Brachytherapy: Prostate Cancer

BrachytherapyBrachytherapy ::
prostate cancerprostate cancer
Dumitru Loghin
Ecole Polytechnique de Montréal
Montréal autumn 2015
1

2
Plan:Plan:
1.1.Introduction of prostate cancerIntroduction of prostate cancer
2.2.BrachytherapyBrachytherapy
3.3.Results of permanent BrachytherapyResults of permanent Brachytherapy
4.4.DiscussionDiscussion
5.5.ConclusionConclusion
6.6.ReferencesReferences

Introduction : prostate cancer
What is prostate cancer?
In prostate cancer a malignant tumor starts
to grows in prostate gland. Prostate cancer is the
most common type of cancer among Canadian
men. It usually grows slowly and often it can be
completely removed or managed successfully.
Malignant means that it can spread, or metastasize, to other
parts of the body.
3

Men only are affected by this disease!
4

5
Fig. 1: Prostate cancer localisation
(http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-what-is-prostate-cancer)

Possible pre-cancerous conditions of the prostate
•Prostatitis and benign prostatic
hyperplasia (BPH)
•Prostatic intraepithelial neoplasia (PIN)
•Proliferative inflammatory atrophy (PIA)
•Atypical small acinar proliferation (ASPA)
6

7
Fig. 2: Zone of the prostate.
http://www.cancer.ca/en/cancer-information/cancer-type/prostate/anatomy-and-physiology/?region=on

The cancer name is named by type of cells are found in the prostate
•Adenocarcinoma ~95%
•Sarcomas
•Small cell carcinomas
•Neuroendocrine tumors
•Transitional cell carcinomas
8

Risk factors for prostate cancer
9
Known risk factor Possible risk factors*
•Family history •A diet high in fat and dairy products
•A diet high in red or processed meats
•Being overweight or obese
•Inherited gene mutations
•Inflammation of the prostate
•Exposure to high levels of testosterone
•Tall adult height
•Exposure to pesticides
•Occupational exposures

Signs and symptoms of prostate cancer
-Early prostate cancer usually has NO SYMPTOMS !
-Advanced prostate cancers can sometimes cause symptoms, such as:
•Problems in urination
•Blood in the urine
•Erectile dysfunction
•Pain in the hips, back (spine), chest (ribs), or other areas like
bones that cancer has spread to them
•Weakness or numbness in the legs or feet, or even loss of bladder
or bowel control because cancerous tumor is pressing on the
spinal cord.
10

How is prostate cancer diagnosed?
•Medical history and physical exam (digital rectal exam DRE)
•PSA blood test (Prostate-Specific Antigen)
•Transrectal ultrasound (TRUS)
•Prostate biopsy
•Bone scan
•Computed tomography (CT) scan
•Magnetic resonance imaging (MRI)
•ProstaScintTM
scan
•Lymph node biopsy
11

What are the stages of prostate cancer?
Stage of cancer is the most important factors in choosing
treatment options and predicting a man’s outlook.
The < AJCC -TNM > staging system
American Joint Committee on Cancer
•T category: the extent of the primary tumor
•N category: whether the cancer has spread to nearby lymph nodes
•M category: the absence or presence of distant metastasis
•The PSA level at the time of diagnosis
•The Gleason score, based on the prostate biopsy
12

D’Amico Risk Stratification for Prostate Cancer
13
Tab. 1 : Definition of the D’Amico Risk Stratification for Prostate Cancer [2]

What are the stages of prostate cancer?
Staging is used to describe how far prostate cancer has spread
(metastasized) :
Stage I: Cancer is small and still within the prostate.
Stage II: Cancer is more advanced, but still confined to the
prostate.
Stage III: Cancer has spread to the outer part of the prostate and
nearby seminal vesicles.
Stage IV: Cancer has spread to lymph nodes, nearby organs or
tissues such as the bladder or rectum, or distant organs such as
bones or lungs.
14

Prostate cancer statistics:
Survival rates for prostate cancer
According to the most recent data, when including all stages of
prostate cancer:
•The relative 5-year survival rate is almost 100%
•The relative 10-year survival rate is 99%
•The 15-year relative survival rate is 94%
Keep in mind that just as 5-year survival rates are based on patients diagnosed and first
treated more than 5 years ago, 10-year survival rates are based on patients diagnosed
more than 10 years ago
15

Survival rates for prostate cancer
5-year relative survival by stage at the time of diagnosis
16
Stage 5-year relative survival rate
local nearly 100 %
regional nearly 100 %
distant 28 %
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates

Incidence and mortality
Estimated Canadian prostate cancer statistics (2015)
17
Category Males
New cases 24,000
Incidence rate (for every 100,000 people) 99
Deaths 4,100
Death rate (for every 100,000 people) 17
5-year relative survival (estimates for 2006–2008) 99 %
http://www.cancer.ca/en/cancer-information/cancer-type/prostate/statistics/?region=bc

Incidence and mortality
Estimated Canadian prostate cancer statistics (2015)
18
http://www.cancer.ca/en/cancer-information/cancer-type/prostate/statistics/?region=bc

Incidence: How many people in Canada get prostate cancer?
19
Fig. 3: New cases and age-standardized incidence rates (ASIR) for all cancers, Canada, 1986–2015
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)

20
Tab. 2: Lifetime probability of developing cancer overall and by age group, Canada, 2010

21
Tab. 2: Lifetime probability of developing cancer overall and by age group, Canada, 2010

22
Tab. 3: Annual percent change (APC) in age-standardized incidence rates for selected cancers, by sex,
Canada, 2001–2010

23
Tab. 3: Annual percent change (APC) in age-standardized incidence rates for selected cancers, by sex,
Canada, 2001–2010
** Significant increase or decrease in APC, p<0.01.
† APC is calculated assuming a piecewise log linear model. The model
was fitted to the rates in 1986–2010.

Mortality: How many people in Canada die of cancer?
24
Fig. 4: Age-standardized mortality rates (ASMR) cancers, males, Canada, 1986–2015

25
Tab. 4: Lifetime probability of dying from cancer overall and by age group, Canada, 2010

26
Tab. 4: Lifetime probability of dying from cancer overall and by age group, Canada, 2010

27
Tab. 5: Annual percent change (APC) in age-standardized mortality rates (ASMR) for selected cancers,
by sex, Canada, 2001–2010

28
Tab. 5: Annual percent change (APC) in age-standardized mortality rates (ASMR) for selected cancers,
by sex, Canada, 2001–2010
** Significant increase or decrease in APC, p<0.01.
† APC is calculated assuming a piecewise log linear model. The model
was fitted to the rates in 1986–2010.
‡ Changepoint indicates the baseline year for the APC shown, if the
slope of the trend changed after 2001.

Relative survival:What is the likelihood of surviving cancer?
29
Fig. 5: One-, three-, five- and ten-year relative survival ratios (RSRs) for the most common cancers,
ages 15–99 at diagnosis, Canada (excluding Quebec*), 2006–2008
Analysis by: Surveillance and Epidemiology Division, Statistic Canada

Relative survival:What is the likelihood of surviving cancer?
30
Tab. 6: Tumor-based prevalence for selected cancers by prevalence duration and sex, Canada, January1, 2009
Analysis by: Canadian Cancer Registry database at Statistics Canada

Prevalence: How many people diagnosed with cancer are alive
today?
31
Tab. 7: Age distribution for 10-year tumour-based prevalence for the most common cancers by sex, Canada,
January 1, 2009
Analysis by: Canadian Cancer Registry database at Statistics Canada

Introduction
Predictions of the future burden of prostate cancer in Canada
32
Fig. 6: Age-standardized incidence rates (ASIRs) for prostate cancers, Canada, 1985–2030

Cost of Prostate CancerTherapy
First-year costs were lowest for watchful waiting ($4,270)
and highest for the hormone-radiation group ($17,474)
The total five-year costs were as follows:
•Watchful waiting, $9,130
•Radiation therapy only, $15,589
•Surgery, $19,214
•Hormone-radiation, $25,097
•Hormonal only, $26,896
33
Source Reference: Snyder CF et al. "How does initial treatment choice affect short-term and long-term costs
for clinically localized prostate cancer?" Cancer 2010; DOI: 10.1002/cncr.25517.

Brachytherapy
Permanent brachytherapy is a type of
prostate cancer treatment which is done
by computer assisted implantation of
radioactive isotope into the prostate.
34

Brachytherapy
35
Fig. 7: Radioactive prostate seed
(http://www.montereybayurology.com/urocond/prostateseedimplantintro.htm)

Brachytherapy
Permanent seed implantation
36
Fig. 8: Sagittal view of the Seattle low dose radiation seed implant technique for prostate cancer with the trans rectal probe
in situ, and the implant taking place via the trans perineal route through a template, the depth coordinate being called by the
rectal ultrasound probe.
http://www.prostatecancertreatment.co.uk/treatment-options/brachytherapy/

Brachytherapy
Permanent seed implantation
37
Tab. 8: The isotopes used in permanent therapy

Brachytherapy
Patients selection for permanent Brachytherapy as
monotherapy
• Gleason score < 8
• Gland volume < 50cc
• PSA < 15 ng/ml
Patients selection for permanent Brachytherapy with
external beam radiation or hormonal therapy
• Gleason score > 7
• Clinical stage > T2
• PSA < 20 ng/ml
[3]
38

Brachytherapy
Development of brachytherapy
•1960s, Scardino and Carlton at Baylor College of
medicine began treating prostate cancer utilizing
brachytherapy
(Scardino P, Carlton C. Combined interstitial and external irradiation for prostatic cancer. In: Javadpour N, ed.
Principles and Management of Urologic Cancer. Baltimore, Md:Williams &Wilkins; 1983:392-408.)
•1970s, Whitmore et al at Memorial Sloan-Kettering
Cancer Center also began to insert radioactive iodine-
125 (125I) seeds as a sole treatment
(Whitmore WF Jr, Hilaris B, Grabstald H. Retropubic implantation to iodine 125 in the treatment of prostatic cancer.
J Urol. 1972;108:918-920.)
39

Results of permanent
Brachytherapy
Earliest results of treatment
180 patients with surgical stage A2-C prostate cancer treated between
1976 and 1986 by radioactive gold seed implantation followed by
external irradiation
40
Tab. 9: Vital Status of Patients after 5 and 10 Years of Follow-up and at Study End-point [1]

Brachytherapy
Earliest results of treatment
180 patients with surgical stage A2-C prostate cancer treated between
1976 and 1986 by radioactive gold seed implantation followed by
external irradiation
41
Tab. 10: Cancer Status of Patients after 5 and 10 Years of Follow-up [1]

Brachytherapy
Resent results of treatment
Retrospective study of 700 patients with low-risk PCa, who underwent
trans_perineal ultrasound-guided iodine-125 permanent prostate brachytherapy
(145 Gy) between January_2000 and July_2012
42
Tab. 11: Clinical characteristics at baseline [4]

Brachytherapy
43
Fig. 12: (a) Overall survival for entire patient cohort (700 patients).
(b) Biochemical relapse-free survival (700 patients). [4]
a b

Brachytherapy
5 – 10 year rate of overall survival (OS) :
• 5 year: 94% (95% confidence interval [CI], 92-96%)
• 10 year: 84% (95% CI, 78-90%)
5 – 10 year rate of BRFS (Biochemical relapse-free survival ):
• 5 year: 95% (95% CI, 93-97%)
• 10 year: 85% (95% CI, 79-91%)
44

Brachytherapy
The BRFS by D’Amico risk group, without significant differences between
groups (p=0.810).
45
Fig. 9: Biochemical relapse-free survival by D’Amico risk group. [4]

Brachytherapy
46
Tab. 13: Studies with large samples of patients with clinically localized prostate cancer treated
with permanent prostate brachytherapy as monotherapy. [4]

Discussion
•Brachytherapy is used to treat prostate cancer for
more than 50 years.
•This treatment get best results in PSA nadir level
<1ng/ml
•It can be a common treatment method for all stages
of cancer
•It shows better results and less side effects than
external beam radiotherapy
•In compare with prostatectomy, the brachytherapy
keep functionality of prostate
•The majority of patients will be able to urinate
immediately after the procedure
47

Discussion
•The entry of needles in the perineum can cause
irritation and inflammation
•Hematuria
•Hematospermia
•Urinary symptoms
•Inflammation to the rectal mucosa
•Erectile dysfunction
•There is a risk for secondary malignancy and
exposure to radiotherapy
48

Discussion
• The future works are on effect of treatment on behavior of patient
after the procedure is done.
• Using a nomogram procedures to calculate the seed requirement
in advance of the implant: 4D Brachytherapy
49

Conclusion
The best method to treat the low risk prostate
cancer is the Brachytherapy as monotherapy which
shows good results in overall survivals and BRFS with
minimal and temporal sides effects. If the prostate
cancer is intermediate or high risk, to treat it can be
used the Brachytherapy along with external beam
radiotherapy or hormonotherapy.
50

Reference
[1].LONG-TERM RESULTS OF COMBINED INTERSTITIAL GOLD SEED
IMPLANTATION PLUS EXTERNAL-BEAM IRRADIATION IN LOCALIZED
CARCINOMA OF THE PROSTATE. By: LANNON, SG; ELARABY, AA; JOSEPH, PK; et al.
BRITISH JOURNAL OF UROLOGY  Volume: 72   Issue: 5   Pages: 782-
791   Part: 2   Published: NOV 1993
[2].Modern Brachytherapy for Treatment of Prostate Cancer. Randy V. Heysek, MD,
FACRO, Cancer Control, July 2007, Vol. 14, No. 3
[3].BC Cancer Agency prostate brachytherapy experience: Indications, procedure, and
outcomes. Mira Keyes, MD, FRCPC, James Morris, MD, FRCPC, Tom Pickles, MD,
FRCPC, Michael McKenzie, MD, FRCPC. Issue: BCMJ, Vol. 52, No. 2, March
2010, page(s) 76 - 83 Articles
[4].Permanent seed brachytherapy for clinically localized prostate cancer: Long-term
outcomes in a 700 patient cohort. Evelyn Martinez and Al.
http://dx.doi.org/10.1016/j.brachy.2014.11.015
[5].Brachytherapy for the Treatment of Prostate Cancer. Cesaretti, Jamie A, MD, MS; Stone,
Nelson N, MD     ; Skouteris, Vassilios M, MD; Park, Janelle L, MD     ; Stock,
Richard G, MD      . The Cancer Journal  13.5   (Sep/Oct 2007): 302-12.
[6].http://www.cancer.ca
[7].4D Brachytherapy, a novel real-time prostate brachytherapy technique using
stranded and loose seeds. Langley S E and Al. 2012 Feb;109 Suppl 1:1-6. doi:
10.1111/j.1464-410X.2011.10824.x.
51

Take Home Message
Even if prostate cancer is the most diagnosed
tumor, it doesn’t cause mortality as often than other
types of cancer. It is because the brachytherapy is the
best method to combat this disease and keep a high
level of life quality post treatment.
52

Prostatic intraepithelial neoplasia (PIN)
•It can be Multifocal
•It often found in the peripheral zone of the prostate
•It be either low or HIGH grade
Not all high-grade PIN sites will advance to prostate cancer during a man's lifetime.
55

Proliferative inflammatory atrophy (PIA)
PIA is characterized by abnormal epithelial cells that are dividing
more rapidly in areas of chronic inflammation.
Areas of the prostate with PIA changes are 20% more likely to
develop prostate cancer.
56

Atypical small acinar proliferation (ASAP)
ASAP is abnormal growth of gland cells that can change into
prostate cancer. In men with ASAP, the likelihood of finding prostate
cancer in a future biopsy sample is about 40–50%40–50%.
57

Do we know what causes prostate cancer?
1. Inherited DNA mutations
•RNASEL (formerly HPC1)
•BRCA1 and BRCA2
•DNA mismatch repair genes (such as MSH2 and MLH1)
2. DNA mutations acquired during a
man’s lifetime
58

Brachytherapy
History of Prostate Seed Implant
In 1910,Young used intra-urethral radium for the treatment of
prostate cancer
In 1930, Flocks first injected radioactive gold liquid into the prostate
for the treatment of prostate cancer
In the early 1970s, physicians at Memorial Sloan Kettering Cancer
Center in NewYork were the first to perform prostate seed implants,
using iodine seeds
In 1983 Holm performed the first "closed" implant, using needles
and ultrasound guidance
In 1985 Ragde, Blasko, and Grimm modified Holm's technique and
began to perform prostate seed implantation in Seattle
59

Brachytherapy
60
http://knoxvilleurology.com/patient-education/da-vinci-surgery-vs.-open-surgery-vs.-laparoscopic

Prostate Cancer
61
http://www.cancer.gov/types/prostate/patient/prostate-treatment-pdq

Stage
•T categories (clinical)
•There are 4 categories for describing the local extent of a prostate tumor, ranging fromT1 toT4.
Most of these have subcategories as well.
•T1: Your doctor can’t feel the tumor or see it with imaging such as transrectal ultrasound.
• T1a: Cancer is found incidentally (by accident) during a transurethral resection of the prostate (TURP)
that was done for benign prostatic hyperplasia (BPH). Cancer is in no more than 5% of the tissue
removed.
• T1b: Cancer is found during aTURP but is in more than 5% of the tissue removed.
• T1c: Cancer is found by needle biopsy that was done because of an increased PSA.
•T2:Your doctor can feel the cancer with a digital rectal exam (DRE) or see it with imaging such as
transrectal ultrasound, but it still appears to be confined to the prostate gland.
• T2a:The cancer is in one half or less of only one side (left or right) of your prostate.
• T2b:The cancer is in more than half of only one side (left or right) of your prostate.
• T2c:The cancer is in both sides of your prostate.
•T3: The cancer has grown outside your prostate and may have grown into the seminal vesicles.
• T3a:The cancer extends outside the prostate but not to the seminal vesicles.
• T3b:The cancer has spread to the seminal vesicles.
•T4:The cancer has grown into tissues next to your prostate (other than the seminal vesicles), such
as the urethral sphincter (muscle that helps control urination), the rectum, the bladder, and/or the
wall of the pelvis.
62

Stage
• N categories
• N categories describe whether the cancer has spread to nearby
(regional) lymph nodes.
• NX: Nearby lymph nodes were not assessed.
• N0:The cancer has not spread to any nearby lymph nodes.
• N1:The cancer has spread to one or more nearby lymph nodes.
• M categories
• M categories describe whether the cancer has spread to distant parts
of the body.The most common sites of prostate cancer spread are to
the bones and to distant lymph nodes, although it can also spread to
other organs, such as the lungs and liver.
• M0:The cancer has not spread past nearby lymph nodes.
• M1:The cancer has spread beyond the nearby lymph nodes.
• M1a:The cancer has spread to distant (outside of the pelvis) lymph nodes.
• M1b: The cancer has spread to the bones.
• M1c: The cancer has spread to other organs such as lungs, liver, or brain (with
or without spread to the bones).
63

Stage grouping
• Stage I: One of the following applies:
• T1, N0, M0, Gleason score 6 or less, PSA less than 10
• T2a, N0, M0, Gleason score 6 or less, PSA less than 10
• Stage IIA: One of the following applies:
• T1, N0, M0, Gleason score of 7, PSA less than 20
• T1, N0, M0, Gleason score of 6 or less, PSA at least 10 but less than 20
• T2a orT2b, N0, M0, Gleason score of 7 or less, PSA less than 20
• Stage IIB: One of the following applies:
• T2c, N0, M0, any Gleason score, any PSA
• T1 orT2, N0, M0, any Gleason score, PSA of 20 or more
• T1 orT2, N0, M0, Gleason score of 8 or higher, any PSA
• Stage III:
• T3, N0, M0, any Gleason score, any PSA
• Stage IV: One of the following applies:
• T4, N0, M0, any Gleason score, any PSA
• AnyT, N1, M0, any Gleason score, any PSA
• AnyT, any N, M1, any Gleason score, any PSA
64

Brachytherapy: Prostate Cancer

Brachytherapy: Prostate Cancer

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