Introduction
Prostate cancer (PCa) is the most common malignancy
in men and the 2nd most common cause of cancer-related
deaths.[] As a result of increased prostate-specific-
antigen (PSA) screening, early stage PCa cases are
increasing. With more experience with low risk PCa, a conservative approach has emerged because of the
worries about overdiagnosis, overtreatment and treatment-
related toxicities.[] Active surveillance (AS)/
watchful waiting (WW) have become to be used more
frequently in the management of PCa. In a recent study
including data of 50302 low-risk PCa patients from
Surveillance, Epidemiology, and End Results database, it was reported that, from 2010 to 2015, AS/WW rates
have increased from 11.2 to 37.3%, 14.1 to 45.8% and
17.6 to 46.4% in the low, middle and high socioeconomic
status groups, respectively.[]
Although there are some controversies and differences
about the implementation of AS between institutions,
it"s mainly recommended for selected very low/
low risk and low-volume favorable intermediate risk
(Gleason 3+4) PCa patients. In the literature, AS has
been confirmed by various studies as a safe, appealing
and effective treatment strategy.[,] Long-term outcomes
of the prostate cancer intervention versus observation
(PIVOT) trial showed no survival advantage
with radical prostatectomy (RP) over observation in
low risk PCa patients.[] Consistent with PIVOT trial,
the prostate testing for cancer and treatment (ProtecT)
trial showed no survival benefit of RP or radiotherapy
(RT) as compared to active monitoring, for patients
with localized disease.[] In contrast to above-mentioned
2 major studies, only Scandinavian prostate
cancer group-4 (SPCG-4) trial showed survival benefit
with RP over WW.[] The benefit was largest in patients
<65 years of age and in those with intermediaterisk
PCa. But, it should be kept in mind that this study
was performed in the pre-PSA era. Small differences
in inclusion and follow-up criteria of studies may also
explain this discrepancy.
Considering all these data, it is reasonable to use
AS in selected cases to avoid/delay treatments and their
side effects. AS has been reported to be able to reduce
overtreatment and treatment costs in group of patients
with low-risk PCa.[] Therefore, awareness and attitudes
of PCa specialists towards AS are quite important
for the adoption of AS in the management of PCa. The
literature includes different results in a limited number
of studies evaluating physicians" attitudes towards AS.
In a national survey in which respondents were radiation
oncologists (ROs) and urologists (UROs), physicians"
perceptions of possible barriers towards AS for
low-risk PCa were analyzed. Prejudice of low interest of
patients in AS, worries about repeated prostate biopsy
necessity, biased treatment suggestions of physicians
in favor of their own expertise were reported as key
barriers to AS.[] Another recent survey study was
conducted with 52 respondents who are ROs, medical
oncologists (MOs) or UROs. Fear of patient non-compliance
and lack of awareness were the main impediments
for the implementation of AS.[]
In present study, we performed a questionnaire in
Turkey to evaluate the perspectives of ROs, MOs and
UROs towards AS. To the best of our knowledge, this is the largest study evaluating the attitudes of ROs, MOs
and UROs towards AS in the management of PCa.
Methods
The study was conducted as a cross-sectional questionnaire
study, in order to assess the attitudes of ROs, MOs
and UROs towards AS in the management of PCa. Institutional
Ethics Committee approved the study protocol.
All procedures performed in studies involving
human participants were in accordance with the ethical
standards of the institutional and/or national research
committee and with the 1964 Helsinki declaration and
its later amendments or comparable ethical standards.
Informed consent was obtained from all individual
participants included in the study.
A structured questionnaire with a total of 24
questions was designed electronically. It contained
dichotomous and multiple-choice questions evaluating
the physicians" sociodemographic characteristics
(questions 1-7), their current primary treatment
preferences for low-risk PCa (questions 14-17) and
their attitudes towards AS (the remaining questions).
The whole questionnaire was shown in Annex File 1.
Between September-October 2019, 598 physicians
were invited to study by e-mails and the responses
were collected. The invitation e-mails were sent 3
times in the 2 months of data collection period to enable
more feedbacks.
Descriptive analyses were done using frequencies
for the sociodemographic variables. In order to assess
for differences in physician characteristics and questionnaire
answers, bivariate analyses were conducted
using Pearson chi-square test. To analyze the factors
associated with recommending AS, the academic
ranking was grouped as academic staff (professor,
assoc./asst. professor) and others. The primary place
of work was grouped into reference hospital (university/
education and research hospital) and others. The
parameters associated with more recommendations
of AS (with p value<0.2) were used for multivariate
analysis. Multivariable logistic regression models
were carried out to identify relevant factors of participants,
which were associated with different attitudes of
physicians about AS.
The Statistical Package for the Social Sciences
(SPSS) version 21.0 (SPSS Inc., Chicago, Illinois, USA)
was used for statistical analysis and a p-value of less
than 0.05 was considered statistically significant.
Results
A total of 244 participants (response rate: 40.8%) completed
the questionnaire. The baseline characteristics
of the participants are summarized in Table 1. Most
of the participants were male (182, 74.6%) and nearly
half of them were between 30 and50 years of age (129,
52.9%). There were 129 UROs (52.9%), 76 ROs (31.1%)
and 39 MOs (16%) in the study population. The most
common primary place of work was a university/education
and research hospital (160, 65.6%). While half
of them were specialists (122, 50.0%), 52.9% of them
had been caring cancer patients for more than 10 years.
One-fourth of the physicians (25.6%) stated that they
had never had a multidisciplinary uro-oncology board
during their medical career. The participants declared
that the probability of overtreatment (61.1%) was the
most challenging problem in the management of PCa.
Among the participants, the asst.professor/professors
(72.0% vs 54.3%, p=0.04) and UROs (66.7% vs 54.8%,
p=0.03) had more concerns about overtreatment. In
addition, 44.7%, 27.9% and 20.1% of them thought
that there were still problems in treatment, screening
and diagnosis of PCa, respectively. When compared
to UROs (41, 31.8%), more MOs (27, 69.2%) and ROs (41, 53.9%) thought that there were problems in terms
of treatment modalities (p<0.001). Additionally, 35.9%
of the MOs worried about screening in PCa (26.3% of
ROs and 26.4% of UROs, p<0.001).
Table 1: The baseline characteristics of the participants
Almost every four out of 5 physicians (79.9%) were
suggesting AS to PCa patients in their daily practice,
while 76.6% of them thought that they had enough
knowledge about inclusion criterias of AS for PCa. A
great majority (91%) of the physicians declared that
AS could be beneficial for selected patients. However,
47 physicians (19.3%) worried about monitoring patients
with AS and 22 physicians (9.0%) thought that
they had inadequate experience to monitor a patient
with AS. The analysis of the important factors while
considering AS showed that prostate cancer risk group
(85.7%) was the most commonly considered criteria,
followed by patient's request/compliance (84.8%), life
expectancy (76.2%) and sexual activity status of the patient
(34.8%). The factors considered by different specialties
were summarized in Figure 1.
Fig 1: The results of the factors while considering active
surveillance in terms of different specialties.
UROs: Urologists, ROs: Radiation oncologists, MOs: Medical
oncologists.
The AS was recommended by 86.8% of UROs,
77.6% of ROs and 61.55% of MOs (p=0.002) (Table 2).
More UROs thought that they had enough knowledge
about AS (82.9% vs 69.6, p=0.01). The ones working in
university/education and research hospital had more
tendency to recommend AS (85.0% vs 70.2%, p=0.006).
In addition, academic staff recommended AS more often
when compared to others (88.2% vs 74.8, p=0.008).
The physicians who had an uro-oncology board experience
in their career (86.7%) recommended AS more
when compared to those who didn"t (72.4%) have an
uro-oncology board experience (p=0.004). In multivariate
analysis, practicing as ROs (OR: 2.7, CI95%
1.09-6.7, p=0.031) or UROs (OR: 0.03, CI 95% 3.3- 24.6, p<0.001), working in a reference hospital (OR:
3.03, CI 95% 1.3-6.7, p=0.006) and having an uro-oncology
board experience (OR: 2.2, CI 95% 1.07-4.8, p=
0.031) were associated with more recommendations
for AS (Table 3).
Table 2: The factors effecting recommendations for active
surveillance
Table 3: Multivariate analysis of factors associated with recommendation for active surveillance
Majority of the physicians (88.9%) had concerns
about AS. The most common concern was the noncompliance
of patients (79.1%), followed by the risk of
losing a curative treatment opportunity (34.8%). Additionally,
25.8% and 18.9% of the physicians had concerns
of local progression risk and lymphatic/systemic
metastasis risk, respectively. A minority of participants
(19, 7.8%) had concerns about inadequacy of data in
literature. The concerns of different specialties were
summarized in Figure 2.
Fig 2: The concerns of different specialties about active
surveillance.
UROs: Urologists, ROs: Radiation oncologists, MOs: Medical
oncologists.
As a primary treatment of PCa patients with life expectancy
of ?10 years, 54.1% and 2% of the physicians
recommended AS for very low/low risk and favorable
intermediate risk groups, respectively. For favorable
intermediate risk patients, RP (60.2%) was the most
commonly recommended primary treatment option,
followed by RT (36.9%). On the other hand, as a primary
treatment of PCa patients with life expectancy of
<10 years, 52.5% and 10.2% of the physicians recommended
AS for very low/low risk and favorable intermediate
risk groups, respectively. The most commonly
recommended primary treatment option was RT
(70.9%) for favorable-intermediate risk patients with
life expectancy of <10 years.
For localized disease, 75% of the physicians preferred
to use multiparametric prostate magnetic resonance
imaging (MPMRI) to make a decision for AS. A
great majority of the physicians (95.1%) used PSA test
for AS protocol. Others were MPMRI (69.7%), prostate
biopsy (65.6%) and digital rectal examination (65.2%),
respectively.
Unless clinically indicated, most of the physicians
(69.7%) suggested assessing AS patients in every 3
months and similarly, 66.8% of them suggested an evaluation
with PSA test in every 3 months. There was no
consensus for the evaluation interval with digital rectal
examination (DRE). While 38.1% of the physicians
suggested an evaluation with DRE in every 3 months,
35.7% of them suggested DRE in every 6 months. 126
physicians (51.6%) suggested prostate biopsy annually,
and 50.8% of the physicians used MPMRI annually.
Discussion
Active surveillance has become an increasingly used
treatment strategy for low risk PCa. Our study showed
that a great majority of PCa physicians (ROs, MOs and
UROs) in Turkey think that AS could be beneficial for
selected PCa patients and, AS was being suggested by
every 4 out of 5 PCa physicians.
A recent study with a small number of participants
(52 physicians in total, including 5 ROs, 8 MOs and
39 UROs) reported that AS was more commonly suggested
by UROs, physicians with >15 years in practice
and physicians working in university hospitals.
[] Consistent with this study, our study showed that
physicians working in a reference hospital were more
likely to suggest AS. Additionally, UROs seemed to be
a pillar support for the implementation of AS in PCa
treatment and ROs were recommending AS more than
MOs. Unlike this study, longer-term practice in oncology
was not related to more recommendation for AS.
Moreover, being a member of the academic staff and
having an uro-oncology board in medical institution
were associated with more AS suggestion of physicians.
Briefly, our results demonstrated that being UROs or
ROs rather than MOs and working in more academic
or multidisciplinary conditions may lead PCa physicians
to offer AS more.
In another study, age and comorbidities were seen
as the only patient characteristics which might influence
all physicians on their treatment recommendation
of AS. Patient's willingness and ability to follow
an AS protocol, patient's treatment preferences and life
expectancy were major factors influencing physicians"
treatment recommendation of AS.[] In our study,
prostate cancer risk group and patient's request/compliance
were the main considerations of physicians for
the implementation of AS.
Although physicians" AS suggestion rates were up
to 80% in our study, 88.9% of the physicians had at least
one concern about AS, most commonly "non-compliance of patients". Patient non-compliance may be associated
with many factors. In their national study, Kim
et al.[] reported a substantive rate of ROs and UROs
perceive that several newly diagnosed low-risk PCa
patients desire some form of primary treatment and
not interested in AS. Additionally, the Prostate Cancer
Research International Active Surveillance (PRIAS)
study demonstrated the reluctance of patients to undergo
yearly biopsies, which may be also interpreted
as patient non-compliance.[] As might be expected,
newly diagnosed low-risk PCa patients may probably
have concerns about their treatment options and
this situation may influence patient compliance. If AS
is to be selected, it's clear that patients should be informed
about the protocol in detail. In a longitudinal
cohort study, it was reported that men preferring AS
had greater knowledge and awareness of having lowrisk
PCa, but also were less certain about their treatment
preference, had a greater anxiety and preferred a
shared treatment decision.[] Compatibly, good communication
and trustful relationship between patients
and physicians were indicated as major factors for lowrisk
PCa patients to enroll to AS protocol.[,]
In case scenarios; when asked for a primary treatment
recommendation for very low/low risk PCa patients
with life expectancy of ≥10 years, only 54.1% of
the physicians recommended AS. This result was nearly
20% and 50% in Kim et al.'s [] and El Sebaaly et al.'s
[] studies, respectively. Biased treatment suggestions
of physicians in favor of their own expertises and influences
of physicians" concerns on treatment decisions
may explain these low rates.
When asked for a primary treatment recommendation
for very low/low risk PCa patients with life
expectancy of <10 years, 52.5% of the physicians recommended AS. This result indirectly revealed that
observation is not a generally accepted management
strategy in this group of patients for PCa physicians
who participated in this study. It may also be interpreted
as awareness should be raised among physicians
to distinguish AS from observation. Regardless of life
expectancy of the patients, physicians didn't recommend
AS for patients with favorable intermediate risk.
This study demonstrated that there was no majority
consensus for a certain AS protocol among physicians.
Although a great majority of the physicians preferred
to use PSA test for AS protocol, there were differences
about the optimal time interval for an evaluation with
PSA test. To make a decision for AS, MPMRI were
recommended by 75% of the participants. During follow-
ups for AS, physicians" suggested rates of use of
DRE, prostate biopsy and MPMRI were less than 70%.
In addition, physicians couldn"t reach a consensus on
the optimal time interval for an evaluation with DRE,
prostate biopsy and MPMRI. These results were compatible
with the findings of Ganz et al.[] in which
no consensus was reported on patient selection and
follow-up protocols for AS. Significant heterogeneities
in AS protocols were also reported in several different
studies.[-] Therefore, it is important to establish a
standart AS protocol to make the outcomes of the obtained
data more valid and accurate.
Limitations and Strength of the Study
The limitations of our study are as follows. 1) Our questionnaire
is not validated as there were no validated
questionnaires on this topic. 2) Because this is a questionnaire
study, we were only able to analyze limited
data. There may be more questions to be addressed. 3)
This study evaluated only perspectives of ROs, MOs
and UROs towards AS and also did not assess the perspectives
of the patients. 4) The number of medical
oncologists was relatively lower than other physicians.
The strength of our study is being the largest study evaluating
the attitudes of ROs, MOs and UROs towards
AS in the management of PCa. Above-mentioned (or
even may be more) limitations were also present in
other similar studies.
Conclusion
Being UROs or ROs rather than MOs and working in
more academic or multidisciplinary conditions may
lead PCa physicians to offer AS more. Biased treatment
suggestions of physicians in favor of their own expertise
and influences of physicians" concerns on treatment decisions may decrease the AS suggestion rates. It's critical
to establish a certain AS protocol which could make
obtained data outcomes more valid and accurate. It is
also reasonable to raise awareness among physicians to
distinguish AS from observation. In general, physicians
don't recommend AS for PCa patients with favorable intermediate
risk.
Acknowledgement: We would like to thank all the prostate
cancer specialists who took the time to voluntarily complete
our questionnaire.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declare that they have no
conflict of interest.
Ethics Committee Approval: This study was approved by
the Muğla Sıtkı Koçman University Medical Faculty Ethics
Committee (no. 147, date: 27.08.2019).
Financial Support: None declared.
Authorship contributions: Concept - G.T., A.A., İ.A., Ö.T.,
H.Ş.; Design - G.T., A.A., İ.A.; Supervision - G.T., A.A., İ.A.,
Ö.T., H.Ş.; Funding - G.T., A.A., İ.A., Ö.T., H.Ş.; Materials -
G.T., A.A., İ.A., Ö.T., H.Ş.; Data collection and/or processing
- G.T., A.A., İ.A., Ö.T., H.Ş.; Data analysis and/or interpretation
- G.T., A.A.; Literature search - G.T., A.A.; Writing -
G.T., A.A.; Critical review - G.T., A.A., İ.A., Ö.T., H.Ş.
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