Original research

Diagnosis, referral, and primary treatment decisions in newly

diagnosed prostate cancer patients in a multidisciplinary diagnostic

assessment program

David Guy, MD; Gabriella Ghanem, MD; Andrew Loblaw, MD; Roger Buckley, MD; Beverly Persaud, MD;

1,2,3

1,3

Patrick Cheung, MD; Hans Chung, MD; Cyril Danjoux, MD; Gerard Morton, MD; Jeff Noakes, MD;

Les Spevack, MD; David Hajek, MD; Stanley Flax, MD

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto,

Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Urology, North York General Hospital, Toronto, ON, Canada

Cite as: Can Urol Assoc J 2016;10(3-4):120-5. http://dx.doi.org/10.5489/cuaj.3510

Introduction

In 2015, an estimated 24 000 men in Canada will be diag-

Abstract

nosed with prostate cancer (PCa) and will need to decide

Introduction: We aimed to report on data from the multidisciplin-

ary diagnostic assessment program (DAP) at the Gale and Graham

Wright Prostate Centre (GGWPC) at North York General Hospital

between a variety of management options. For many, this

can be distressing and lead to post-treatment regret and worse

quality of life. Most commonly, a patient diagnosed with

PCa will meet with their urologist to learn about manage-

ment options. Sometimes a referral for consultation with a

radiation oncologist is made. The literature has reported that

each specialist is more likely to recommend treatment that

(

NYGH). We assessed referral, diagnosis, and treatment decisions

for newly diagnosed prostate cancer (PCa) patients as seen over

time, risk stratiﬁcation, and clinic type to establish a deeper under-

standing of current decision-making trends.

Methods: From June 2007 to April 2012, 1277 patients who were

diagnosed with PCa at the GGWPC were included in this study.

Data was collected and reviewed retrospectively using electronic

patient records.

they provide. In anticipation for an increase in the number

of PCa diagnoses in the coming years, an understanding

of the decision-making process is exceedingly important.

In 2007, the Gale and Graham Wright Prostate Centre

(GGWPC), in collaboration with the Odette Cancer Centre

(OCC), was established at North York General Hospital

Results: 1031 of 1260 patients (81.8%) were seen in a multidisci-

plinary clinic (MDC). Over time, a decrease in low-risk (LR) diagno-

ses and an increase intermediate-risk (IR) diagnoses was observed

(p<0.0001). With respect to overall treatment decisions 474 (37.1%)

(

NYGH). As a diagnostic assessment program (DAP), the

of patients received primary radiotherapy, 340 (26.6%) received

surgical therapy, and 426 (33.4%) had conservative management;

goal is to improve timely access and the quality of care

provided to men with PCa. Our group has already shown

that wait times from suspicion to radiation treatment is, on

average, two months shorter in the GGWPC vs. standard

7% of patients who were candidates for active surveillance were

managed this way. No signiﬁcant treatment trends were observed

over time (p=0.8440). Signiﬁcantly, different management deci-

sions were made in those who attended the MDC compared to

those who only saw a urologist (p<0.0001).

Conclusions: In our DAP, the vast majority of patients presented

with screen-detected disease, but there was a gradual shift from

low- to intermediate-risk disease over time. Timely multidisciplin-

ary consultation was achievable in over 80% of patients and was

associated with different management decisions. We recommend

that all patients at risk for prostate cancer be worked up in a multi-

disciplinary DAP.

community practice (183 vs. 138 days, p=0.046).

Patients are referred from general practitioners or com-

munity urologists if they have an elevated prostate-speciﬁc

antigen (PSA) in the absence of instrumentation, abnormal

digital rectal examination (DRE) or abnormal imaging sug-

gestive of PCa. Patients are seen by one of ﬁve urologists

and their prostate cancer risk assessed within two weeks

of referral. If a biopsy is warranted, this is also done in the

clinic within two weeks. Results of the biopsy are given

within two weeks of biopsy and if the patient is diagnosed

with cancer, the patient seen by both urology and radia-

tion oncology within a week (staging tests are arranged, if

appropriate). Throughout the diagnostic journey, the patient

CUAJ • March-April 2016 • Volume 10, Issues 3-4

2016 Canadian Urological Association

Dꢀꢁꢂꢃoꢄꢀꢄ ꢁꢃd tꢅꢆꢁtmꢆꢃt tꢅꢆꢃdꢄ ꢁt ꢁ muꢇtꢀdꢀꢄꢈꢀpꢇꢀꢃꢁꢅy pꢅoꢄtꢁtꢆ DaP

is supported by our expert nurse, clinical coordinator, and

Prostate Cancer Canada Network volunteers.

to April 26, 2012), data for the number of diagnosis was

prorated for a 12-month year. Treatment decisions among

patients who attended a multidisciplinary clinic (MDC) were

compared with those in a non-MDC setting using a Chi-

square test. A separate analysis was done for patients decid-

ing between surgical therapy (RP) and radiation therapy (RT)

treatments alone, as opposed to those also considering con-

servative management (CM).

The purpose of this study is to examine data from GGWPC

regarding referral, diagnosis, and treatment decisions for

newly diagnosed PCa patients. This data was examined over

time, risk stratiﬁcation, and clinic type to establish a deeper

understanding of current decision-making trends.

The LIR and HIR groups were combined into one inter-

Methods

mediate risk (IR) group and generalized linear model was

used to test for a signiﬁcant trend over time between IR and

LR groups. Generalized linear model (GENMOD) procedure

was applied for this analysis using Statistical Analysis Software

(SAS version 9.4 for Windows). The outcome of the model

was percent of patients per year; the independent variables

were year (2007‒2012), risk group (IR vs. LR), and interaction

between year and risk group (year × risk). GENMOD was also

used to test for a signiﬁcant difference over time between the

proportion of patients choosing between CM, RP, or RT. The

outcome of the model was percent of patients per year; the

independent variables were year (2007‒2012), treatment (RP,

RT, or CM), and interaction between year and treatment (year

× treatment). For the purposes of these analyses, we deﬁned

CM as no therapy, active surveillance, or primary androgen-

deprivation therapy (ADT).

Patients

From June 2007 to April 2012 at the GGWPC, there were

2 856 patient encounters, 3231 prostate biopsies per -

formed, and 1358 patients newly diagnosed (an additional

3 patients were re-biopsied on an active surveillance proto-

col). Eighty-one patients were excluded from these analy-

ses due to: lack of followup information (n=75); recurrent

disease (n=4); diagnosed before observation window (n=2).

This left 1277 patients in the study.

Data collection

Data was collected and reviewed retrospectively using elec-

tronic patient records. Information obtained included age at

diagnosis, biopsy date, reason for referral, prognostic factors at

diagnosis (pre-biopsy PSA level, TNM stage, Gleason Score (GS),

and percent core involvement), and initial treatment decision.

PCa risk was divided into ﬁve strata based on the Prostate

Results

From June 2007 to April 2012, 1277 patients were diagnosed

with PCa at GGWPC in NYGH. On average, 258 patients

were diagnosed per year (range 212‒277). The median age

of diagnosed patients was 67.2 years old (range 41–93) and

was stable over time.

Cancer Risk Stratiﬁcation (ProCaRS) database. PROCARS

is similar to other risk classiﬁcation schemes except that

it further subdivides the intermediate- and high-risk groups

into low and high tiers, respectively. Classiﬁcations are: low-

risk disease (LR) (clinical stage ≤T2b, GS≤6 and PSA≤10 ng/

mL); low-intermediate-risk disease (LIR) (PSA≤10 ng/mL and

Among newly diagnosed patients, almost all were referred

due to an abnormal PSA. Eight hundred twenty-nine men

(64.9%) were referred for an elevated PSA alone, 394

(30.9%) for an abnormal PSA and DRE, 13 (1.0%) for an

abnormal DRE, and one (0.1%) for benign prostatic hyper-

trophy (BPH). Suspicious pathological ﬁndings were the rea-

son for referral for less than 1% of diagnosed men (typical

small acinar proliferation [ASAP] in nine patients [0.7%];

high-grade prostatic intraepithelial neoplasia [HGPIN] in

one patient [0.1%]). Data with respect to reason for biopsy

was unavailable for 30 men (2.3%). Over time, the propor-

tion of patients with missing data and those referred for an

elevated PSA alone decreased slightly (Fig. 1).

[GS=7 or clinical stage=T2c]), high-intermediate-risk disease

(

clinical stage=T2c); high-risk disease (HR) (PSA>20 ng/mL or

clinical stage=T3-T4 or GS=8-10); and very-high-risk disease

HIR) (GS=7 and one or both of PSA 10‒20 ng/mL and/or

(

PSA>30 ng/mL or having high-volume disease, deﬁned as

87.5% biopsy core involvement). For patients who were

staged, the results of the bone scans and computed tomog-

raphy (CT) scans for patients were reviewed and men with

metastatic disease were documented.

Analyses

Management decisions are summarized in Table 1. Of the

277 men included in the study, data on management was

The initial treatment choice following diagnosis was exam-

ined at each risk stratum. Reasons for referral, quantity of

diagnoses, and risk status were examined on an annual basis

from June 2007 to April 2012. For time periods less than

a year (June 13, 2007 to May 31, 2008 and June 1, 2011

unavailable for 32 patients (2.5%), leaving 1245 patients. PR

was given to 474 (38.1%) patients, of which 203 (42.8%)

received primary external beam radiation therapy (EBRT), 107

(22.6%) received brachytherapy (BT) alone, and 48 (10.1%)

received EBRT with a BT boost. Additionally, 340 (27.3%)

CUAJ • March-April 2016 • Volume 10, Issues 3-4

121

guy ꢆt ꢁꢇ.

PSA and DRE

PSA

None

DRE

ASAP

Jun/07-Jun/08 Jun/08-Jun/09 Jun/09-Jun/10 Jun/10-Jun/11 Jun/11-Jun/12

Fig. 1. Annual reason for referral among diagnosed patients over time. ASAP: small acinar proliferation; DRE: digital rectal examination; PIN: prostatic intraepithelial

neoplasia; PSA: prostate-speciﬁc antigen.

received RP, while 426 (34.2%) were managed conservative-

ly. Of the 426 conservatively managed patients, 353 (82.9%)

were managed with active surveillance and 73 (17.1%) were

managed with primary ADT. Less than 1% of patients chose

high-intensity focused ultrasound (HIFU) or chemotherapy. No

signiﬁcant trend (p=0.8440) was found among proportion of

patients choosing active surveillance, RP, and RT over time.

Of the 1277 men with PCa, 41 (3.2%) had metastatic

disease. T category, GS, and PSA values were available for

1110 (89.9%) of the patients diagnosed with localized dis-

ease. Three-hundred seventy-six (33.9%), 373 (33.6%), 137

(12.3%), 92 (8.3%), and 132 men (11.9%) had low-, low-

intermediate-, high-intermediate-, high- and very-high-risk

PCa, respectively. This information is summarized in Table

2 and also divided by treatment decision.

Risk status at time of diagnosis is summarized annu -

ally in Fig. 2. The graph shows that over time, IR disease

diagnoses increased and LR disease diagnoses decreased.

Signiﬁcant time trends (p=0.0203) and a highly signiﬁcant

difference (p<0.0001) between the IR and LR groups was

found. Additionally, the interaction term between year

and risk group was highly signiﬁcant, indicating LR and IR

have completely different time trends. The HR disease rates

remained stable.

Table 1. Primary treatment decision after diagnosis among

1245 patients with management data (32 patients had no

data available)

approach

of type of

% of total

Primary treatment approach

Radiotherapy

474

203

38.1%

16.3%

6.5%

Of the 1277 patients, there were no data regarding attend-

ance in a MDC for 17 men (1.3%), leaving 1260 patients;

EBRT

42.8%

17.1%

7.4%

EBRT + ADT

024 (81.3%) were seen in a MDC. The differences in treat-

SABR

2.8%

ment decisions in a MDC compared to a non-MDC are

presented in Fig. 3. Of the 1024 patients seen in a MDC,

the majority opted for RT, followed by CM, and lastly RP.

Of the 236 patients not seen in a MDC, the majority opted

for CM, followed by RP, then RT. This difference was highly

signiﬁcant (p<0.0001). Additionally, a highly signiﬁcant dif-

ference (p<0.0001) was found in the proportion of patients

choosing either RT or RP with more patients opting for RT

in a MDC setting.

EBRT + brachytherapy

Brachytherapy alone

Conservative management

10.1%

22.6%

3.9%

107

426

8.6%

34.2%

Active surveillance/watchful

waiting

353

82.9%

17.1%

28.4%

Primary ADT

Radical prostatectomy

Open

340

5.9%

27.3%

2.9%

0.0%

0.3%

24.1%

0.4%

0.2%

10.6%

0.0%

Laparoscopic

Robotic

1.2%

Discussion

Unknown

300

88.2%

Other

This study reports the diagnostic and treatment results over

time from a large Canadian DAP for prostate cancer from

HIFU

60.0%

40.0%

Chemotherapy

ADT: androgen-deprivation therapy; EBRT: external beam radiotherapy; HIFU: high-

intensity focused ultrasound; SABR: stereotactic ablative radiotherapy.

Canadian centres.

007‒2012. We are not aware of any similar data from other

CUAJ • March-April 2016 • Volume 10, Issues 3-4

Dꢀꢁꢂꢃoꢄꢀꢄ ꢁꢃd tꢅꢆꢁtmꢆꢃt tꢅꢆꢃdꢄ ꢁt ꢁ muꢇtꢀdꢀꢄꢈꢀpꢇꢀꢃꢁꢅy pꢅoꢄtꢁtꢆ DaP

Table 2. Primary treatment by risk category

Risk category

Initial treatment

LIR

HIR

VHR

222

59.0

13.8

5.3

0.2

AS/WW

15.5

8.8

25.5

8.3

2.1

0.3

8.8

6.6

35.8

2.9

8.8

6.5

1.1

15.2

2.2

25.0

5.3

3.8

12.1

3.0

20.5

EBRT

EBRT & BT

EBRT & ADT

HIFU

0.5

Primary ADT

SABR

1.5

2.9

31.4

1.5

100

10.9

5.4

30.4

3.3

100

24.2

6.8

18.2

6.1

100

2.1

1.6

36.5

1.3

100

136

Unknown

2.1

Total

376

100

373

137

132

ADT: androgen-deprivation therapy; AS: active surveillance; BT: brachytherapy; EBRT: external beam radiotherapy; HIFU: high-intensity focused ultrasound; HIR: high-intermediate-risk;

HR: high-risk; LIR: low-intermediate-risk; LR: low-risk; RP: radical prostatectomy; SABR: stereotactic ablative radiotherapy; VHR: very-high-risk; WW: watchful waiting.

Between 2007 and 2012, the proportion of patients diag-

nosed with LR disease decreased, while the proportion of

patients with IR disease increased (p<0.0001). This was like-

ly due to grade migration after the International Society of

Urologic Pathologists’ 2005 recommendations where poorly

formed glands and any cribiform pattern (Gleason pattern

lance. While both the National Institute for Heath and Care

Excellence (NICE) and Cancer Care Ontario (CCO) active

surveillance guidelines allow the use of active surveillance

16,17

for selected IR patients,

further data is calling this practice

into question. Data from the Sunnybrook cohort presented at

the 2015 Genitourinary Cancers Symposium reported that IR

patients at baseline managed with active surveillance have

an increased risk of PCa death (hazard ratio 3.74, p=0.01)

b and 3c) were reassigned pattern 4.

We were encouraged by the high proportional use of

active surveillance in LR patients (59%), which seems to be

compared to patients with LR disease.

12,13

higher than other jurisdictions in Canada or the U.S.

may reꢀect a comfort level stemming from Sunnybrook’s and

This

Interestingly, there were signiﬁcantly different manage-

ment choices made by the approximately 20% of patients

who did not attend a MDC consult. Patients not attending

were more likely to choose active surveillance (64% vs.

14,15

others’ seminal work in the region.

LIR and 9% of HIR patients were managed by active surveil-

We noted that 16% of

VHR

HIR

LIR

Jun/07-Jun/08

Jun/08-Jun/09

Jun/09-Jun/10

Jun/10-Jun/11

Jun/11-Jun/12

Fig. 2. Annual risk category of diagnosed patients. HIR: high-intermediate-risk; HR: high-risk; LIR: low-intermediate-risk; LR: low-risk; VHR: very-high-risk.

CUAJ • March-April 2016 • Volume 10, Issues 3-4

123

guy ꢆt ꢁꢇ.

100

Other

CON

SUR

Fig. 3. Patient management stratiﬁed by attendance in multidisciplinary clinic: (A) all treatments; (B) active treatments. CON: conservative therapy; RT: radiation

therapy; SUR: surveillance.

8%); of those choosing treatment, more chose RP than RT

primary ADT. While these numbers are not large, multiple

randomized, controlled trials have shown that compared to

RT and ADT, patients have an increased risk of PCa-related

(

81% vs. 19%, p<0.0001). The clinic’s mandate is to ensure

all of the patients diagnosed with PCa have a MDC appoint-

ment, regardless of how clear they are on their choice of

treatment to ensure they make a fully informed decision.

We could not force them to attend, but arranged their

MDC appointment so all the disciplines are readily avail-

able for them to take advantage of this unique opportunity.

Therefore, caution should be taken when interpreting these

differences, as MDC consult was not a random process (i.e.,

is associational not causational) and we didn’t collect age

and comorbidity data. It may well be that patients chose not

to attend a MDC because they were comfortable with their

decision (i.e., they knew they didn’t want radiation) or had

limited life expectancy based on comorbidities. However,

based on previous studies and our experience, patients

often have preconceived misconceptions about radiation

and beneﬁt from hearing about the logistics, success rates,

and side effects from a specialist trained in radiation oncol-

ogy, preferably one sub-specialized in PCa care. A simi-

lar study found that patient preferences had little effect on

treatment decisions. Rather, they were associated with the

specialty of the counseling physician. The GGWPC aims

to provide balanced information surrounding management

options in an open and interactive manner. It is important for

quality of life after treatment that patients receive balanced

information to make an informed decision and avoid post-

treatment regret.

indicate high patient satisfaction with this approach.

Of the 224 patients with high or very high risk, 13 (5.8%)

and 42 (18.8%) were also managed conservatively or with

3-25

and overall mortality

and combined modality treatment

should be offered. Obviously, some patients will have such

limited life expectancy that they would not beneﬁt from this

approach, but in our experience these patients are usually

not offered prostate screening.

Conclusions

In this large, Canadian, multidisciplinary DAP, the vast

majority of patients presented with screen-detected disease.

Over the observation window, there was a gradual shift from

LR to IR disease. Over 50% of patients who were candidates

for active surveillance were managed this way. Timely multi-

disciplinary consult was achievable in over 80% of patients

and was associated with different management decisions.

We recommend that all patients at risk for PCa be worked

up in a multidisciplinary DAP.

Competing interests: The authors declare no competing ꢀnancial or personal interests.

This paper has been peer-reviewed.

,21

In addition, reports from other MDCs

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CUAJ • March-April 2016 • Volume 10, Issues 3-4

Indication and clinical use:

Zoladex is indicated for the palliative treatment of

Diefenbach MA, Mohamed NE, Butz BP, et al. Acceptability and preliminary feasibility of an internet/

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Treatment with Zoladex and a non-steroidal

antiandrogen should start 8 weeks prior to initiating

radiation therapy and continue until completion of

the radiation therapy. The safety and effectiveness

of Zoladex in children has not been established.

Contraindications:

•

Hypersensitivity to goserelin/depot or any

component of the container

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Most serious warnings and precautions:

Osteoporosis: Assessment of osteoporosis risk

and management according to clinical practice and

guidelines should be considered.

Tumor ﬂare reaction: Patients at risk of developing

ureteric obstruction should be closely monitored

during the ﬁrst month of therapy. Patients with

vertebral metastases who are thought to be at

particular risk of spinal cord compression should be

closely monitored during the ﬁrst month of treatment.

Other relevant warnings and precautions:

•

Transient elevation of serum testosterone

concentrations

7. National Institute for Heath and Care Excellence: Prostate Cancer. Diagnosis and Treatment. January 2014.

https://www.nice.org.uk/Guidance/CG175. Accessed February 19, 2016.

•

Increased cardiovascular risk factors

Induced hypogonadism

Impaired glucose tolerance

Anemia

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dx.doi.org/10.1016/j.eururo.2012.03.053

Depression (sometimes severe)

• Pituitary-gonadal suppression

• Use in children has not been established; labeling

reﬂects safety and effectiveness in patients over

5 years of age

•

Treatment requires routine monitoring, physical

examinations and appropriate laboratory tests

For more information:

Please consult the Product Monograph for Zoladex at

www.azinfo.ca/zoladex/pm965 for important information

relating to adverse reactions, drug interactions and

dosing information. The Product Monograph is also

available by calling us at 1-800-565-5877.

4. Warde P, Mason M, Ding K, et al. Combined androgen-deprivation therapy and radiation therapy for

locally advanced prostate cancer: A randomized, phase 3 trial. Lancet 2011;378:2104-11. http://

dx.doi.org/10.1016/S0140-6736(11)61095-7

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advanced prostate cancer (SPCG-7/SFUO-3): An open, randomized, phase 3 trial. Lancet 2009;373:301-

. http://dx.doi.org/10.1016/S0140-6736(08)61815-2

Correspondence: Dr. Andrew Loblaw, Sunnybrook Health Sciences Centre, Toronto, ON, Canada;

andrew.loblaw@sunnybrook.ca

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