the overall clinical community.
One of the best recent
articles that fulfilled these all these criteria is the report in
CANCER by Litwin et al. referenced above. Additional coverage of
this topic in the excellent article by Talcot and D'Amico, JCO Nov.
2003, was reviewed in the first edition of "What Are The Side Effects Of
Your Treatment, Doctor?" (October 2005) in the PCa Commentary, indexed
in the archives under "Quality of Life Issues." Their findings remain
relevant and their presentation of data in tabular form makes the
comparisons easy to grasp.
First, the generalizations based on many review
articles - a tricky prospect when the devil lies so much in the details.
Health-related QOL assessments conventionally divide this subject into
therapy consequences in three main domains of interest.
Urinary symptoms - usually divided into 1),
obstructive and irritative voiding dysfunction - frequently referred to
as "bother; and 2), urinary control (incontinence, often measured by the
number of pads required).
Urinary obstruction and irritation: Brachytherapy
(BT) commonly results in initial irritative dysuria, due to radiation
effect on the urethra. This symptom subsides over a year,
remaining significant in a very few patients ~ possibly 1 - 2%.
Brachytherapy is also associated with initial urinary retention, which
may occur in 34% of men during the first week and decrease to ~10% at 6
months, further decreasing by one year.
Incontinence:
Radical Prostatectomy (RP) is associated with the most incontinence
(less so for younger men ); BT considerably less; andexternal beam
radiotherapy (ERBT ), rarely. But symptoms related to RP decline notably
by the year's end. After RP an indwelling catheter is usually employed
for up to several weeks.
Sexual function
- a difficult area for generalization because of the multiple factors
that influence "success", but often measured as the ability to have an
erection sufficient for vaginal penetration. Assessment in this domain
is clearly related to pre-therapy function and age;
and it is recognized that, independent of any therapy, sexual function
most times diminishes over time.
EBRT is reported to
preserve function slightly better than BT, with a greater likelihood for
potent men to more quickly return to baseline function. Both BT and ERBT
are significantly superior to RP in this area. However, a successful
bilateral nerve sparing RP procedure has been shown in some studies to
overcome this differential (unilateral nerve sparing less so). And, due
to late damage to the cavernosal nerves by radiation induced scarring,
the better initial sexual function associated with radiation can
deteriorate with time, with one study showing a decline in function for
potent men to 53% at five years. (The average age of BT patients in the
past has usually been greater than for RP patients, and this is relevant
for the comparisons.) In some RP cases sexual function somewhat improves
over time. "Sexual bother was more common than urinary or bowel bother
after all three treatments" (Litwin).
Bowel function
is the domain least affected by the three modalities of treatment, as
will be shown in the graphs. However, even optimally applied BT and ERBT
can lead to a minimal incidence of rectal irritation, bleeding, and
incontinence, with EBRT causing less trouble than BT. Bowel dysfunction
is almost never a problem with RP.
However, these
comparison data are best displayed graphically as shown on page 5 of
this Commentary. The graphs are reproduced from the Litwin article (page
2245) with permission from Wiley-Liss, Inc., a subsidiary of John Wiley
& Sons, Inc.
Now, the details - based on the Litwin report of
580 men treated at UCLA between 1999 and 2003, with information obtained
from patient responses to three validated instruments. The follow-up
period was 24 months and ongoing assessments were made at 1, 2, 4, 8,
12, 18 and 24 months. The clinical TMN stage was nearly 100% cT1 or cT2.
Clinical T2 stage was 29.3% for RP; 43.6%, ERBT; and 18.9% for BT.
Treatment mode: RP, 307 men; ERBT, 78; and BT, 90. ERBT dose (3-D
Conformal or IMRT) was 68 - 77 Gy. For BT, monotherapy was used in 74.4%
and was combined with ERBT in 25.6%; and in the BT cohort short term ADT
was used in 23%. For RP patients 80.8% underwent bilateral
nerve-sparing, 10.1% unilateral nerve-sparing, and 9.1% nonnerve-sparing.
Mean age for RP, 60.1 years; ERBT, 70.8; and for BT. 68.4. Median
Gleason score for all modalities was 6; and the PSA ranged between 6 and
8 ng/mL.
The Litwin graphs,
Figures 1 and 2, are reproduced on page 5.
Figure 1: "Sexual
function of men who were potent pre-treatment (having a UCLA
Prostate Cancer Index sexual function score of at least 70, where 100 is
optimal, n = 187 patients).
Figure 2: "Longitudinal
changes in bother scores as measured by the UCLA Prostate Cancer Index.
Bars shown represent the proportion of subjects reporting severe
bother, i.e <25 on a scale where 100 = no bother, at each respective
time point."
Litwin concludes:
"Leveraging descriptive [QOL] data to guide interventions that improve
outcomes adds value to the clinical care we provide during the long
survivorship period that most patients experience."
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