Shinshu Med J, 66⑵：131～137, 2018

Predictive Factors for Deterioration of Lower Urinary Tract
Symptoms After Iodine-125 Brachytherapy in Prostate Cancer Patients
Ayumu Fukazawa1）＊ , Keiichiro Koiwai1）, Takesumi Ozawa1）
Hirohide Matsushita2） and Masumi Kadoya1）
1） Department of Radiology, Shinshu University, School of Medicine
2） Department of Comprehensive Cancer Therapy, Shinshu University, School of Medicine

Purpose : To identify predictive factors for deterioration of lower urinary tract symptoms (LUTS) after iodine125 (125I) brachytherapy for prostate cancer.
Materials and Methods : 42 patients with localized prostate cancer treated with 125I brachytherapy as monother­apy between January 2013 and October 2014 were reviewed. In all patients, the prescribed dose was 160 Gy.
Patients were asked to complete the International Prostate Symptom Score (IPSS) questionnaire just before and3 months after the treatment. With an increase in IPSS ≥ 12 points defined as indicating obvious deteriorationof LUTS (ODL), we analyzed the association between ODL and the following factors : age ; total activity of thesources ; prostate volume ; and dose-volume histogram (DVH) parameters, including V150 (%) of the prostate,
V150 (cc) of the prostate, and D30 (Gy) of the urethra (minimal dose received by 30 % of the urethral volume).
Results : Seventeen (40.5%) patients developed ODL. On univariate analyses, V150 (%) and V150 (cc) were foundto be significantly associated with ODL. On multivariate analysis, only V150 (cc) was shown to have a significant
relationship with ODL (P＝0.039).
Conclusion : V150 (cc) could be a predictive factor for deterioration of LUTS after 125I brachytherapy in prostatecancer patients. Shinshu Med J 66 : 131―137, 2018
(Received for publication October 30, 2017 ; accepted in revised form December 26, 2017)
Key words : brachytherapy, lower urinary tract symptoms, prostate cancer

Ⅰ Introduction

affect sexual function. It is sometimes problematicthat EBRT requires several weeks. Brachytherapy

Permanent low-dose-rate brachytherapy is a com­

is more convenient because it takes a much shortermon treatment option for localized prostate cancer.

time than EBRT11）. However, lower urinary tract

This treatment method shows excellent long-term

symptoms (LUTS) occur more frequently after

disease control

1）-8）, especially for low-risk prostatebrachytherapy than after any other form of treat­cancer1）. Although surgical treatment and external

ment. Previous studies indicated that a large pro­beam radiation therapy (EBRT) are also common

portion of patients experienced acute LUTS after

treatment options, they have a number of draw­

brachytherapy, with 78% of patients in one study

backs. One side effect of surgical treatment is sexual

developing acute genitourinary symptoms to some9）10）

. Brachytherapy is advantageous indegree12）. The symptoms are usually manageable,

this regard, because it usually does not adversely

but they sometimes progress and therefore careful

dysfunction

observation is required13）14）. This study was per­＊Corresponding author : Ayumu Fukazawa
Department of Radiology Shinshu University School of
Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621,
Japan

formed to identify predictive factors for deteriorationof acute LUTS after iodine-125 (125I) brachytherapy
for prostate cancer patients.

E-mail : afukazawa@shinshu-u.ac.jp

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Fukazawa・Koiwai・Ozawa et al.

Ⅱ

Table 1

Materials and Methods

Our Institutional Review Board approved this ret­rospective study and waived the need for informed
consent from the patients. We usually perform

125

I

brachytherapy as monotherapy in prostate cancer
patients who fulfil the following criteria : localized
disease (T1c-T2c), Gleason score ≤ 3＋4, and PSA <10 ng/mL. The therapy is not applied in patientswith at least one of the following conditions : ex­pected not to survive > 5 years, those with a histo­
ry of pelvic irradiation or transurethral prostatec­
tomy, and prostate volume ≥ 40 mL. Between Janu‑ary 2013 and October 2014, 42 consecutive patientsselected in accordance with the above rules weretreated with 125I brachytherapy alone and were in­Patient characteristics

Age (years)†
ECOG-PS‡0
1
T stage‡
T1c
T2a
T2b
T2c
Gleason score‡
3＋3＝6
3＋4＝7
PSA level at diagnosis (ng/mL)†
Prostate volume (cc)†56－78 (65)
41
1
29
11
1
1
24
18
4.01－9.50 (5.73)
11.4－39.7 (25.6)†Range of value (median). ‡Number of patients. PSA,
prostate-specific antigen ; ECOG-PS, the Eastern Cooper­
ative Oncology Group performance status.

cluded in this study. The patient characteristics areshown in Table 1. No patients received neoadjuvant
hormonal therapy.
In brachytherapy, we employed a transperineal
approach with transrectal ultrasound guidance forpatients under spinal anaesthesia in the lithotomy
position. The prescribed dose was 160 Gy to cover ≥95% of the prostate volume. We used peripheral
loading technique with a VariSeed version 8.0 plan­ning system (Varian Medical Systems, Palo Alto, CA,

Table 2

Representative data of dosimetric analysis

Prostate V150 % (as %)†Prostate V150 % (as cc)†
Urethra D30 % (as %)†Urethra D30 % (as Gy)†

19.4－74.6 (49.9)
5.4－22.2 (12.6)
82.1－183.3 (126.4)
131.4－293.3 (202.3)†Range of value (median). Prostate V150 %, percentageof the prostate volume receiving 150 % of prescribed
dose ; Urethra D30 %, minimal dose received by 30 % of
the urethral volume.

USA) for permanently implanting the 125I radioactive
sources in the prostate. The median number ofal Prostate Symptom Score (IPSS) questionnaire

sources was 77 (range, 48－95), and the median total

according to their LUTS. This questionnaire consists

radioactivity of the implanted sources was 27.2 mCiof seven questions related to obstructive LUTS, with(range, 16.3－32.3). Alpha-1 blockers were prescribed

the score per question ranging from 0 to 5 ; an IPSS

for all patients for at least 3 months after implanta­score of 0 indicates no symptoms, while a score of 35

tion.

indicates maximal severity of symptoms. The score

Computed tomography (CT) and magnetic reso­

was divided into three levels : mild (0－7 points), in­nance imaging (MRI) were performed 1 month aftertermediate (8－19 points), and severe (20－35 points).15）

implantation. The imaging data were sent to the

We defined an increase in IPSS ≥ 12 points as obvious

same planning system as used in the implantation

deterioration of LUTS (ODL) based on the rationale

and registered to implement dosimetric analysis.

that an increase ≥ 12 points at 3 months brings pa­

The dose-volume histogram (DVH) parameters uti­

tients with mild and intermediate levels just before

lized in this study were obtained from the analysis.

implantation into a higher level.

Representative data of dosimetric analysis are shownin Table 2.

We divided the patients into two groups, i.e., thosewith ODL and those without ODL. The associations

Just before and 3 months after implantation, thebetween ODL and the following factors were ana­

patients were requested to complete the Internation­

lyzed : age (dichotomized into < 70 and ≥ 70), pros­

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Predictor of LUTS after brachytherapy
Table 3

Univariate analysis of the associations between ODL and various factors

Factors

Group with ODLGroup without ODL

P-valueAge (< 70 yrs. vs. ≥ 70 yrs.)†
Total activity of sources (mCi)‡
Prostate volume (cc)‡Prostate V150 (%)‡

13 vs. 4

18 vs. 7

0.75

26.6±4.825.7±6.2
55.1±12.725.3±4.725.5±7.747.6±15.5

0.195
0.46
0.047＊

Prostate V150 (cc)‡14.3±4.9

11.6±4.3

0.037＊Urethra D30 (Gy)‡208.2±20.5

204.3±34.1

0.32

＊

P<0.05. †Number of patients. ‡Mean±standard deviation. ODL, obvious deterioration of lower urinary tract
symptoms ; Prostate V150 %, percentage of the prostate volume receiving 150 % of prescribed dose ; Urethra D30%, minimal dose received by 30 % of the urethral volume.
Table 4
Factors
Total activity ofsources (mCi)†
Prostate volume(cc)†
Prostate V150(%)†
Prostate V150
(cc)†
Urethra D30(Gy)†Multivariate analysis of the associations between ODL and selected factors
Group with ODLGroup without ODL

P-value

Odds ratio (95 % CI)

26.6±4.825.3±4.7

0.86

1.04 (0.684－1.592)

25.7±6.2

25.5±7.7

0.059

0.58 (0.309－0.978)55.1±12.7

47.6±15.5

0.139

0.82 (0.616－1.045)

14.3±4.9

11.6±4.3

0.039＊

2.99 (1.194－10.068)

208.2±20.5

204.3±34.1

0.1220.96 (0.906－1.004)＊

P<0.05. †Mean±standard deviation. ODL, obvious deterioration of lower urinary tract symptoms ; Prostate V150%, percentage of the prostate volume receiving 150 % of prescribed dose ; Urethra D30 %, minimal dose received
by 30 % of the urethral volume.

tate volume (cc), total activity of implanted sources(mCi), prostate V150 (%, cc) (volume receiving 100%

Ⅲ

Resultsof the prescription dose), and urethra D30 (Gy) (mini­

The median IPSS just before implantation was 4

mal dose received by 30 % of the urethral volume).

points (range, 0－22), while that at 3 months after

All statistical analyses were performed with JMP

implantation was 14 points (range, 0－33). The medi­

version 11.2.0 (SAS Institute Inc., Cary, NC, USA).

an increase in IPSS during the 3-month period was

Paired t tests were performed on univariate ana­ly­

10 points. IPSS increased in 41 patients, and de­ses for all factors other than age (Chi-square test).

creased in one patient. Seventeen (40.5%) patients

We performed multivariate analysis for the factors

developed ODL. The median increase in IPSS in theselected according to the results of univariate analy­

patients with ODL was 18 points (range, 12－25).

sis. On multivariate analysis, logistic regression analy­

The results of univariate and multivariate analyses

sis was performed. Receiver operating characteristicof the association between ODL and the factors out­(ROC) curve analysis was performed to evaluate

lined above are shown in Table 3 and Table 4. On

the predictive capability for ODL of each factor that

univariate analysis, prostate V150 (%) (P＝0.047) andshowed a significant difference on multivariate analy­

prostate V150 (cc) (P＝0.037) were significantly high­sis. In all analyses, P < 0.05 was taken to indicate

er in the group with than without ODL. On multi­

statistical significance.

variate analysis, only prostate V150 (cc) was signifi­
cantly associated with ODL (P＝0.039).

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Fukazawa・Koiwai・Ozawa et al.

1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0

0.0

0.2

0.4

0.6

0.8

1.0

1-Specificity
Fig. 1

ROC curve to evaluate the predictive capability of prostate V150 (cc) for ODLThe ROC curve to evaluate the predictive capabil­
ity of prostate V150 (cc) for ODL is shown in Fig. 1.

after implantation, which seems appropriate consid­
ering the results of previous studies.

The accuracy of the prediction was moderate (areaIn the present study, prostate V150 (cc) was a pre­under the curve [AUC]＝0.66). A cut-off value of 14.7

dictive factor for deterioration of acute LUTS. Pre­cc yielded 52.9% sensitivity and 80.0% specificity to

dictive factors for acute LUTS deterioration after

predict the occurrence of ODL.

implantation have been explored in various studies.
Steggerda et al.22） reported that a dose to 0.5 cc of

Ⅳ Discussion
125

the bladder neck was correlated with acute LUTS.

I brachytherapy is accepted as a common ther­

Thomas et al.23） reported that parameters of urethral

apeutic option for localized prostate cancer due tobase (D50 and V100) were predictive of higher maxi­

its advantages over other options. However, it has

mum increase in IPSS. These results could be relat­

the drawback that some patients experience acuteed to our findings. High V150 (cc) indicates that the

LUTS after treatment. Ohashi et al.

14）

reported thatvolume of the high-dose region in the prostate is

85.4% of patients receiving 125I brachytherapy devel­

large. This mean that the high-dose region in theoped some degree of LUTS, with urinary frequency

bladder neck and the urethral base may also be

and retention being relatively common.

large. Calculation of the doses to the bladder neck

IPSS, proposed by the American Urological Asso­and urethral base may not be impossible, but it

ciation to evaluate benign prostate hyperplasia

is complicated and not reproducible. On the othersymptoms, is a useful tool to quantify LUTS and it

hand, calculating prostate V150 (cc) is simpler andhas been adopted in many studies to evaluate LUTS

more reproducible. Therefore, prostate V150 (cc)after permanent implantation of radioactive sources

could be a convenient and useful predictive factor

into the prostate. Previous reports indicated thatfor deterioration of acute LUTS. Patients with high

IPSS showed an increase after implantation with aprostate V150 (cc) should be followed up more fre­peak at 1－6 months16）-21）. We evaluated IPSS 3 months

quently and carefully in order to prevent the deteri­

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Predictor of LUTS after brachytherapy

There were some limitations in the present study.

oration of acute LUTS appropriately.
In the present study, both V 150 (%) and V 150 (cc)First, this was a retrospective study, and the popula­were significantly associated with deterioration oftion size was not large enough to yield rigorous

acute LUTS in univariate analysis, but only V 150

evidence. Second, we analyzed only patients that(cc) was significant in multivariate analysis. There

underwent 125I brachytherapy as monotherapy, andwas no significant difference in the prostate volume

therefore the results of this study cannot be applied

between patients with and without ODL, so the ab­

to patients receiving brachytherapy in combination

solute V 150 might have represented almost thewith external beam radiation therapy. Third, thesame implication as the relative V150 did in eachdefinition of ODL is arbitrary. In fact, the definitiongroup of the patients. A plausible explanation for theof the deterioration of LUTS varied among previous

result of the multivariate analysis is that susceptibili­

studies16）19）22）23）25）. This makes it impossible to com­

ty of the regions at risk described above is indepen­pare the results of these studies with each other.

dent from the prostate volume. The prostate volume

Therefore, a widely accepted consensus regarding theitself was found to be a predictive factor of acutedefinition of deterioration of LUTS is required for

LUTS deterioration in several previous studies16）20）22）

future studies.

24）
-26）

, but this was not the case in the present study.

Ⅴ Conclusion

This may have been because there were no patients

V150 (cc) could be a predictive factor for deterio­with a large prostate volume (> 40 mL) in the pres­ration of acute LUTS after 125I brachytherapy inent cohort.
Neoadjuvant hormonal therapy was also found to

prostate cancer patients. Keeping prostate V150 (cc)be a predictive factor of acute LUTS deterioration in

as low as possible should be considered in treatment

some other studies

20）
24）
27）

. The therapy causes theplanning.

prostate to shrink and deform, and there may beⅥsome difficulty in implanting radioactive sources

The authors are grateful to Mrs. I. Koiwai anduniformly into a shrunken, deformed prostate. This
may lead to an increase in prostate V150, and even­

Acknowledgements

Mrs. Y. Ogawa for technical assistance.

tually deterioration of acute LUTS.
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