Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer
Hatiboglu et al. BMC Urology
Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer
I. V. Popeneciu
D. Teber 0
S. Pahernik 0
0 Equal contributors Department of Urology, University of Heidelberg , Im Neuenheimer Feld 110, 69120 Heidelberg , Germany
Background: To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer. Methods: One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQPR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification. Results: One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58. 6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69. 4%. Conclusion: HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not suitable for standard treatment.
HIFU; Quality of life; Outcome
High intensified focused ultrasound (HIFU) is a minimal
invasive, thermoablative treatment option for patients
with localized prostate cancer. Its aim is equivalent
oncological safety with reduced toxicity, compared to
standard treatment options . HIFU can be performed
in general or spinal anesthesia via transrectal approach.
Focused, high energetic ultrasound waves cause thermal
alteration and cavitation, causing coagulative necrosis
and thereby destroying malignant tissue [2, 3].
Since the initial presentation in 1995 , several
studies have evaluated oncological and functional outcome
after HIFU. Recent publications report of 76%, 63% and
57% biochemical free survival after 8 years for low-,
intermediate- and high-risk patients . The 10-year
prostate cancer specific survival rate and metastasis-free
survival rate were 97% and 94%, respectively .
Regarding morbidity of HIFU treatment, severe incontinence
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rates of 3.1% and erectile function preservation of up to
42.3% are described . Patients rejecting standard
treatment and preferring HIFU do this with the expectation
for less complications and less invasiveness compared to
standard treatment. Especially incontinence, erectile
dysfunction after radical prostatectomy as well as
gastrointestinal and genitourinary side effects after
radiotherapy are feared by many patients and can impair their
quality of life . Recent studies have evaluated quality
of life for prostate cancer patients after local therapy,
showing good results with moderate alteration in erectile
and lower urinary tract function with minimal decrease
in quality of life [7, 8]. The authors utilized standardized
questionnaires for this evaluation like the European
Organisation for Research and Treatment of cancer
(EORTC) quality of life questionnaire QLQ-C30 and the
prostate specific module QLQ-PR25. The QLQ-C30
questionnaire evaluates overall health related quality of
life as well as several functional domains and general
cancer related symptoms. The QLQ-PR25 assesses
urinary symptoms, sexual activity and function, as well as
bowel symptoms. Both questionnaires have been
evaluated and validated extensively [9, 10]. Regarding quality
of life for prostate cancer patients, both questionnaires
are routinely used.
To our knowledge, data about quality of life after
HIFU therapy using standardized questionnaires are rare
and have not been evaluated in a standardized fashion
so far. The aim of the study was to investigate
prospectively quality of life after HIFU ablation of the prostate
for the local treatment of prostate cancer.
One hundred thirty-one patients undergoing infravesical
desobstruction and HIFU treatment for localized
prostate cancer between 02/2008 and 12/2012 were followed
up in a prospectively conducted database. The study
protocol was approved by the ethics committee of the
University of Heidelberg (S-182/2012). All patients gave
written informed consent.
All patients were treated with the Ablatherm HIFU
device (Ablatherm integrated imaging device; EDAP-TMS,
Vaulx-en-Velin, France). Before HIFU treatment an
infravesical desobstruction was routinely done one day
prior to HIFU treatment, normally by transurethral
resection of the prostate (TURP) or by greenlight
laservaporisation of the prostate . The mode of infravesical
desobstruction was at patients’ preference (TUR-P was
recommended, some patients explicitly wished to
undergo greenlight laservaporisation). HIFU treatment
was performed as inpatient procedure in combined
spinal and epidural anesthesia. Nervesparing procedure
was only done in patients explicitly demanding for this.
All these patients were intensively informed about
higher risk for recurrent prostate cancer but wished to
undergo nervesparing anyway and with awareness of all
risks (this was also documented in informed consent). In
these cases, mainly one sided nervesparing was done - if
prostate biopsy showed cancer infiltration on only one
side the nervesparing was done on the contralateral side.
However, some patients explicitly wished both sided
nervesparing, taking into account the risk for tumor
recurrence. For all patients, the following parameters
were assessed and entered in a prospective conducted
database: patient age, body mass index, prostate volume,
PSA value at diagnosis, Gleason Score, clinical stage,
risk classification (according to D’Amico et al. [12, 13]),
PSA nadir and time to PSA nadir, biochemical
recurrence according to Stuttgart criteria  and Phoenix
criteria . In addition, treatment related data were
evaluated and included: type of preoperative infravesical
desobstruction, duration and number of applied lesions during
HIFU treatment, nervesparing (non-,unilateral-,bilateral
nervesparing), hospital stay, indwelling time for
transurethral and suprapubic catheter, uroflowmetry and
residual volume (pre-HIFU and 2 weeks post-HIFU). In
addition, complication were evaluated according to
Clavien-Dindo . Patients were asked to fill out the
international prostate symptom score (IPSS) and
international index for erectile function (IIEF-5)
questionnaire before and 3 months after HIFU treatment.
Continence was evaluated and graduated during
followup, the usage and number of used pads was evaluated.
Patients were also asked for sexual activity after HIFU
treatment including the usage of adjuvant medication
Assessment of quality of life
All patients were asked to complete the European
Organisation for Research and Treatment of cancer
(EORTC) quality of life questionnaire QLQ-C30
(Version 3.0) and the prostate specific module QLQ-PR25
retrospectively in 12/2012. Both questionnaires are
internationally validated and used in cancer patients. They
were used in German translation. The QLQ-C30
questionnaire consists of 30 questions, the QLQ-PR25 of 25
questions. The QLQ-C30 measures global health related
quality of life, five functional domains (physical, role,
emotional, cognitive and role function) and nine
symptom scales (fatigue, nausea and vomiting, pain, dyspnoe,
insomnia, appetite loss, constipation, diarrhea, financial
difficulties). The QLQ-PR25 questionnaire, consisting of
25 questions, assesses urinary symptoms, bowel
symptoms, treatment-related symptoms and sexual symptoms
and functioning. In both instruments, all answers ranged
from 1 (not at all) to 4 (very much), despite 2 questions
in the QLQ-C30 considering global health related
quality of life ranging from 1 (very poor) to 7 (excellent).
Both questionnaires have been interpreted according to
the EORTC guidelines. The scores have been converted
to linear scales ranging from 0 to 100. Higher values in
functional scales and health related quality of life
represent better results. Lower values in symptom scales
represent less symptoms.
Above mentioned variables were evaluated by descriptive
statistics. Median, mean, standard deviation and range
were calculated for every variable using Microsoft Excel
and IBM SPSS statistics version 20.
One hundred thirty-one patients with a mean age of
72.8 ± 6.0 years have been included to this analysis. PSA
values at prostate cancer diagnosis were 9.6 ± 14.9 ng/
ml. Gleason score was 6 in 57 patients (43.5%), 7 in 66
patients (50.4%) and ≥ 8 in 8 patients (6.1%). 29.0% of
patients had a low risk, 58.8% an intermediate risk and
12.2% a high risk prostate cancer (Table 1). When
presenting for HIFU treatment, 28 patients (21.4%) have
been on neoadjuvant hormonal therapy, that has been
stopped directly after HIFU treatment. Bothsided
nervesparing was performed in 21.1%, 9.6% and 6.7%,
onesided nervesparing in 28.9%, 26.0% and 6.7% of low-,
intermediate- and high-risk patients, respectively. After
HIFU the mean PSA nadir was 0.6 ± 1.2 ng/ml (median:
0.1 ng/ml; range 0.01-6.50 ng/ml) and reached after
4.7 months (SD: 5.7) (Table 2). Mean follow up was
22.2 months (SD: 16.1). 28 patients (21.4%) developed a
biochemical recurrence, defined as PSA Nadir + 1.2 ng/
ml (according to Stuttgart criteria ) after a mean
Table 1 Demographics
Risk stratification (D’Amico)
Prostate volume (ml)
Prostate volume after resection
Table 2 Perioperative parameter
Treated HIFU volume (ml)
Duration of HIFU treatment (minutes)
Transurethral catheter indwelling time
Suprapubic catheter indwelling time
time of 15.5 ± 11.6 months. Among them, 10 patients
(26.3%), 12 patients (15.6%) and 6 patients (37.5%) of
low-, intermediate-and high-risk profile, respectively.
Therefore, biochemical recurrence free survival was
73.7%, 84.4% and 62.5% for low-, intermediate- and
high-risk patients at latest follow-up. In addition, 3
patients had histological confirmed recurrence that was
confirmed in prostate biopsy in patients undergoing
biopsy after 6 months at own wish or after bladder neck
resection due to infravesical obstruction.
Of these 31 patients with recurrent prostate cancer, 18
patients (58.1%) underwent active therapy. Twelve of
these patients were lost to follow-up. Five patients
underwent salvage radiotherapy, two 2 patients
salvageHIFU therapy, one patient prostatectomy and one
patient brachytherapy and pelvic lymphadenectomy. The
other 9 patients (29.0%) did not wish salvage therapy
and received antiandrogen treatment. During follow-up,
7 patients (5.3%) deceased – 1 patient because of
systemic progression of the prostate cancer, the other 6
patients due to cardiovascular events (Table 3).
When defining biochemical recurrence according to
Phoenix criteria, 20 patients (15.5%) showed biochemical
recurrence with a mean time to recurrence of 17.4 ±
12.5 months. Biochemical recurrence free survival was
therefore 81.6%, 89.6% and 68.8% for low-,
intermediateand high-risk patients at latest follow-up, respectively.
Regarding treatment data, 109 patients (83.2%)
underwent TUR-P, 18 patients greenlight-laser vaporization
(13.7%) and 1 patient (0.8%) combination of both in
advance to HIFU treatment. Resection was done the day
prior to HIFU. Mean prostate size was thereby reduced
from 43.7 ml (±25.6) to 26.0 ml (±12.5). Three patients
(2.3%) had no prior infravesical desobstruction. During
HIFU treatment, a one-sided nervesparing was done in
31 patients (23.7%), a both sided nervesparing in 16
patients (12.2%). Perioperative side effects up to 30 days
after HIFU treatment were assessed and grouped
according to Clavien-Dindo classification and occurred in
Table 3 Oncological outcome
PSA – nadir (ng/ml)
Time to nadir (months)
Biochemical recurrence (BCR)
low - risk - PCa
intermediate - risk – PCa
high - risk – PCa
Time to BCR (in months)
Time to BCR (in months)
low - risk - PCa
intermediate - risk - PCa
high - risk – Pca
Recurrence without BCR
25 patients (19.1%), 4 patients had 2 complications.
Main complications were infravesical obstruction and
urinary tract infections. With respect to infravesical
obstruction, grade II and grade IIIa complications occurred
in 14 (10.7%) and 15 (11.5%) cases, respectively.
Regarding late complications beyond 30 days, 47 patients
(35.9%) needed further treatment. 46 patients (35.1%)
needed catheterization or suprapubic catheter insertion
and transurethral resection because of bladder neck
obstruction. One patients needed DJ insertion because
progression of prostate cancer.
IPSS score before and after HIFU treatment was 10.9
± 7.1 and 9.2 ± 6.2, respectively. Uroflowmetrie before
and after HIFU treatment showed max. flow of 14.0 ml/
s (SD 8.2) and 14.1 ml/s (SD 8.7) with post voiding
residual volume of 45.5 ml (SD 69.4) and 54.0 ml (SD
93.6), respectively. Regarding incontinence, 14.3%, 2.9%
and 0% of patients had de novo urinary incontinence
grade I°, II° and III° and 3.8% urge incontinence due to
HIFU treatment. Before HIFU treatment 97.1% of
patients did not need a pad. After HIFU treatment, 9.5%,
6.7% and 1.9% of patients needed 1pad, 2pads or >2pads,
respectively, meaning 81.9% did not need a pad at all at
IIEF-5 scores showed 17.2 ± 7.3 and 9.7 ± 8.0 before
and after HIFU treatment in all patients, respectively.
When grouped according to nervesparing procedure,
mean IIEF-5 score before and after HIFU was 15.1 ± 8.1
vs. 7.5 ± 7.4 for the non-nervesparing group, 19.7 ± 4.8
vs. 12.5 ± 8.3 for the one-sided nervesparing group and
20.7 ± 5.3 and 12.1 ± 7.5 for the both sided nervesparing
group, respectively. Regarding the ability to have sexual
intercourse, 15.8%, 58.6% and 66.7% of patients after non-,
onesided and bothsided nervesparing procedure were able
to obtain sufficient erection for intercourse, respectively.
33.3% of these patients used PDE5 inhibitors, 3 patients
mechanical devices to obtain erection. Functional
outcomes after HIFU therapy are displayed in Table 4.
Quality of life was evaluated using the QLQ-C30
questionnaire and showed a global health status of 69.4%
(SD: 20.6). Functional scales revealed physical
functioning of 86.2% (SD 17.7) after HIFU treatment. Regarding
symptom scales, fatigue and insomnia were the most
frequent symptoms with 25.9% (SD: 24.8) and 31.4% (SD:
31.4) of cases in a cohort of men aged 72.8 ± 6.0 years.
For further evaluation of prostate specific symptoms the
QLQ-PR25 questionnaire was used and showed sexual
activity and functioning of 56.9% (SD: 28.1) and 49.6%
(SD: 20.5), respectively. Evaluation of symptom scales
showed urinary symptoms in 28.3% (SD: 18.4) and
Table 4 Functional outcome after HIFU treatment (mean(SD))
Continence and micturation symptoms
Micturation volume (ml)
Post voiding Residual volume(ml)
Incontince grade II°
Incontince grade III°
Sexual intercourse after HIFU
Due to HIFU treatment
IIEF - 5 - non – nervesparing
IIEF - 5 - onesided - nervesparing
IIEF - 5 - bothsided – nervesparing
urinary bother in 38.6% (SD: 35.6) of patients after
HIFU. Bowel symptoms did appear in 6.7% (SD: 11.2) of
patients. The overall quality of life did not change before
and after HIFU (evaluated by the IPSS questionnaire).
All results are displayed in Table 5.
The present study was performed to evaluate quality of
life after HIFU treatment for prostate cancer. To our
knowledge, this is the first study investigating this topic.
Quality of life was assessed by standardized
questionnaires. In addition, functional outcome and oncological
results were evaluated with respect to limited followup.
Regarding oncological results, recent reports from
Crouzet et al. showed 7 years biochemical free survival
Table 5 Quality of life – post-HIFU outcome of QLQ-C30,
QLQPR25 and IPSS-QoL questionnaires (n = 105). Data are shown as
mean with standard deviation
(Phoenix Criteria) in 75%, 63% and 62% for low-,
intermediate- and high-risk prostate cancer patients .
Using the recently supposed stricter Stuttgart criteria
(meaning PSA nadir +1.2 ng/ml ), Pfeiffer et al.
described 5 years biochemical free survival as 85%, 65%
and 55% for low-, intermediate- and high-risk prostate
cancer . The present series mainly consisted of
intermediate risk patients (58.8%) because high risk patients
were consulted for standard treatment and low risk
patients for active surveillance. In this cohort, biochemical
recurrence free survival was 76.3%, 84.4% and 64.7%
(using Stuttgart criteria) and 81.6%, 89.6% and 68.8%
(using Phoenix criteria) for low-, intermediate- and
high-risk patients with a mean follow up of 22.2 months.
However, 3 patients of our cohort also had histological
proven recurrence without biochemical recurrence.
Previous studies by Ganzer et al. showed, that negative biopsy
rates correlate with postoperative PSA nadir. Ganzer et al.
described negative biopsy rates of 91.6% for patients with
PSA nadir ≤ 0.2 ng/ml. Thus, 8.4% of patients had
remaining prostate cancer tissue in control biopsies after
3–6 months  with a PSA value < 0.2 ng/ml.
In our cohort, side effects were limited in severity. Main
complications were urinary tract infections and
infravesical obstruction. While infections were mainly managed
successfully by antibiotic treatment, 25% of patients
needed further surgical treatment in form of transurethral
resection of bladder neck strictures. These complications
and rates were also described in other publications as the
most frequent re-interventions [18–20]. More severe
complications like fistulas did not occur in our cohort.
Regarding postoperative micturition and continence, IPSS
and uroflowmetry data did not change after HIFU
treatment. Previous studies could show, that combining TURP
and HIFU is mandatory to reduce postoperative voiding
dysfunction . However, even previous TURP cannot
reduce infravesical obstruction completely. During
followup, 35.1% of patients needed further treatment for
infravesical obstruction after HIFU treatment. Previous studies
confirm, that bladder neck obstruction or urethral
strictures are the most common side effects of HIFU
treatment [5, 18]. Crouzet et al. described up to 16% bladder
neck obstruction in their group, when TUR-P and HIFU
were combined in one session. To reduce these side
effects, an interval of up to 6 weeks between TUR-P and
HIFU has been proposed  with reduction of
infravesical obstruction to 11%, as described by Crouzet et al. .
Compared to our cohort, median pre-HIFU prostate
volume was smaller in the cohort described by Crouzet et al.
(22–24.5 ml) compared to our cohort (38.5 ml), which
could explain the higher bladder neck obstruction rates in
the present study due to a selection bias.
Evaluation of erectile function in our group
revealed, that postoperative erectile function depends
Global health status/QoL (QL2)
Physical functioning (PF2)
Role functioning (RF2)
Emotional functioning (EF)
Cognitive functioning (CF)
Social functioning (SF)
Nausea and vomiting (NV)
Financial difficulties (FI)
Sexual functioning (PRSFU)(n = 71)
Urinary symptoms (PRURI)
Urinary bother (PRAID)
Bowel symptoms (PRBOW)
ADT – treatments symptoms (PRHTR)
Quality - of - life; IPSS
on nervesparing procedure. Most studies do not report of
nervesparing as this means sparing a few millimeters of
prostatic tissue and therefore increasing the risk for
biochemical recurrence . As expected, the PSA nadir
ranges were higher (up to 6.5 ng/ml), most likely because
of nervesparing procedure, that has been done in 35.9% of
patients. Warmuth et al.  reviewed 20 studies with a
total of 3018 patients undergoing whole gland ablation and
reported of erectile dysfunction rates ranging from 20–
39%. Crouzet et al.  recently reported their results of
1002 patients and described preservation of erectile
function in 42.3% patients (<70 years: 55.6%; >70 years: 25.6%).
None of these trials took nervesparing procedure into
account. In our cohort, erectile function could be preserved
in only 15% in patients undergoing whole gland ablation.
These patients tended to be of advanced age (mean age in
non-nervesparing group was 74.4 years), that is known to
be associated with impaired baseline potency status 
and therefore these patients normally do not wish
nervesparing procedure. In contrast, both sided nervesparing
HIFU could preserve erectile function in up to 66% of our
patients (median age in this group was 69.7 years).
Patients undergoing HIFU ablation instead of standard
treatment commonly expect less side effects and better
preservation of quality of life. As quality of life
represents a multidimensional construct that includes
physical, social, psychological and functional domains, its
assessment needs complex and standardized
questionnaires. Shoji et al. examined the changes in quality of life
for patients at a mean age 68 years undergoing HIFU by
using the japanese versions of the FACT-G and FACT-P
questionnaires (functional assessment of cancer therapy
– general and prostate cancer module) . The authors
reported, that general quality of life improves after HIFU
therapy while the values for FACT-P questionnaire did
not change. However, patients undergoing HIFU may be
biased as they actively rejected standard therapy for a
new, minimal invasive therapy option. We evaluated
quality of life after HIFU therapy using the standardized
QLQ-C30 and QLQ-PR25 questionnaire. Mean global
health score after HIFU treatment was 69.4% for all
patients, 66.4% for patients ≤70 years and 70.9% for
patients >70 years. Schwarz et al. evaluated QLQ-C30 data
for the general german population  and described
global health scores of 65.6% and 61.5% for patients ≤70
and >70 years, respectively. When compared to the
general german population, patients after HIFU treatment
show better quality of life with respect to global health
scores. Drummond et al. evaluated quality of life after
standard therapy in more than 6000 patients within the
PiCTure study (prostate cancer treatment, your
experience) . They described global health scores ranging
from 73.4% for radical prostatectomy and 69.4% for
external beam radiation therapy. With respect to the
younger patient collective in the PiCTure study, global
health score after HIFU treatment in our collective
ranged within the scores after standard treatment
options described by Drummond et al. Comparing the
results of QLQ-PR25 items revealed more urinary
symptoms (28.3% for HIFU vs. 19.8% for standard
treatment ) and more urinary bother (38.6% for HIFU vs.
15.6% for standard treatment ) and less sexual activity
(56.9% for HIFU vs. 67.8% for standard treatment ).
Limitations of the study include short followup. Results
predicting oncological safety need longer followup
periods, that should be considered in further studies.
Another limitation is the missing, preoperative assessment
for quality of life to compare changes for this parameter.
In conclusion, HIFU treatment for localized prostate
cancer shows acceptable oncological safety in limited
follow up. However, local recurrence is not always
indicated by biochemical recurrence. Compared to literature,
the quality of life after HIFU showed better results
compared to general population of equivalent age. Patients’
satisfaction ranges within those of standard treatment
options. Further studies are needed to compare changes
in quality of life before and after HIFU therapy. In
addition, nearly 25% of patients needed further
treatment for bladder neck obstruction. HIFU seems a safe
valuable treatment alternative for patients not suitable
for standard treatment.
EORTC: European Organisation for Research and Treatment of cancer;
HIFU: High intensified focused ultrasound; IIEF-5: International index for
erectile function; IPSS: International prostate symptom score; QLQ: Quality of
life questionnaire; TURP: Transurethral resection of the prostate
Availability of data and materials
The datasets generated and/or analysed during the current study are not
publicly available due to ethical restrictions but are available from the
corresponding author on reasonable request.
GH, IVP and MD carried out data acquisition and data analysis. GH
participated in design of the study and drafted the manuscript. JND, DT and
BH helped in designing the study and revised the manuscript critically. SP,
DT and MH made substantial contribution to conception and design,
analysis of data, critically revising the manuscript and final approval. DT and
SP contributed equally. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Ethics approval and consent to participate
The study protocol was approved by the ethics committee of the University
of Heidelberg (S-182/2012). All patients gave written informed consent.
Nervesparing was only done in patients, explicitly demanding for this with
full awareness of higher risk of tumor recurrence. This was also documented
in the informed consent.
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