Article

Talcott JA, Rossi C, Shipley WU, Clark JA, Slater JD, Niemierko A, Zietman ALPatient-reported long-term outcomes after conventional and high-dose combined proton and photon radiation for early prostate cancer. JAMA 303: 1046-1053

Center for Outcomes Research, MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 03/2010; 303(11):1046-53. DOI: 10.1001/jama.2010.287
Source: PubMed
ABSTRACT
Increased radiation doses improve prostate cancer control but also increase toxicity to adjacent normal tissue. Proton radiation may attenuate adverse effects.
To determine long-term, patient-reported, dose-related toxicity.
We performed a post hoc cross-sectional survey of surviving participants in the Proton Radiation Oncology Group (PROG) 9509--a randomized trial comparing 70.2 Gy vs 79.2 Gy of combined photon and proton radiation for 393 men with clinically localized prostate cancer (stage T1b-T2b, prostate-specific antigen <15 ng/mL, and no radiographic evidence of metastasis). The estimated 10-year biochemical progression rate for patients receiving standard dose was 32% (95% confidence interval, 26%-39%) compared with 17% (95% confidence interval, 11%-23%) for patients receiving high dose (P < .001). We surveyed 280 of the surviving 337 patients (83%) from April 2007 to September 2008.
Prostate Cancer Symptom Indices, a validated measure of urinary incontinence, urinary obstruction and irritation, bowel problems, and sexual dysfunction, and related quality-of-life instruments.
At a median of 9.4 years after treatment (range, 7.4-12.1 years), participants' demographic and clinical characteristics were similar. Patient-reported outcomes were reported as mean (SD) scale score for standard dose vs high dose: urinary obstruction/irritation (23.3 [13.7] vs 24.6 [14.0]; P = .36), urinary incontinence (10.6 [17.7] vs 9.7 [15.8]; P = .99), bowel problems (7.7 [7.8] vs 7.9 [9.1]; P = .70), sexual dysfunction (68.2 [34.6] vs 65.9 [34.7]; P = .65), and most other outcomes were also similar, although patients receiving standard dose whose cancers had more often progressed expressed less confidence that their cancers were under control (mean [SD] scale score for standard dose, 76.0 [25.4] vs high dose, 86.2 [17.9]; P < .001). Many patients characterized their urinary and bowel function as normal despite reporting symptoms that, for other prostate cancer patients before and early after cancer treatment, caused substantial distress.
Among men with clinically localized prostate cancer, treatment with higher-dose radiation compared with standard dose was not associated with an increase in patient-reported prostate cancer symptoms after a median of 9.4 years.

Full-text

Available from: Andrzej Niemierko
ORIGINAL CONTRIBUTION
Patient-Reported Long-term Outcomes
After Conventional and High-Dose
Combined Proton and Photon Radiation
for Early Prostate Cancer
James A. Talcott, MD, SM
Carl Rossi, MD
William U. Shipley, MD
Jack A. Clark, PhD
Jerry D. Slater, MD
Andrzej Niemierko, PhD
Anthony L. Zietman, MD
P
ROSTATE CANCER IS THE MOST
common nonskin cancer and
the second leading cause of
cancer death in US men. Em-
pirical evidence indicates that increas-
ing the radiation therapy dose im-
proves local control rates.
1
However,
irradiation of nearby nonprostate tis-
sue, which increases in parallel with
treatment doses, produces urinary,
bowel, and sexual dysfunction.
2,3
In-
vestigators have attempted to reduce
toxicity to adjacent normal tissue with
conformal approaches to photon radia-
tion, which use 3-dimensional com-
puted tomographic images to improve
target localization, and radiation blocks
that protect normal tissue.
4,5
One ran-
domized trial has found that confor-
mal radiation therapy reduces physi-
cian-reported toxicity compared with
conventional approaches.
6
Proton
therapy reduces the radiation to non-
targeted adjacent tissue compared with
standard photon (x-ray) radiation by
limiting the dose distal to the target vol-
ume, potentially limiting toxicity from
increased radiation doses.
7,8
Uncon-
Author Affiliations: Center for Outcomes Research,
MGH Cancer Center, Massachusetts General
Hospital, Boston, Massachusetts (Dr Talcott); Loma
Linda University Medical Center, Loma Linda,
California (Drs Rossi and Slater); Department of
Radiation Oncology, Massachusetts General Hospi-
tal, Boston (Drs Shipley, Niemierko, and Zietman);
Center for Health Quality, Outcomes, and Eco-
nomic Research, Edith Nourse Rogers Memorial
Veterans Hospital, Bedford, and Boston University
School of Public Health, Boston, Massachusetts (Dr
Clark); and Harvard Medical School, Boston, Mas-
sachusetts (Drs Talcott, Shipley, Niemierko, and
Zietman).
Corresponding Author: James A. Talcott, MD, SM,
Center for Outcomes Research, Charlestown Navy
Yard, Bldg 120, Sixth Street, Second Floor,
Charlestown, MA 02129 (jtalcott@partners.org).
Context Increased radiation doses improve prostate cancer control but also increase
toxicity to adjacent normal tissue. Proton radiation may attenuate adverse effects.
Objective To determine long-term, patient-reported, dose-related toxicity.
Design, Setting, and Patients We performed a post hoc cross-sectional survey
of surviving participants in the Proton Radiation Oncology Group (PROG) 9509—a
randomized trial comparing 70.2 Gy vs 79.2 Gy of combined photon and proton ra-
diation for 393 men with clinically localized prostate cancer (stage T1b-T2b, prostate-
specific antigen 15 ng/mL, and no radiographic evidence of metastasis). The esti-
mated 10-year biochemical progression rate for patients receiving standard dose was
32% (95% confidence interval, 26%-39%) compared with 17% (95% confidence
interval, 11%-23%) for patients receiving high dose (P .001). We surveyed 280 of
the surviving 337 patients (83%) from April 2007 to September 2008.
Main Outcome Measures Prostate Cancer Symptom Indices, a validated mea-
sure of urinary incontinence, urinary obstruction and irritation, bowel problems, and
sexual dysfunction, and related quality-of-life instruments.
Results At a median of 9.4 years after treatment (range, 7.4-12.1 years), partici-
pants’ demographic and clinical characteristics were similar. Patient-reported out-
comes were reported as mean (SD) scale score for standard dose vs high dose: urinary
obstruction/irritation (23.3 [13.7] vs 24.6 [14.0]; P=.36), urinary incontinence (10.6
[17.7] vs 9.7 [15.8]; P =.99), bowel problems (7.7 [7.8] vs 7.9 [9.1]; P=.70), sexual
dysfunction (68.2 [34.6] vs 65.9 [34.7]; P=.65), and most other outcomes were also
similar, although patients receiving standard dose whose cancers had more often pro-
gressed expressed less confidence that their cancers were under control (mean [SD]
scale score for standard dose, 76.0 [25.4] vs high dose, 86.2 [17.9]; P .001). Many
patients characterized their urinary and bowel function as normal despite reporting
symptoms that, for other prostate cancer patients before and early after cancer treat-
ment, caused substantial distress.
Conclusion Among men with clinically localized prostate cancer, treatment with higher-
dose radiation compared with standard dose was not associated with an increase in
patient-reported prostate cancer symptoms after a median of 9.4 years.
JAMA. 2010;303(11):1046-1053 www.jama.com
1046 JAMA, March 17, 2010—Vol 303, No. 11 (Reprinted with Corrections) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 1
trolled studies have found that proton
radiation allows increased radiation
doses with modestly increased physi-
cian-reported toxicity.
9,10
The Proton Radiation Oncology
Group (PROG) 9509 is a randomized
trial performed at Massachusetts Gen-
eral Hospital, Boston, and the Loma
Linda University Medical Center, Loma
Linda, California, that assigned 393 pa-
tients with early prostate cancer to a
total dose of either 70.2 Gy (standard-
dose) or 79.2 Gy (high-dose) compris-
ing both photon and proton radiation.
Improved biochemical recurrence was
evident at a median 5.5-year follow-
up,
11
and the benefit persisted at a me-
dian 8.9-year follow-up (10-year esti-
mated biochemical recurrence, 17%
[95% confidence interval {CI}, 11%-
23%] vs 32% [95% CI, 26%-39%];
P .001).
12
Physician-reported acute
and late genitourinary and gastrointes-
tinal toxicity, measured using the Ra-
diation Therapy Oncology Group cri-
teria,
13
was low for both groups.
14
However, patient-reported out-
comes are the most sensitive and valid
measures of treatment-related morbid-
ity. To better evaluate the toxicity from
these treatments, we performed a post
hoc survey to determine long-term (8
years), patient-reported quality-of-life
outcomes. We report the results of that
survey.
METHODS
Patient Population
PROG 9509 is a randomized con-
trolled trial to compare 2 different ra-
diation doses delivered by conformal
techniques. All patients received con-
formal photon (x-ray) therapy to a fixed
dose of 50.4 Gy, with the planned boost
dose, delivered using proton therapy,
to either 19.8 Gy or 28.8 Gy, using a
radiobiological effectiveness proton-
to-photon ratio of 1.1, for total doses
of 70.2 Gy (conventional dose) or 79.2
Gy (high dose), respectively. No pa-
tients received neoadjuvant, concur-
rent, or adjuvant androgen-depriva-
tion therapy.
Patients were enrolled at 2 centers
(previously mentioned). Eligible pa-
tients had clinically localized adeno-
carcinoma of the prostate (defined as
stage T1b through T2b tumors [using
1992 American Joint Committee on
Cancer criteria]), serum prostate-
specific antigen (PSA) levels less than
15 ng/mL, and no radiographic evi-
dence of metastatic disease. Between
January 1996 and December 1999, 393
patients were randomized centrally
without blocks and stratified by pre-
treatment serum PSA levels (4 ng/mL
vs 4-15 ng/mL) and nodal status (NX
vs N0). The clinical target volume for
the proton boost was the prostate with
a 5-mm margin with an additional 7 to
10 mm added for a planning target vol-
ume, according to the technical require-
ments of the treating devices at the 2
participating institutions.
Data Collection
and Outcome Measures
PROG 9509 was designed to have 80%
power to detect a 20% improvement in
freedom from biochemical failure at 5
years, with additional follow-up con-
tingent on additional funding. The ini-
tial protocol specified physician-
reported monitoring of toxicity, which
is less sensitive than patient-reported
measures. To address this deficiency,
the current study attempted to con-
tact all living patients who had been en-
rolled in PROG 9509. After receiving
institutional review board approval, pa-
tients were mailed a cover letter ex-
plaining the study, its voluntary na-
ture, the requirements for participation,
the study questionnaire, and a post-
paid opt-out card to indicate the choice
not to participate. The returned sur-
vey was accepted documentation of in-
formed consent. Data were collected
through the staff of the Center for Out-
comes Research at Massachusetts Gen-
eral Hospital. Data management was
performed at quality assurance office of
clinical trials, the data management cen-
ter for all studies of the Dana Farber/
Partners Cancer Care.
Patients were asked to complete self-
administered questionnaires, which in-
cluded previously validated assess-
ments of sexual function, urinary and
bowel complications of treatment, and
disease-focused quality of life.
15,16
Urinary, Sexual,
and Bowel Function
Study questionnaires included the 4
prostate cancer symptom indices (PCSI)
to assess urinary incontinence, uri-
nary obstruction and irritation, bowel
dysfunction, and sexual dysfunction.
The urinary incontinence index con-
tains 3 questions gauging the degree of
urinary control. The urinary obstruc-
tion and irritation index contains 5
questions assessing hesitancy, fre-
quency, nocturia, dysuria, and ur-
gency. The bowel problems index in-
cludes questions regarding diarrhea,
urgency of bowel movements, rectal
pain, bleeding, passing mucus, abdomi-
nal cramping, and tenesmus. Sexual
dysfunction questions assess patients’
reports of their erections (firmness and
difficulty acquiring and maintaining
them), orgasm, and ejaculation. In ad-
dition, we administered the 5-item
sexual function and quality-of-life scale
developed in the Medical Outcomes
Study.
17
In addition, we measured patient as-
sessments of other aspects of their medi-
cal condition and treatment choices.
The informed decision scale (=.79) as-
sesses perceptions of having sufficient
information when choosing a treat-
ment, being fully informed by one’s
physicians, and experiencing satisfac-
tion with one’s choices.
16
The deci-
sion regret scale is a 5-item scale that
asks patients to reflect on their spe-
cific treatment decision. Patients are
asked if they made the right decision,
whether they would make the same
choice if necessary, and whether they
thought their decision caused them
harm. The cancer control scale as-
sesses confidence that one’s cancer is
under control, worries about recur-
rence, and misgivings about the effi-
cacy of treatment based on patient un-
derstanding of clinical events.
16
Each PCSI function or bother index
was scored by summing responses to
the component items and then stan-
dardizing that value to vary from 0 (no
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
©2010 American Medical Association. All rights reserved. (Reprinted with Corrections) JAMA, March 17, 2010—Vol 303, No. 11 1047
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 2
reported symptoms) to 100 (maxi-
mum possible dysfunction reported on
each scale item). All other scales also
ranged from 0 to 100 scores, but with
the exception of the regret scale, for
which higher scores indicated greater
regret, higher scores indicated better
quality of life (eg, for informed deci-
sion, higher scores indicate greater con-
fidence that one’s decision making was
well informed). For the function scales,
scores were calculated only if partici-
pants responded to all scale items, while
the remainder required responses to at
least half the scale items. To assist in-
terpretation of numerical scale scores,
we parsed the PCSI results as normal,
intermediate, or poor function for each
PCSI scale, using our previously de-
scribed method
18
based on patient-
reported distress or bother for each
functional scale item. The method char-
acterizes a patient’s function as nor-
mal only if the patient’s response to each
scale item was associated with little or
no distress in other prostate cancer pa-
tients, poor if any response was asso-
ciated with great distress, and interme-
diate for all other patients.
The questionnaire also assessed age,
race, marital status, and education, with
all response options defined by the in-
vestigators. We included race because
of published data suggesting that pa-
tient-reported outcomes may be influ-
enced by race.
19,20
Statistical Methods
Analyses were performed using Stata ver-
sion 8.1 (Stata Institute, College Sta-
tion, Texas). All reported P values are
2-sided. To adjust for multiple testing,
we defined a significant P value as .01.
For categorical variables, we used Fisher
exact test, and for continuous vari-
ables, the Wilcoxon rank-sum test
(Mann-Whitney). Using the mean (SD)
bowel score of 8, an of .05, 2-sided
tests, and the observed number of cases
provided information to calculate bowel
problems scores (134 and 137), the
power is as follows: 0.54 for detecting
the difference in mean scores of 2 (SD,
0.25), 0.87 for detecting the difference
in mean scores of 3 (SD, 0.375), and 0.98
for detecting the difference in mean
scores of 4 (SD, 0.5). Using the conser-
vative Chebycheff Inequality analy-
sis,
21
our study had adequate power
(81%) to detect group differences of
0.375 SDs; a marginally clinically sig-
nificant difference in bowel problems,
the symptom most specific to external
beam radiation; and excess power (92%)
to detect a difference of 0.5 SD.
RESULTS
Between August 2007 and December
2008, we attempted to survey the 393
patients enrolled in PROG 9509. Of
these, 1 patient had withdrawn con-
sent before treatment and we con-
firmed 55 deaths, leaving 337 patients
eligible for study. Of these, 14 pa-
tients could not be contacted despite
multiple efforts, and 43 were con-
tacted but did not participate in the
study (27 patients refused because they
were uninterested [15 patients], too ill
[8 patients], or declined for other rea-
sons [4 patients], and the remaining 16
Table 1. Patient-Reported Sociodemographic and Clinical Characteristics
a
Characteristic
No. (%)
b
P
Value
c
Standard
Dose High Dose All Patients
No. of patients 139 141 280
Age at time of treatment,
median (range), y
66.5
(45.2-79.5)
66.8
(47.6-77.0)
66.6
(45.2-79.5)
.63
Age at time of survey,
median (range), y
76.0
(55.1-87.4)
76.1
(56.8-87.8)
76.0
(55.1-87.8)
.55
Time since treatment at time
of survey, median (range), y
9.3
(7.4-12.1)
9.5
(7.4-12.1)
9.4
(7.4-12.1)
.30
Race/ethnicity
White 125 (91) 132 (95) 257 (93)
African American 9 (7) 2 (1) 11 (4)
Asian 2 (1) 1 (1) 3 (1) .19
Hispanic 2 (1) 4 (3) 6 (2)
Gave no response 1 2 3
Marital status
Never married 2 (1) 2 (1) 4 (1)
Currently married 117 (84) 121 (86) 237 (85)
.85
Separated, divorced, or widowed 20 (14) 17 (12) 37 (13)
Gave no response 0 1 1
Educational attainment
High school 25 (18) 27 (19) 52 (19)
Attended college 66 (47) 78 (56) 144 (52)
.19
Attended graduate school 48 (35) 34 (24) 82 (30)
Gave no response 0 2 2
PSA ever increased after treatment
Yes 51 (38) 19 (14) 70 (25)
No 69 (51) 107 (77) 176 (64)
.001
Don’t know 16 (12) 13 (9) 29 (11)
Gave no response 3 2 5
Received another local prostate
cancer treatment
Radical prostatectomy 3 (2) 0 3 (1)
Cryotherapy 11 (8) 1 (1) 12 (4) .001
No local therapy 125 (90) 140 (99) 265 (95)
Received hormonal therapy
for prostate cancer
after radiation treatment
18 (13) 9 (6) 27 (10) .05
Abbreviation: PSA, prostate-specific antigen.
a
Self-reported responses are for 289 patients with early prostate cancer who underwent treatment under the Proton
Radiation Oncology Group (PROG) 9509 and completed the quality-of-life survey.
b
Values are shown as No. (%) unless otherwise indicated.
c
Standard-dose vs high-dose patients, Wilcoxon rank-sum (Mann-Whitney) test or Fisher exact test.
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
1048 JAMA, March 17, 2010—Vol 303, No. 11 (Reprinted with Corrections) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 3
patients expressed interest but did not
return questionnaires). Although liv-
ing nonparticipants were similar to par-
ticipants in age, deceased patients were
older (mean difference, 7.0 years;
P .001). The 280 respondents repre-
sented 83% of eligible enrolled pa-
tients not known to have died. Of these,
139 patients had been randomized to
the standard-dose treatment group and
141 patients to the high-dose group.
Pretreatment Characteristics
The median follow-up for the entire
group was 9.4 years (range, 7.4-12.1
years) (T
ABLE 1). Median participant
age at survey completion was 76.0 years
(range, 55.1-87.8 years). Patients were
demographically similar and highly
educated with 257 patients (93%) being
of white race, 237 (85%) currently mar-
ried, 144 (52%) attended college, and
another 82 (30%) attended graduate
school. Reflecting the benefit of high-
dose treatment, patients in the standard-
dose group more often reported post-
treatment elevation of PSA (51 patients
[37%] vs 8 patients [14%]; P .001)
and subsequent local therapy with
either radical prostatectomy or cryo-
therapy (14 patients [10%] vs 3 pa-
tients [1%]; P =.002). Cancer progres-
sion, indicated by either PSA increase
or salvage therapy, was more frequent
in standard-dose patients (63 patients
[45%]; vs 30 patients [21%]; P .001).
Functional Outcomes
Using the PCSI scales, there was little
evidence of added urinary, bowel, or
sexual dysfunction in the high-dose
treatment group (T
ABLE 2). Patient-
reported urinary obstruction and irri-
tation (mean scale score: standard dose,
23.3 vs high dose, 24.6; P =.36), uri-
nary incontinence (10.6 vs 9.7; P =.99),
bowel problems (7.7 vs 7.9; P =.70),
sexual dysfunction (68.2 vs 65.9;
P =.65) were similar, as were other qual-
ity-of-life measures. Other measures of
aspects of sexual and marital function-
ing were also similar. As for the nu-
merical functional scale results, we
found no differences between treat-
ment groups when results were re-
ported by level of function (normal, in-
termediate, or poor) (T
ABLE 3).
Perceived Health and Attitudes
Toward Treatment Decisions
Using measures we developed to evalu-
ate patient appraisals of their prostate
cancer course over time, we found no
evidence that treatment groups dif-
fered in either their worry about health
or their attentiveness to the PSA test
(T
ABLE 4). Patients in the standard-
dose group, who had more often pro-
gressed, were less confident that their
prostate cancer was under control
(mean score, 76.0 vs 86.2; P .001).
Treatment groups had similar confi-
Table 2. Patient Responses for Urinary, Bowel, and Sexual Function and Bother or Distress
a
Scale
Prostate Cancer Symptom Indices Response Score
P
Value
b
Standard Dose High Dose All
No. of
Patients Mean (SD)
No. of
Patients Mean (SD)
No. of
Patients Mean (SD)
Urinary obstruction and irritation
Urinary obstruction
and irritation
c
132 23.3 (13.7) 132 24.6 (14.0) 264 24.0 (13.9) .36
Urinary obstruction
and irritation, bother
d
123 12.0 (16.5) 123 11.9 (15.1) 246 12.0 (15.8) .80
Urinary incontinence
Urinary incontinence
c
131 10.6 (17.7) 134 9.7 (15.8) 265 10.2 (16.7) .99
Urinary incontinence, bother
d
133 10.3 (19.2) 134 8.4 (15.3) 267 9.4 (17.4) .63
Urinary incontinence quality
of life
e
129 92.2 (16.4) 134 93.3 (13.6) 263 92.7 (15.0) .72
Bowel problems
Bowel problems
c
134 7.7 (7.8) 137 7.9 (9.1) 271 7.8 (8.4) .70
Bowel problems, bother
d
131 5.5 (10.2) 131 7.9 (12.4) 262 6.7 (11.4) .10
Sexual function
Sexual dysfunction
c
132 68.2 (34.6) 127 65.9 (34.7) 259 67.1 (34.6) .65
Sexual problems, bother
d
124 44.5 (24.1) 122 45.1 (22.2) 246 44.8 (23.1) .95
Sexual intimacy
f
128 67.7 (28.8) 123 70.7 (27.4) 251 69.2 (28.1) .44
Sexual confidence
f
129 38.0 (30.7) 123 42.2 (31.3) 252 40.1 (31.0) .30
Masculine self-esteem
f
130 78.4 (23.5) 123 80.1 (20.8) 253 79.2 (22.2) .92
Marital affect
f
93 91.7 (17.7) 99 91.8 (17.0) 192 91.8 (17.3) .83
a
Self-reported responses are for 287 patients with early prostate cancer who underwent treatment under the Proton Radiation Oncology Group (PROG) 9509 and completed the
study survey.
b
Standard-dose vs high-dose patients, Wilcoxon rank-sum test.
c
Scales assesses the frequency or severity of symptoms. Scales range from 0 (no symptoms) to 100 (maximum symptoms).
d
Symptom bother scales assess the bother or distress patients feel from the symptoms assessed in each scale. Scales range from 0 (no bother or distress) to 100 (maximum
bother or distress).
e
Measures the impact of the symptom by inquiring about its direct consequences, such as feeling unclean or worry about public embarrassment. Scale ranges from 0 (lowest
quality of life) to 100 (highest quality of life).
f
Scale ranges from 0 (lowest quality of life) to 100 (highest quality of life).
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
©2010 American Medical Association. All rights reserved. (Reprinted with Corrections) JAMA, March 17, 2010—Vol 303, No. 11 1049
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 4
dence that they had made a well-
informed treatment decision, al-
though patients in the standard-dose
group tended to express more regret
(mean score, 12.7 vs 9.2; P =.02).
Cancer Progression and Outcomes
To assess the affect of cancer progres-
sion on our results, we performed
analysis of variance multiple regres-
sion models that controlled for pro-
gression. While progression was inde-
pendently associated with urinary
obstruction and irritation, greater treat-
ment regret, reduced confidence of can-
cer control, and greater health worry,
there was no significant association be-
tween the treatment group and any out-
come variable and study group (data not
shown).
Level of Function vs Perceived
Level of Function
To compare the patient’s level of func-
tion based on prior correlations with pa-
tient-reported bother to the patients’
self-description, we asked patients to se-
lect the term that best described their
function with regard to urinary incon-
tinence, urinary obstruction and irri-
tation, and bowel problems (T
ABLE 5).
From 92% to 99% of patients with nor-
mal function agreed with that assess-
ment. However, patients were much
more often in disagreement when their
function was rated as abnormal. For uri-
nary obstruction and irritation, and
bowel problems, more than two-
thirds of patients with intermediate
function described their function as
normal and more than half classified as
poor characterized their function as in-
termediate. For urinary incontinence,
patients were more likely to agree that
their function was abnormal; only 45%
of patients whose function was classi-
fied as intermediate described it as nor-
mal. Few patients were classified as
having poor function for urinary in-
continence.
COMMENT
This study, reporting patient-reported
quality-of-life outcomes after the long-
est published follow-up after radia-
tion therapy for prostate cancer, indi-
cates that radiation at the higher doses
now commonly used were not associ-
ated with increased patient-reported,
long-term, treatment-related urinary,
bowel, or sexual dysfunction or re-
lated quality-of-life outcomes. In par-
ticular, a 9-Gy increased boost of pro-
ton radiation sufficient to reduce
estimated 10-year biochemically PSA-
detected treatment failure from 32% to
17% was associated with no addi-
tional treatment-related dysfunction.
Patients who received the less effica-
cious standard-dose radiation re-
ported less confidence that their can-
cers were under control and greater
regret about their treatment decisions—
differences that reflected their more fre-
quent disease progression, but no dif-
ference in other measures of their
quality of life, including attitudes to-
ward their cancers and their health.
Several possible explanations for
these unexpected results arise, which
are not mutually exclusive. First, an ef-
ficacious increased radiation dose does
not increase long-term toxicity to ad-
jacent normal tissues if given using
techniques that minimize dose to
Table 3. Long-term Level of Function Based on Patient Distress or Bother
Treatment-Related
Function and Group
Level of Function,
No. of Patients (%) [95% CI]
a
P
ValueNormal Intermediate Poor
Urinary obstruction
and irritation
Standard dose 37 (27) [19-35] 64 (46) [38-55] 38 (27) [20-36]
High dose 26 (18) [12-26] 73 (52) [43-60] 42 (30) [22-38] .27
All patients 63 (23) [18-28] 137 (49) [43-55] 80 (29) [23-34]
Urinary incontinence
Standard dose 84 (64) [55-72] 42 (32) [24-41] 5 (4) [1-9]
High dose 84 (63) [54-71] 45 (34) [26-42] 5 (4) [1-8] .97
All patients 168 (63) [57-69] 87 (33) [27-39] 10 (4) [2-7]
Bowel problems
Standard dose 39 (29) [22-38] 68 (51) [42-59] 27 (20) [14-28]
High dose 42 (31) [22-39] 69 (50) [42-59] 26 (19) [13-27] .96
All patients 81 (30) [24-36] 137 (51) [44-57] 53 (20) [15-25]
Sexual function
Standard dose 9 (7) [3-12] 24 (18) [12-26] 99 (75) [67-82]
High dose 9 (7) [3-13] 25 (20) [13-28] 93 (73) [65-81] .95
All patients 18 (7) [4-11] 49 (19) [14-24] 192 (74) [68-79]
Abbreviation: CI, confidence interval.
a
For each symptom, normal function indicates that the patient reported no bothersome symptoms on any item in the
scale, intermediate function indicates at least 1 moderately bothersome symptom but no highly bothersome symp-
tom, and poor function indicates at least 1 highly bothersome symptom.
Table 4. Measured Patient Attitudes to Their Prostate Cancer, Perceived Health Status, and
Past Treatment Decisions
a
Scale
b
Patient Attitudes by Group, Mean (SD)
c
P
ValueStandard Dose High Dose All
Health worry 19.1 (20.8) 16.5 (16.6) 17.8 (18.8) .73
PSA concern 69.0 (32.8) 69.7 (34.6) 69.3 (33.6) .99
Cancer control 76.0 (25.4) 86.2 (17.9) 81.1 (22.5) .001
Informed decision 78.4 (22.5) 81.5 (21.3) 79.9 (21.9) .14
Regret 12.7 (21.5) 9.2 (19.1) 10.9 (20.4) .02
Abbreviation: PSA, prostate-specific antigen.
a
Self-reported responses are for 287 patients with early prostate cancer who underwent treatment in the Proton Ra-
diation Oncology Group (PROG) 9509 and completed the study survey.
b
Health worry measures the patient’s beliefs about his overall health; PSA concern measures the intensity of patient
attention to PSA level; cancer control measures the patient’s beliefs about how well cancer is under control; in-
formed decision measures the patient’s confidence that treatment decision was well-informed; and regret measures
regret about treatment choice.
c
Scores are based ona0to100scale with better quality of life indicated by higher scores, with the exception of regret.
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
1050 JAMA, March 17, 2010—Vol 303, No. 11 (Reprinted with Corrections) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 5
nearby critical tissues, such as proton
beam. In this sense, our results may be
taken as validating this technology and
confirm the similar physician-
reported short- and long-term toxicity
for standard-dose and high-dose pa-
tients initially reported.
11
Alternatively, high-dose patients may
have experienced increased toxicity ear-
lier in their course that resolved dur-
ing the nearly 10 years of follow-up. It
is well recognized that rectal bleeding
may resolve years after radiation, al-
though hematuria has been reported to
progressively increase.
22
Sexual dys-
function increases progressively in this
age group whether they have had ra-
diation treatment or not, and it may not
be possible to detect a further incre-
ment due to the extra radiation dose
against the increasing background dys-
function.
A third explanation is that standard-
dose patients experienced less treat-
ment-related toxicity, but the direct
consequences of more frequent sal-
vage therapy or the discouraging im-
plications of cancer progression elimi-
nated their advantage. The urinary
obstruction and irritation symptom in-
creased early after external beam ra-
diation but not after the first year,
3
was
strongly associated with cancer pro-
gression, but after adjusting for pro-
gression, not with the treatment group.
Other treatment-related symptoms, in-
cluding bowel problems, the adverse
effect most specific to external beam ra-
diation therapy; urinary inconti-
nence, the adverse effect most specific
to salvage surgery and cryotherapy; and
sexual dysfunction, associated with sur-
gery, cryotherapy, and androgen-
deprivation therapy, were not signifi-
cantly associated with progression.
Fourth, patients who underwent
high-dose treatment did experience
greater treatment-related toxicity but
have adapted to their condition over
time and no longer notice or report it.
Our data documenting that patients fre-
quently rate their function as normal,
despite documented organ-specific
symptoms, indirectly suggests such an
adaptation to a new normal.
Fifth, highly motivated men may be
more satisfied with the outcome of a
technologically novel therapy that, in
many cases, they actively researched
and sought. Proton beam is undoubt-
edly one such therapy.
Finally, our follow-up of study par-
ticipants is incomplete. Of the origi-
nal 393 participants in PROG 9509, 55
(14%) died and an additional 58 pa-
tients (14.8%) did not participate in the
survey, reducing study power and rais-
ing the possibility of bias. However,
no differences in overall survival
between treatment groups have yet
emerged (78% vs 83%; P =.41),
12
treat-
ment-related morbidity has little effect
on survival, and our sample was bal-
anced between study groups and ad-
equate to detect clinically meaningful
differences.
To conclude that additional dose is
not associated with additional toxic-
ity, particularly when using highly sen-
sitive patient-reported measures, runs
contrary to the widely accepted asso-
ciation between radiation dose and tox-
icity. However, data comparing out-
comes after different radiation doses are
surprisingly sparse.
23
In one random-
ized trial, prostate cancer patients who
received 78 Gy reported more fre-
quent bowel movements compared
with those who received 70 Gy, but no
other differences in bowel or sexual
symptoms.
24
In another, which com-
pared 64 to 74 Gy after 3 to 6 months
of neoadjuvant hormonal treatment, the
Table 5. Level of Urinary, Bowel, and Sexual Function vs Patient-Rated Function
a
Functional Scale
and Measured Level
of Function
b
Current Functional Level
No. of Patients (%) [95% CI]
P
ValueNormal Intermediate Poor
Urinary obstruction
and irritation
Normal 58 (92) [82-97] 5 (8) [3-18] 0 [0-6]
Intermediate 89 (69) [60-77] 37 (29) [21-37] 3 (2) [0-7] .001
Poor 15 (19) [11-30] 52 (67) [55-77] 11 (14) [7-24]
Urinary incontinence
Normal 149 (92) [87-96] 13 (8) [4-13] 0 [0-2]
Intermediate 38 (45) [33-56] 46 (54) [43-65] 1 (1) [0-6] .001
Poor 1 (10) [0-44] 3 (30) [7-65] 6 (60) [26-88]
Bowel problem
Normal 79 (99) [93-100] 1 (1) [0-7] 0 [0-4]
Intermediate 110 (81) [74-88] 25 (18) [12-26] 0 [0-3] .001
Poor 20 (38) [25-52] 27 (51) [37-65] 6 (11) [4-23]
Abbreviation: CI, confidence interval.
a
Patients with early prostate cancer who underwent treatment in the Proton Radiation Oncology Group (PROG) 9509
and completed the study survey.
b
The measured level of function was determined by same indicators as for Table 3.
Patients indicated their self-reported level of function in items asking them to consider their overall function for each
symptom.
Table 6. Comparison of Mean Urinary,
Bowel, and Sexual Function Scores
a
PROG 9509
Dysfunction
Boston Area,
All Patients
Cohort
Study
No. of patients 280 97
Time of
follow-up,
median, y
9.4 5.9
Age at survey,
median, y
76.0 75.0
Urinary
obstruction
and irritation,
mean score
(SD)
24.0 (13.9) 21.8 (14.5)
Urinary
incontinence,
mean score
(SD)
10.2 (16.7) 11.2 (18.0)
Bowel problem,
mean score
(SD)
7.8 (8.4) 10.6 (13.2)
Sexual
dysfunction,
mean score
(SD)
67.1 (34.6) 76.3 (30.8)
Abbreviation: SD, standard deviation.
a
Patients with early prostate cancer who underwent treat-
ment in the Proton Radiation Oncology Group (PROG)
9509 were compared with long-term follow-up of pa-
tients undergoing external beam radiation therapy (pho-
ton) in a contemporaneous prospective cohort study. Table
is modified from Clark and Talcott.
28
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
©2010 American Medical Association. All rights reserved. (Reprinted with Corrections) JAMA, March 17, 2010—Vol 303, No. 11 1051
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 6
calculated radiation dose to the penile
bulb was associated with erectile dys-
function at 2 years after treatment but
not to the assigned treatment dose.
25
A
trial of a hypofractionated schedule
compared with a standard schedule
found similar 5-year urinary and bowel
symptoms, but efficacy was also iden-
tical.
26
A further problem in assessing out-
comes after proton beam or more
widely available radiation modalities is
that, despite their frequent use, little
long-term patient-reported data are
available. Most reports have at most
2-year follow-up,
3
but occasionally ex-
tend to 3 years.
27
However, at a me-
dian of 5.5 years (range, 4-8 years),
patients in a contemporaneous multi-
center prospective cohort study
28
who
had undergone external beam photon
radiation reported roughly compa-
rable outcomes (T
ABLE 6).
Some data support the explanation
that symptoms become less noticeable
over time. Korfage et al
29
found that pa-
tients trivialized dysfunction, espe-
cially sexual dysfunction, associating it
with old age, and assigned adverse ef-
fects to treatment—not disease. In their
studies, disease-specific instruments de-
tected dysfunction, but they also de-
tected response shift as patients adapted
to changed health. Yu et al
30
found a
strong correlation between optimism
and eating ability in Chinese patients
treated for nasopharyngeal carci-
noma, indicating that psychological sta-
tus influenced reported function.
These data challenge the assumption
that the quality-of-life impact of persist-
ing dysfunction is stable and can be ex-
trapolated from naive expectations or
early treatment experience. Any metric
that assumes a stable relationship be-
tween symptoms and quality of life over
time, such as quality-adjusted life-year,
requires empirical validation of the as-
sumption of stability over time, whether
or not the analysis discounts benefits over
time.
31
To the extent that patients adapt
to treatment-related dysfunction, the as-
sumption that the impact of treatment-
related dysfunction is stable underesti-
mates the net benefit of treatment.
Prostate cancer is now being de-
tected and treated at earlier ages and
cured patients may live for decades with
treatment adverse effects. Long-term
outcomes have thus become a central
factor in patient treatment decisions,
but to date, long-term patient-
reported data are lacking for both sur-
gery and radiation. The experimental
higher dose in PROG 9509 is now com-
mon in clinical practice. Among men
with clinically localized prostate can-
cer, treatment with higher-dose radia-
tion compared with standard dose was
not associated with an increase in pa-
tient-reported prostate cancer symp-
toms after a median of 9.4 years.
Author Contributions: Dr Talcott had full access to all
of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Talcott, Shipley, Slater,
Zietman.
Acquisition of data: Talcott, Rossi, Zietman.
Analysis and interpretation of data: Talcott, Clark,
Niemierko, Zietman.
Drafting of the manuscript: Talcott, Clark, Slater,
Zietman.
Critical revision of the manuscript for important in-
tellectual content: Talcott, Rossi, Shipley, Clark, Slater,
Niemierko, Zietman.
Statistical analysis: Talcott, Clark, Niemierko.
Obtained funding: Talcott, Shipley, Zietman.
Administrative, technical, or material support: Rossi,
Slater,
Study supervision: Talcott, Slater, Zietman.
Financial Disclosures: Dr Slater reported that his
brother is an employee of Optivus Technology, a com-
pany that builds proton radiation facilities. The other
authors reported no disclosures.
Funding/Support: This research was supported by the
Bertucci Genitourinary Cancer Research Fund, Mas-
sachusetts General Hospital, Boston, MA.
Role of the Sponsor: The Bertucci Genitourinary Can-
cer Research Fund had no role in the design and con-
duct of the study; collection, management, analysis,
and interpretation of the data; and preparation, re-
view, or approval of the manuscript.
Additional Contributions: We would like to acknowl-
edge Anita E. Rodrigues, BA, Center for Outcomes Re-
search, Massachusetts General Hospital, Boston; and
Catherine Reyes, BS, Center for Outcomes Research,
Massachusetts General Hospital, Boston, MA, and cur-
rently MD candidate, Harvard Medical School, for con-
tacting eligible patients, enrolling patients, and car-
rying out data collection; and Mary M. Lunt, BSN, Loma
Linda University Medical Center, Loma Linda, CA, for
contacting potential study participants. Ms Rod-
rigues and Ms Reyes were compensated for their roles
in the study. Ms Lunt, an employeee at LLUMC, was
not.
REFERENCES
1. Jacob R, Hanlon AL, Horwitz EM, Movsas B, Uzzo
RG, Pollack A. The relationship of increasing radio-
therapy dose to reduced distant metastases and mor-
tality in men with prostate cancer. Cancer. 2004;
100(3):538-543.
2. Litwin MS, Hays RD, Fink A, et al. Quality-of-life
outcomes in men treated for localized prostate cancer.
JAMA. 1995;273(2):129-135.
3. Talcott JA, Manola J, Clark JA, et al. Time course
and predictors of symptoms after primary prostate
cancer therapy. J Clin Oncol. 2003;21(21):3979-
3986.
4. Hanks GE, Hanlon AL, Schultheiss TE, et al. Dose
escalation with 3D conformal treatment: five year out-
comes, treatment optimization, and future directions.
Int J Radiat Oncol Biol Phys. 1998;41(3):501-
510.
5. Wachter S, Gerstner N, Goldner G, Potzi R,
Wambersie A, Potter R. Rectal sequelae after confor-
mal radiotherapy of prostate cancer: dose-volume his-
tograms as predictive factors. Radiother Oncol. 2001;
59(1):65-70.
6. Dearnaley DP, Khoo VS, Norman AR, et al. Com-
parison of radiation side-effects of conformal and con-
ventional radiotherapy in prostate cancer: a ran-
domised trial. Lancet. 1999;353(9149):267-272.
7. Loeffler JS, Smith AR, Suit HD. The potential role
of proton beams in radiation oncology. Semin Oncol.
1997;24(6):686-695.
8. Schulz-Ertner D, Tsujii H. Particle radiation therapy
using proton and heavier ion beams. J Clin Oncol.
2007;25(8):953-964.
9. Benk VA, Adams JA, Shipley WU, et al. Late rectal
bleeding following combined X-ray and proton high
dose irradiation for patients with stages T3-T4 pros-
tate carcinoma. Int J Radiat Oncol Biol Phys. 1993;
26(3):551-557.
10. Yonemoto LT, Slater JD, Rossi CJ Jr, et al. Com-
bined proton and photon conformal radiation therapy
for locally advanced carcinoma of the prostate: pre-
liminary results of a phase I/II study. Int J Radiat On-
col Biol Phys. 1997;37(1):21-29.
11. Zietman AL, DeSilvio ML, Slater JD, et al. Com-
parison of conventional-dose vs high-dose confor-
mal radiation therapy in clinically localized adenocar-
cinoma of the prostate: a randomized controlled trial.
JAMA. 2005;294(10):1233-1239.
12. Zietman AL, Bae K, Slater JD, et al. Randomized
trial comparing conventional-dose with high-dose
conformal radiation therapy in early-stage adenocar-
cinoma of the prostate: long-term results from Pro-
ton Radiation Oncology Group/American College
of Radiology 95-09. J Clin Oncol. 2010;28:1106-
1111.
13. Lawton CA, Won M, Pilepich MV, et al. Long-
term treatment sequelae following external beam ir-
radiation for adenocarcinoma of the prostate: analy-
sis of RTOG studies 7506 and 7706. Int J Radiat Oncol
Biol Phys. 1991;21(4):935-939.
14. Shipley WU, Verhey LJ, Munzenrider JE, et al. Ad-
vanced prostate cancer: the results of a randomized
comparative trial of high dose irradiation boosting with
conformal protons compared with conventional dose
irradiation using photons alone. Int J Radiat Oncol Biol
Phys. 1995;32(1):3-12.
15. Clark JA, Talcott JA. Symptom indexes to assess
outcomes of treatment for early prostate cancer. Med
Care. 2001;39(10):1118-1130.
16. Clark JA, Bokhour BG, Inui TS, Silliman RA, Talcott
JA. Measuring patients’ perceptions of the outcomes
of treatment for early prostate cancer. Med Care. 2003;
41(8):923-936.
17. Stewart A, Ware J Jr. Measuring Function Status
and Well-Being: The Medical Outcomes Study
Approach. Durham, NC: Duke University Press; 1992.
18. Talcott JA, Clark JA, Manola J, Mitchell SP. Bring-
ing prostate cancer quality of life research back to the
bedside: translating numbers into a format that pa-
tients can understand. J Urol. 2006;176(4 pt 1):
1558-1563.
19. Do YK, Carpenter WR, Spain P, et al. Race, health-
care access and physician trust among prostate can-
cer patients. Cancer Causes Control. 2010;21(1):
31-40.
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
1052 JAMA, March 17, 2010—Vol 303, No. 11 (Reprinted with Corrections) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 7
20. Jayadevappa R, Johnson JC, Chhatre S, Wein AJ,
Malkowicz SB. Ethnic variation in return to baseline
values of patient-reported outcomes in older pros-
tate cancer patients. Cancer. 2007;109(11):2229-
2238.
21. Papoulis A. Probability, Random Variables, and
Stochastic Processes. 3rd ed. New York, NY:
McGraw-Hill; 1991.
22. Gardner BG, Zietman AL, Shipley WU, Skowronski
UE, McManus P. Late normal tissue sequelae in the
second decade after high dose radiation therapy with
combined photons and conformal protons for locally
advanced prostate cancer. J Urol. 2002;167(1):
123-126.
23. Garg AK, Mai WY, McGary JE, Grant WH III, Butler
EB, Teh BS. Radiation proctopathy in the treatment
of prostate cancer. Int J Radiat Oncol Biol Phys. 2006;
66(5):1294-1305.
24. Little DJ, Kuban DA, Levy LB, Zagars GK, Pollack
A. Quality-of-life questionnaire results 2 and 3 years
after radiotherapy for prostate cancer in a random-
ized dose-escalation study. Urology. 2003;62(4):
707-713.
25. Mangar SA, Sydes MR, Tucker HL, et al; MRC RT01
Trial Management Group. Evaluating the relation-
ship between erectile dysfunction and dose received
by the penile bulb: using data from a randomised con-
trolled trial of conformal radiotherapy in prostate can-
cer (MRC RT01, ISRCTN47772397). Radiother Oncol.
2006;80(3):355-362.
26. Yeoh EE, Holloway RH, Fraser RJ, et al. Hypo-
fractionated versus conventionally fractionated radia-
tion therapy for prostate carcinoma: updated results
of a phase III randomized trial. Int J Radiat Oncol Biol
Phys. 2006;66(4):1072-1083.
27. Chen RC, Clark JA, Talcott JA. Individualizing
quality-of-life outcomes reporting: how localized pros-
tate cancer treatments affect patients with different
levels of baseline urinary, bowel, and sexual function.
J Clin Oncol. 2009;27(24):3916-3922.
28. Clark JA, Talcott JA. Confidence and uncertainty
long after initial treatment for early prostate cancer:
survivors’ views of cancer control and the treatment
decisions they made. J Clin Oncol. 2006;24(27):
4457-4463.
29. Korfage IJ, Hak T, de Koning HJ, Essink-Bot ML.
Patients’ perceptions of the side-effects of prostate can-
cer treatment–a qualitative interview study. Soc Sci
Med. 2006;63(4):911-919.
30. Yu CL, Fielding R, Chan CL. The mediating role
of optimism on post-radiation quality of life in naso-
pharyngeal carcinoma. Qual Life Res. 2003;12
(1):41-51.
31. Weinstein MC, Siegel JE, Gold MR, Kamlet MS,
Russell LB. Recommendations of the panel on cost-
effectiveness in health and medicine. JAMA. 1996;
276(15):1253-1258.
The first capacity of human intellect is that the mind
is fitted to receive the impressions made on it, either
through the senses by outward objects, or by its own
operations when it reflects on them.
—John Locke (1632-1704)
LONG-TERM OUTCOMES AFTER RADIATION FOR PROSTATE CANCER
©2010 American Medical Association. All rights reserved. (Reprinted with Corrections) JAMA, March 17, 2010—Vol 303, No. 11 1053
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 8
  • Source
    • "Thus, critics argue this study has only compared high-dose versus low-dose. However, the data remain a randomized trial comparing proton dose escalation, and further studies must still show that outcome and toxicity are comparable with photon dose escalation [16]. Future study designs must aim at comparison of these highly advanced techniques in patients with prostate cancer [21]. "
    [Show abstract] [Hide abstract] ABSTRACT: A brainstorming and consensus meeting organized by the German Cancer Aid focused on modern treatment of prostate cancer and promising innovative techniques and research areas. Besides optimization of screening algorithms, molecular-based stratification and individually tailored treatment regimens will be the future of multimodal prostate cancer management. Effective interdisciplinary structures, including biobanking and data collection mechanisms are the basis for such developments.
    Full-text · Article · Nov 2014 · Radiation Oncology
  • Source
    • "" A subsequent analysis of this multi-institutional cohort identified that rectal V70 ≥25% was associated with an inferior bowel QOL score and increased risk of fecal incontinence [15]. QOL data from the Proton Radiation Oncology Group randomized trial of 70.2 or 79.2 Gy have also been reported, using Prostate Cancer Symptom Indices [16]. Overall, there was no decline in GI or GU QOL after therapy. "
    [Show abstract] [Hide abstract] ABSTRACT: The objective of this study was to assess late toxicity and quality of life (QOL) for patients receiving definitive intensity-modulated radiotherapy (IMRT) and image-guided radiation therapy (IGRT) with regard to normal tissue sparing objectives. Three hundred and seventy-two consecutive men treated with definitive IMRT for prostate adenocarcinoma. Toxicity was graded by CTC v3.0 genitourinary (GU) and gastrointestinal (GI) toxicity at each follow-up visit. Patient-reported QOL (EPIC-26) was prospectively collected for a subset of men. Dosimetric data for bladder and rectum were compared to toxicity and QOL global domain scores, specifically analyzing outcomes for men who met ideal rectal constraints (V70 <10%, V65 <20%, V40 <40%). The median age and prescription dose was 69 years and 76 Gy, respectively. Median follow-up was 47 months. At 4 years, freedom from Grade 2 (FFG2) GI toxicity was 92% and FFG2 GU toxicity was 76%. On univariate analysis, current smoking, larger bladder volume, and higher RT dose were associated with decreased FFG2 GU toxicity, while use of anticoagulation, increasing age, and not meeting ideal rectal constraints were associated with decreased FFG2 GI toxicity (all P ≤ 0.05). Bowel QOL remained stable over the 2-year follow-up period and was higher for patients who met ideal rectal constraints (P = 0.05). IMRT with IGRT is associated with low rates of severe toxicity and a high GI and GU QOL. The use of strict rectal constraints can further improve GI QOL and reduce GI toxicity.
    Full-text · Article · Aug 2014 · Cancer Medicine
  • Source
    • "Data on prior treatment of urinary retentive and obstructive symptoms, prostatitis, and co-morbidities that might impact tolerance of radiation therapy, such as diabetes (DM), hypertension (HTN), blood, cardiovascular (CD) and chronic obstructive pulmonary (COPD) disease, smoking history, and the use of anticoagulants were extracted from patient records and histories and reported previously [3], but reviewed and confirmed for this study. Median prostate volume estimated by transrectal ultrasound at the time of fiducial-marker placement was 36.6 cm3 (range, 11.3–135.0 "
    [Show abstract] [Hide abstract] ABSTRACT: Background. To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT. Material and methods. Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78–82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively. Results. Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15–25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months. Conclusion. Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15–25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15–25).
    Full-text · Article · Apr 2013 · Acta oncologica (Stockholm, Sweden)
Show more