Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer

Article (PDF Available)inRadiation Oncology 7(1):31 · March 2012with18 Reads
DOI: 10.1186/1748-717X-7-31 · Source: PubMed
Abstract
Background Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.
RESEARC H Open Access
Long-term biochemical results after high-dose-
rate intensity modulated brachytherapy with
external beam radiotherapy for high risk prostate
cancer
Pedro J Prada
1,3*
, Lucia Mendez
1
, José Fernández
2
, Herminio González
1
, Isabel Jiménez
1
and Elisabeth Arrojo
1
Abstract
Background: Biochemical control from series in which radical prostatectomy is performed for patients with
unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal.
The treatment regimen of HDR brachytherapy and exte rnal beam radiotherapy is a safe and very effective
treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.
Introduction
Patients with clinical stage T1c, Gleason score sum 6
tumors, and prostate-specific antigen (PSA) values < 10
ng/ml have a high likelihood of disease-free survival,
regardless of the treatment option chosen.
Nevertheless, we are faced with a great dilemma when
we seen newly diagnosed patients with high-risk pros-
tate cancer. Unfortunately, results of conventionally
accepted therapies such as radical prostatectomy and/or
standard radiotherapy have not provided these patients
with good outcomes [1-3].
The need for increased dose in patients with prostate
cancer was suggested by dose response observations by
Pollack [4,5] and Hanks [6,7].
In an effort to improve outcomes several new radia-
tion therapy strategies have been developed over the last
decade. One approach was a combination of external
beam radiotherapy (EBRT) with an intensity modulated
with high dose rate (HDR) prostate brachytherapy boost.
It has been possible to increase dose, thanks to the
brachytherapy advances, which allows for an increase in
tumour dose (boost doses greater than 125 Gy can be
safely delivered) while reducing the volume of surround-
ing normal tissue that is irradiated.
From a biologic perspective, the low prostate cancer
a/b [8] favors a large dose per fraction in terms of can-
cer control. At the same time, the a/b of the rectum
and bladder favors larger doses per fraction to increase
the therapeutic window, thus improving control while
limiting toxicity.
This study reports the long-term outcome during the
PSA era for patients with high-risk prostate cancer who
were treated with intensity modulated HDR boost.
Material and methods
Selection of patients
From June 1998 to August 2006, 252 consecutive
patients were treated for high risk clinically localized
prostate cancer with external beam radiation and inten-
sity modulated HDR brachytherapy boost.
Staging
In all cases, staging evaluation included a history and
physical examination, digital rectal palpation, serum
PSA, chest X-ray, bone scan, abdominal CT and/or
MRI, transrectal ultrasound (TRUS), and TRUS-guided
biopsy with Gleason score histologic grading. All
patients were x accor ding to the American Joint Com-
mittee on Cancer (AJCC) 4th edition [9]. Tumour char-
acteristics are shown in Table 1.
* Correspondence: pprada@telecable.es
1
Department of Radiation Oncology, Hospital Universitario Central de
Asturias, Oviedo, Spain
Full list of author information is available at the end of the article
Prada et al. Radiation Oncology 2012, 7:31
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© 2012 Prada et al; licensee BioMed Central Ltd. T his is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Excluded from the program were those patients w ho
had any of the following conditions:
- Previous radiotherapy to the pelvis
- Patients with another malignant process (except
skin tumour) 5 years before the diagnosis of the
prostate cancer
- Recurrence of prostate tumour
- Life expectancy < 5 years
Definition groups
Patients were considered high risk according to the
Memorial Sloan Kettering group definition (clinical
stage T2c or prostate-specific antigen, PSA > 20 ng/
ml or Gleason score > 7 or 2-3 intermediate-risk cri-
teria) [10].
Hormonal therapy
In our patient population, more than h alf of the
patients, 69% received hormonal ablative treatment
(LhRh agonists + antiandrogens) for one year. It was
initiated as neo-adyuvant treatment, three months
before the start of radiotherapy.
Treatment
For several years, patients diagnosed with prostate can-
cer have been treated at our Institution with EBRT
interdigitated with two intensity modulated brachyther-
apy (IMBT) HDR boosts (Table 2).
Total pelvic external beam radiation tech nique was 46
Gy delivered in 23 fractions of 2 Gy over 4.5 weeks. All
patients were treated using 18-MV photons. No external
radiation was delivered the same day o f the HDR bra-
chytherapy procedure (day 5 and 15). Total treatment
time including t he HDR boost was over a period of 5
weeks. All fields were treated daily. Isocentric techn ique
was used and all fields were equally weighted. The por-
tals used covered the prostate, seminal vesicles, and the
periprosta tic tissues with a margin of at least 1 cm. The
tumour volume was encompassed in the fields by the
100% isodose line ± 5%.
Brachytherapy procedures were done under spinal
anesthesia. The dose administered in each application
was 11.5 Gy, except in the first group of patients treated
(17%) in whom the dose applied varied between 10.5
and 11. The target volume of the implant was the pros-
tate gland + 5 mm peri-prostatic area and medial
aspects of seminal vesicle. All patients were discharged
from the center the same day of the procedure between
6-8 hours of implantation.
The total combined BED dose ranged from 292 Gy to
366 Gy based upon a a/b ratio of 1.2 [8].
Toxicity
Patients were followed with symptom assessment and
PSA determinations every 3 months for the first year,
every 6 months for the second year and yearly
thereafter.
Toxicity was reported according to the Common
Toxicity Criteria for Adverse Event, Version 4.0 (CTAE
v4.02) by the National Cancer Ins titute. Chronic toxicity
was defined as those symptoms which persisted or pre-
sented beyond 6 months. Potency was defined as the
Table 1 Patient and tumor characteristic (n = 252)
Characteristics Patients (%)
Stage
T2a 36 (14%)
T2b 58 (23%)
T2c 158 (63%)
Geason score:
6 109 (43%)
= 7 77 (31%)
> 7 66 (26%)
Pretreatment PSA (ng/ml)
10 44 (17%)
10.1-20 101 (40%)
> 20 107 (43%)
Mean:20/Median 18 (2.05-59.60)
Adjuvant hormonal ablation
Yes 173 (69%)
No 79 (31%)
Age at diagnosis (yr)
60 32 (13%)
61-70 131 (52%)
> 70 89 (35%)
Risk Level
High Risk by Gleason y/o PSA 187 (74%)
High Risk by T 65 (26%)
No. Prognostic factors
2 intermediate Risk Criteria 44 (17%)
1 High Risk Criteria 100 (40%)
2 High Risk Criteria 89 (35%)
> 2 Risk Criteria 19 (8%)
Gland Vol. Implant (cc): Mean:34/Median 31 (9-87)
Table 2 Treatment scheme
Weeks External radiotherapy Brachytherapy
1st week 2 Gy/day × 4 days 1st HDR; 5th day (11.5 Gy)
2nd week 2 Gy/day × 5 days No
3rd week 2 Gy/day × 4 days 2nd HDR; 15th day (11.5 Gy)
4th week 2 Gy/day × 5 days No
5th week 2 Gy/day × 5 days No
Total dose 46 Gy/23 sessions 23 Gy/2 sessions
HDR = high dose rate (brachytherapy)
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ability to achieve an erection that was sufficient for
intercourse.
Toxicity and sexual side-effects w as scored by the
physician.
Statistical considerations
Distant metastatic disease was defined by an imaging
study or physical examination that demonstrated can-
cer outside of the prostate and its regional nodes. Fail-
ure in cause-specific survival (CSS) analyses was
defined as death due to prostate can cer. Failure in
tumour-free survival (TFS) analyses w as represented as
detection of local and/or systemic tumour relapse, and
bNED for no clinical and biochemical evidence of dis-
ease. Overall survival reflected all deaths, cancer-
related or otherwise. To assess t he local relapse, sex-
tant prostate biopsies were taken in patients with no
metastatic disease if they did not refuse this procedure.
Biochemical failure was defined according to the
Phoenix definition [11] consensus panel statement.
Estimated likelihood of events was calculated by the
Kaplan-Meier method from the time of completion of
radiotherapy. The statistical significance of the differ-
ence between estimated event-free
Curves were calculated with the long-rank test. Multi-
variate analysis was performed using the Cox propor-
tional hazards model [12]. Statistical analyses were
performed with SPSS version 17.0 (SPSS Inc, Chicago,
IL).
Results
Clinical characteristics
All patients treated in the protocol were included for
analysis and completed the planned course of radiation.
All patients have been seen in follow up.
The high risk group, as defined in this study, repre-
sented 100% of the patient population (74% were high
risk by Gleason and/or PSA and 26% by T-stage) (Table
1).
The median V100, V90, V150 and V200 (% volume of
CTV receiving 100% of prescription dose) we re respec-
tively 93.73% (96.82-85.81), 97.90% (99.80-91.79%),
21.02% (38.17-12.64) and 5.97% (9.41-3. 30). The median
D90(Thedosethatcovers90%volumeofCTV)was
12.04 Gy (18.38-9.45). Maximum urethral point dose
was 12.66 Gy (16.36 Gy-9.25 Gy) and maximum rectal
point dose was 9.56 Gy (14.09 Gy-8.2 Gy).
Oncologic endpoints
Of all 252 patients, 51 had evidence of biochemical
relapse, 42 had clinical relapse and 12 died from pros-
tate cancer; 35 patients died of other illnesses. Mean
and median follow-up for all patients were 77 and 74
months respectively with a range of 12 to 142 months.
In the 51 patients with a biochemical failure, the med-
ian time to PSA failure was 38 (5-80) months, with 55%
failing within 3 years and 98% within 6 years. In patients
with no biochemical failure, the mean and median PSA
level after treatment was 0.10 and 0.03 (0.0-1.2) ng/ml,
the last follow-up PSA levels were 0.2 ng/ml in 90%, <
1 ng/ml in 99.6% and 1.2 ng/ml in a patient.
The 5 and 10 years for biochem ical control wer e 84%
and 78% (SD ± 2%), whereas in tumor-free survival
(TFS) they were 86% and 82% (SD ± 2%) at 5 and 10
years respectively. The 10 year cause specific survival
was 93% (SD ± 2%) with 99% (SD ± 1%) of patients
being free of local recurrence. T he overall survival
according to Kaplan-Meier estimates was 88% and 78%
(SD ± 4%) at 5 and 10 years respectively (Figure 1).
Characteristics used for multiple regression analyses to
correlate with biochemical failure were: clinical T-classi-
fication, Gleason score, pretreatment PSA, age, bra-
chytherapy dose level, pros tate volume and hormonal
ablative treatment.
The multivariate Cox regression analyses identified,
Gleason score as independent prognostic factors for bio-
chemical failure.
The 10-year actuarial biochemical control stratified by
Gleason score was 85%, 72% and 74% for patients with
Gleason score of 6, 7 and > 7, respectively (P = 0.039)
(Figure 2).
The 10-year actuarial biochemical control was 89% for
patients with two intermediate risk c riteria, 80% wit h
one high risk criteria and 72% for patients with 2-3 high
risk criteria (P = 0. 04) (Figure 3).
The 10-year actuarial biochemical control in patients
classified as high risk only by Gleason and/or PSA, no
by T-stage, w as 86% for patients with two intermediate
risk cr iteria, 73% with one high risk crite ria and 71% for
patients with 2 high risk criteria (P = 0. 45) (Figure 4).
Mean age was 67 years (range 49-78). The actuarial
analysis of biochemical control at ages less than 60, 60
to 69 and greater than 69 years demonstrated no signifi-
cant difference. As younger and older pa tients benefited
equally (P = 0.148).
The actuarial biochemical control was 80% and 74% (P
= 0.173), in patients who received hormones and in
those who did not.
All other variables (pretreatment PSA P = 0.898, T-
classification (p = 0.273), brachytherapy dose level P =
0.492, and volu me P = 0.6 15) were stati stical no signifi-
cant for biochemical failure.
Metastatic disease developed in 42 patients and the
distant metastatic rate at 10-years was 14%. Multivariat e
analysis showed that Gleason score was the only factor
to significantly affect distant metastases, with 10-year
rates of 7%, 21% and 17% for scores of 6, 7 and > 7,
respectively (P = 0.014).
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The 10-year actuarial tumour-free survival (TFS) was
90%, 73% and 78% for pati ents with Gleason sc ores of
6, 7 and > 7, respectively (P = 0.020).
Acute and chronic urinary toxicity
Moderate increase in urinary frequency and tract pain
(urethritis) occurred at the end of the treatment. At 6
month genitourinary grade I toxicity was 6% (increase in
urinary frequency and dysuria. Moderate symptoms).
Acute grade 1 urinary retention requiring a temporary
post-implant bladder catheter was seen in 4 (1.6%)
patients.
Grade 4 or 5 late toxicity was not detected in any
patients. Thirteen patients (5%) showed, increase in
urinary frequency and dysuria at 12 month.
A urethral stricture after treatment was observed in
seven patient s (2.7%). Four patients required intermit-
tent bladder catheterization and endoscopic urethrot-
omy was required in three patients.
No patients reported incontinence after treatment.
Gastrointestinal toxicity
Acute gastrointestinal toxicity grade II was 3%, consist-
ing in increase of 4-6 stools per day over baseline and
mucus in stool, n o patients developed grade 3 toxicity.
At six months gastrointestinal grade II toxicity was 1.6%.
At 12 months 99% of patients reported no change in
bowel function. Intermittent rectal bleeding without sys-
temic repercussions was reported in 5 patients (2%). No
patients with perineal pain were reported.
Figure 1 Actuarial analysis of all 252 patients for Cause specific survival, tumor-free survival, biochemical control and overall survival.
Figure 2 Actuarial analysis of biochemical control by Gleason score. P value generated from Log-Rank.
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Sexual function
Of the 131 (52%) patients who were potent preopera-
tively and h ormonal manipulation was not used, 72%
were potent postoperatively but only 68% the patients
were potent when hormonal manipulation was used.
Potency was defined as the ability to achieve an erection
that was sufficient for intercourse.
Correlation between post implant dosimetry and toxicity
Characteristics used for multiple logistic-regression ana-
lyses which correlates probability of acute and chronic
urinary toxicity were: pre-treatment prostate volume,
year of implant, number of needles implanted,
brachytherapy dose, hormonal ablative treatment, maxi-
mum urethral dose.
The multivariate logistic-regression analyses showed
than patients with high urethral dose after established
brachytherapy technique are more likely to suffer acute
urethritis (P = 0.018).
Discussion
The importance of dose escalation, has been well docu-
mented, high radiation doses improve biochemical and
clinical results for prostate cancer patients [4-7]. Kuban
et al. rep orted an improvement in bioche mical control of
78% for doses of 78 Gy, vs 59% for the 70 Gy arm [13].
Figure 3 Actuarial analysis of biochemical control by poor prognostic factors groups. P value generated from Log-Rank.
Figure 4 Actuarial analysis of biochemical control by poor prognostic factors groups in patients classified as high risk only by
Gleason and/or PSA, no by T-stage. P value generated from Log-Rank.
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The combination of EBRT and HDR brachytherapy
allows the delivery of very high biologic equivalent
doses to the prostate not achievable by intensity modu-
lated treatments (IMRT) with image guided adaptive
radiotherapy (IGART) techniques.
Based on these principles, since June 1998 we have
been performing High dose rate brachyther apy boost for
prostate cancer.
The high risk group in our report represented 100% of
the patient population and the results of this combined
therapy (EBRT + HDR boost) at 10-years are promising,
with a biochemic al control rate of 78%, cause specific
survival of 93%, overall survival of 78%, and freedom
from distant metastases of 86%. The 10-year actuarial
biochemical control in patients classified as high risk
onlybyGleasonand/orPSA,nobyT-stage,was86%
for patients with two intermediate risk criteria, 73% with
one high risk criteria and 71% for patients with 2 high
risk criteria.
The results presented here for high risk group of
patients, are superior to the series on radical prostatect-
omy and standard radiotherapy therapies published in
the literature.
The Memorial Sloan Kettering reported in unfavorable
risk cases 5-year PSA relapse-free survival rate for 81 Gy
the 67% versus 43% for 75.6 Gy and 21% for 64.8 to
70.2 Gy [14].
Hanks et al. observed that patients with unfavorable
disease (Gleason 8andPSA 20 ng/ml) treated with
three-dimensional conformal radiation therapy (3D
CRT) a dose of 76 Gy achieved only 26% in the 5-year
PSA relapse-free survival rate [15]. Dearnaley et al.,
Sathya et al. and Zietman et al. reported similar results
[16-18].
Our study shows an advantage to high-dose over con-
ventional-dose conformal radiation in terms of freedom
from biochemical failure for men with high risk prostate
cancer.
Similar observations were reported by other institu-
tions using conformal high dose rate brachytherapy.
Martinez et al. [19] reported 5-year actuarial biochem-
ical control rate of 85% for patients with 1 poor prog-
nostic factor, 75% for 2 and 50% for all 3. Galalae et al.
reported 8-year bNED survival rate (free of clinical or
biochemical evidence of disease) in the high-risk prog-
nostic group of 64% [20]. Dattoli et al. [21] and Mate et
al. [22] reported similar results. A recent report Stock et
al. reported 8-year actuarial biochemical control rate of
73% for patients with Gleason score 8-10 prostate can-
cer [23].
On the other hand, surgery is not the best treatment
for high risk patients. Catalona et al. [24] Studied 3478
men with tumors of clinical stages T1-T3 N0 M0
followed for an average of 65 months after radical retro-
pubic prostatectomy. Actuarial 10-year biochemical pro-
gression-free probabilities were 59% for cT2b-c, 15% for
cT3 disease and 50% for Gleason sum 4 + 3 and 32%
for Gleason 8-10 disease. Actuarial 10-year biochemical
progression-free probabilities were 49% for PSA greater
than 10 ng/ml.
The Johns Hopkins group reported similar results
[25,26]. Kermen and Mi les [27] reported a 5-year bNED
rate of 54% after radical prostatectomy. Surgery results
of Multi-institutional pooled analysis in men with locally
advanced prostate cancer [2] published a 2.2-year of bio-
chemical control rate of 16%.
The Memorial Sloan Ketteri ng Center group analyzed
the oncologic outcome after laparoscopy radical prosta-
tectomy, 8-year probably of freedom from progression
for high risk cancer was 53% [28].
In patients with high risk prostate cancer, the 10-year
biochemical control was 16-54% for prostatectomy trea-
ted patients compared to 86-71% for our combined con-
formal EBRT with HDR boost.
Despite the wide diffusion of laparoscopic radical
prostatectomy and robot-assisted laparoscopic radical
prostatectomy, only few studies comparing the results of
these techniques with the retropubic radical prostatect-
omy. The systematic review of the literature performed
by Ficarra et al. [29], were not sufficient to prove the
superiority of any surgical approach in terms of func-
tional and oncologic outcomes.
Gleason score was in our paper the most significant
predictor of biochemical failure and developing distant
metastases. Other gro ups reported similar results
[19,21,23].
Hormonal ablative treatment did not improved the
outcome in the present analysis, this corrob orate the
findings of previous studies [21,30,31]. All prospective,
randomized trials show a positive outcome of adding
hormonal therapy [32-34] but these studies were done
with low radiation doses (68-70 Gy), the BED equivalent
of 70 Gy was 129 Gy, much lower than BED in our ser-
ies (BED dose ranged from 292 Gy to 366 Gy).
The low toxicity observed in our series, despite the
high radiation doses delivered, was the result of carefully
executed real-time brachytherapy technique [35]. Urin-
ary and Gastrointestinal complications rates were in
concordance with the experience of other institutions
using conforma l high doses rate brachytherapy [19-22]
and favourably with other 3-D conformal radiotherapy
escalating series [14,15].
The cause specific survival at 10-year of 93% and bi o-
chemical control of 78% demonstrate the effectiveness
of the described radioth erapy regime and the high cura-
tive potential of this therapy protocol.
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Conclusions
The present studies shows that when men with high risk
clinically localized prostate cancer are treated with
EBRT interdigitated with two HDR Ir-192 brachytherapy
boost, allows us to administer the highest possible dose
totheprostateandthelowestdosetothesurrounding
healthy structures, achieved excellent results in terms of
local and bio chemical control, decrease the toxicity and
the overall treatment time by at least 3 weeks compared
to 3-D conformal radiation therapy and intensity
modulated.
In summary this treatment regimen is a safe and very
effective for patients with high risk localized prostate
cancer and repre sents a consi derable improvement over
standard surgical and radiotherapy modalities.
Abbreviations
AJCC: American Joint Committee on Cancer; BED: Biologically effective dose;
BTm: Brachytherapy; bNED: No clinical and biochemical evidence of disease;
CTV: Clinical target volume; CSS: Cancer specific survival; CT: Computed
tomography; D90: The dose that covers 90% volume of CTV; 3D CRT: Three-
dimensional conformal radiation therapy; EBRT: External beam radiotherapy;
GU: Genitourinary; HDR: High dose rate; IMRT: Intensity modulated
radiotherapy; IGART: Image guided adaptive radiotherapy; PSA: Serum
prostate-specific antigen; PTV: Planning target volume; CTAE v4.02: Common
Toxicity Criteria for Adverse Event, Version 4.0 by the National Cancer
Institute; SPSS: Statistical analysis SPSS; SD: Standard desviations; TFS:
Tumour-free survival; TRUS: The trans-rectal ultrasound; V100, V90, V150 and
V200: (% volume of CTV receiving 100% of prescription dose).
Author details
1
Department of Radiation Oncology, Hospital Universitario Central de
Asturias, Oviedo, Spain.
2
Department of Radiation Physics, Hospital
Universitario Central de Asturias, Oviedo, Spain.
3
Department of Radiation
Oncology, Hospital Central de Asturias, C/Julian Claveria s/n, Oviedo 33006,
(Asturias), Spain.
Authors contributions
PJP: conception and design. LM acquisition of data. JF analysis of data. HG
revising references. IJ alignment and drafted the manuscript. EA acquisition
of data. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 18 December 2011 Accepted: 7 March 2012
Published: 7 March 2012
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doi:10.1186/1748-717X-7-31
Cite this article as: Prada et al.: Long-term biochemical results after
high-dose-rate intensity modulated brachytherapy with external beam
radiotherapy for high risk prostate cancer. Radiation Oncology 2012 7:31.
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    • "[33, 34] The predicted HALE for 2013 was higher compared to 13.8 years reported for Canadian men in 2005/2007. [35] The model predicted survival at 5-and 10-year was comparable to contemporary studies.3637383940414243 Study findings corroborated with the evidence that contemporary management options conferred improved survival. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Prostate cancer (PCa) is the most common non-skin cancer among men in developed countries. Several novel treatments have been adopted by healthcare systems to manage PCa. Most of the observational studies and randomized trials on PCa have concurrently evaluated fewer treatments over short follow-up. Further, preceding decision analytic models on PCa management have not evaluated various contemporary management options. Therefore, a contemporary decision analytic model was necessary to address limitations to the literature by synthesizing the evidence on novel treatments thereby forecasting short and long-term clinical outcomes.
    Full-text · Article · Dec 2014
    • "Prospective randomized trials have demonstrated the advantage of dose-escalated radiotherapy in the treatment of localized prostate cancer123 . Despite the implementation of new radiotherapy technologies, such as intensity modulated radiation therapy and image guided radiation therapy, rectal toxicity has remained high, thus limiting dose escalation45678 . "
    [Show abstract] [Hide abstract] ABSTRACT: Background and purpose Rectal toxicity presents a significant limiting factor in prostate radiotherapy regimens. This study evaluated the safety and efficacy of an implantable and biodegradable balloon specifically designed to protect rectal tissue during radiotherapy by increasing the prostate–rectum interspace. Patients and methods Balloons were transperineally implanted, under transrectal ultrasound guidance, into the prostate–rectum interspace in 27 patients with localized prostate cancer scheduled to undergo radiotherapy. Patients underwent two simulations for radiotherapy planning--the first simulation before implant, and the second simulation seven days post implant. The balloon position, the dimensions of the prostate, and the distance between the prostate and rectum were evaluated by CT/US examinations 1 week after the implant, weekly during the radiotherapy period, and at 3 and 6 months post implant. Dose-volume histograms of pre and post implantation were compared. Adverse events were recorded throughout the study period. Results Four of 27 patients were excluded from the evaluation. One was excluded due to a technical failure during implant, and three patients were excluded because the balloon prematurely deflated. The balloon status was evaluated for the duration of the radiotherapy period in 23 patients. With the balloon implant, the distance between the prostate and rectum increased 10-fold, from a mean 0.22 ± 0.2 cm to 2.47 ± 0.47 cm. During the radiotherapy period the balloon length changed from 4.25 ± 0.49 cm to 3.81 ± 0.84 cm and the balloon height from 1.86 ± 0.24 cm to 1.67 ± 0.22 cm. But the prostate-rectum interspace distance remained constant from beginning to end of radiotherapy: 2.47 ± 0.47 cm and 2.41 ± 0.43 cm, respectively. A significant mean reduction in calculated rectal radiation exposure was achieved. The implant procedure was well tolerated. The adverse events included mild pain at the perineal skin and in the anus. Three patients experienced acute urinary retention which resolved in a few hours following conservative treatment. No infections or thromboembolic events occurred during the implant procedure or during the radiotherapy period. Conclusion The transperineal implantation of the biodegradable balloon in patients scheduled to receive radiotherapy was safe and achieved a significant and constant gap between the prostate and rectum. This separation resulted in an important reduction in the rectal radiation dose. A prospective study to evaluate the acute and late rectal toxicity is needed.
    Full-text · Article · Apr 2013
    • "External beam radiotherapy (EBRT) and temporary interstitial brachytherapy (HDR-BT) are all well established radiotherapy (RT) techniques for a curative treatment of localized prostate cancer1234567. The combination with hormonal therapy (HT) has been shown to be associated with improved overall survival for high risk patients after EBRT in several prospective randomized studies89101112. "
    [Show abstract] [Hide abstract] ABSTRACT: The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000–2004 either using external-beam RT (EBRT; 70.2Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18Gy + 50.4Gy; n=71). The median follow-up period after RT was 68 months. Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT). Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings.
    Full-text · Article · Dec 2012
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