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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
Introduction : prostate cancer
What is prostate cancer?
Men only are affected by this disease!
4
Introduction : prostate cancer
What is prostate cancer?
5
Fig. 1: Prostate cancer localisation
(http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-what-is-prostate-cancer)
Introduction : 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
Introduction : prostate cancer
What is prostate cancer?
Possible pre-cancerous conditions of the prostate
7
Fig. 2: Zone of the prostate.
http://www.cancer.ca/en/cancer-information/cancer-type/prostate/anatomy-and-physiology/?region=on
Introduction : prostate cancer
What is prostate cancer?
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
Introduction : prostate cancer
What is prostate cancer?
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
Introduction : prostate cancer
What is prostate cancer?
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
Introduction : prostate cancer
What is prostate cancer?
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
Introduction : prostate cancer
What is prostate cancer?
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
Introduction : prostate cancer
What is prostate cancer?
D’Amico Risk Stratification for Prostate Cancer
13
Tab. 1 : Definition of the D’Amico Risk Stratification for Prostate Cancer [2]
Introduction : prostate cancer
What is prostate cancer?
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
Introduction : prostate cancer
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
Introduction : prostate cancer
Prostate cancer statistics:
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
Introduction : prostate cancer
Prostate cancer statistics:
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
Introduction : prostate cancer
Prostate cancer statistics:
Incidence and mortality
Estimated Canadian prostate cancer statistics (2015)
18
http://www.cancer.ca/en/cancer-information/cancer-type/prostate/statistics/?region=bc
Introduction : prostate cancer
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)
Introduction : prostate cancer
Incidence: How many people in Canada get prostate cancer?
20
Tab. 2: Lifetime probability of developing cancer overall and by age group, Canada, 2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Incidence: How many people in Canada get prostate cancer?
21
Tab. 2: Lifetime probability of developing cancer overall and by age group, Canada, 2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Incidence: How many people in Canada get prostate cancer?
22
Tab. 3: Annual percent change (APC) in age-standardized incidence rates for selected cancers, by sex,
Canada, 2001–2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Incidence: How many people in Canada get prostate cancer?
23
Tab. 3: Annual percent change (APC) in age-standardized incidence rates for selected cancers, by sex,
Canada, 2001–2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
** 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.
Introduction : prostate cancer
Mortality: How many people in Canada die of cancer?
24
Fig. 4: Age-standardized mortality rates (ASMR) cancers, males, Canada, 1986–2015
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Mortality: How many people in Canada die of cancer?
25
Tab. 4: Lifetime probability of dying from cancer overall and by age group, Canada, 2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Mortality: How many people in Canada die of cancer?
26
Tab. 4: Lifetime probability of dying from cancer overall and by age group, Canada, 2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Mortality: How many people in Canada die of cancer?
27
Tab. 5: Annual percent change (APC) in age-standardized mortality rates (ASMR) for selected cancers,
by sex, Canada, 2001–2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
Mortality: How many people in Canada die of cancer?
28
Tab. 5: Annual percent change (APC) in age-standardized mortality rates (ASMR) for selected cancers,
by sex, Canada, 2001–2010
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
** 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.
Introduction : prostate cancer
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
(http://www.cancer.ca)
Introduction : prostate cancer
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
(http://www.cancer.ca)
Introduction : prostate cancer
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
(http://www.cancer.ca)
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
Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada
(http://www.cancer.ca)
Introduction : prostate cancer
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]
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
41
Tab. 10: Cancer Status of Patients after 5 and 10 Years of Follow-up [1]
Results of permanent
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]
Results of permanent
Brachytherapy
Resent results of treatment
43
Fig. 12: (a) Overall survival for entire patient cohort (700 patients).
(b) Biochemical relapse-free survival (700 patients). [4]
a b
Results of permanent
Brachytherapy
Resent results of treatment
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
Results of permanent
Brachytherapy
Resent results of treatment
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]
Results of permanent
Brachytherapy
Resent results of treatment
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
Questions?
Thank you
53
54
Introduction : prostate cancer
What is prostate cancer?
Possible pre-cancerous conditions of the prostate
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
Introduction : prostate cancer
What is prostate cancer?
Possible pre-cancerous conditions of the prostate
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
Introduction : prostate cancer
What is prostate cancer?
Possible pre-cancerous conditions of the prostate
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
Introduction : prostate cancer
What is prostate cancer?
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

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Brachytherapy: Prostate Cancer

  • 1. BrachytherapyBrachytherapy :: prostate cancerprostate cancer Dumitru Loghin Ecole Polytechnique de Montréal Montréal autumn 2015 1
  • 2. 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
  • 3. 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
  • 4. Introduction : prostate cancer What is prostate cancer? Men only are affected by this disease! 4
  • 5. Introduction : prostate cancer What is prostate cancer? 5 Fig. 1: Prostate cancer localisation (http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-what-is-prostate-cancer)
  • 6. Introduction : 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. Introduction : prostate cancer What is prostate cancer? Possible pre-cancerous conditions of the prostate 7 Fig. 2: Zone of the prostate. http://www.cancer.ca/en/cancer-information/cancer-type/prostate/anatomy-and-physiology/?region=on
  • 8. Introduction : prostate cancer What is prostate cancer? 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
  • 9. Introduction : prostate cancer What is prostate cancer? 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
  • 10. Introduction : prostate cancer What is prostate cancer? 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
  • 11. Introduction : prostate cancer What is prostate cancer? 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
  • 12. Introduction : prostate cancer What is prostate cancer? 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
  • 13. Introduction : prostate cancer What is prostate cancer? D’Amico Risk Stratification for Prostate Cancer 13 Tab. 1 : Definition of the D’Amico Risk Stratification for Prostate Cancer [2]
  • 14. Introduction : prostate cancer What is prostate cancer? 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
  • 15. Introduction : prostate cancer 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
  • 16. Introduction : prostate cancer Prostate cancer statistics: 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
  • 17. Introduction : prostate cancer Prostate cancer statistics: 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
  • 18. Introduction : prostate cancer Prostate cancer statistics: Incidence and mortality Estimated Canadian prostate cancer statistics (2015) 18 http://www.cancer.ca/en/cancer-information/cancer-type/prostate/statistics/?region=bc
  • 19. Introduction : prostate cancer 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. Introduction : prostate cancer Incidence: How many people in Canada get prostate cancer? 20 Tab. 2: Lifetime probability of developing cancer overall and by age group, Canada, 2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 21. Introduction : prostate cancer Incidence: How many people in Canada get prostate cancer? 21 Tab. 2: Lifetime probability of developing cancer overall and by age group, Canada, 2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 22. Introduction : prostate cancer Incidence: How many people in Canada get prostate cancer? 22 Tab. 3: Annual percent change (APC) in age-standardized incidence rates for selected cancers, by sex, Canada, 2001–2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 23. Introduction : prostate cancer Incidence: How many people in Canada get prostate cancer? 23 Tab. 3: Annual percent change (APC) in age-standardized incidence rates for selected cancers, by sex, Canada, 2001–2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca) ** 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.
  • 24. Introduction : prostate cancer Mortality: How many people in Canada die of cancer? 24 Fig. 4: Age-standardized mortality rates (ASMR) cancers, males, Canada, 1986–2015 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 25. Introduction : prostate cancer Mortality: How many people in Canada die of cancer? 25 Tab. 4: Lifetime probability of dying from cancer overall and by age group, Canada, 2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 26. Introduction : prostate cancer Mortality: How many people in Canada die of cancer? 26 Tab. 4: Lifetime probability of dying from cancer overall and by age group, Canada, 2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 27. Introduction : prostate cancer Mortality: How many people in Canada die of cancer? 27 Tab. 5: Annual percent change (APC) in age-standardized mortality rates (ASMR) for selected cancers, by sex, Canada, 2001–2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 28. Introduction : prostate cancer Mortality: How many people in Canada die of cancer? 28 Tab. 5: Annual percent change (APC) in age-standardized mortality rates (ASMR) for selected cancers, by sex, Canada, 2001–2010 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca) ** 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.
  • 29. Introduction : prostate cancer 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 (http://www.cancer.ca)
  • 30. Introduction : prostate cancer 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 (http://www.cancer.ca)
  • 31. Introduction : prostate cancer 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 (http://www.cancer.ca)
  • 32. 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 Analysis by: Surveillance and Epidemiology Division, CCDP, Public Health Agency of Canada (http://www.cancer.ca)
  • 33. Introduction : prostate cancer 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.
  • 34. Brachytherapy Permanent brachytherapy is a type of prostate cancer treatment which is done by computer assisted implantation of radioactive isotope into the prostate. 34
  • 35. Brachytherapy 35 Fig. 7: Radioactive prostate seed (http://www.montereybayurology.com/urocond/prostateseedimplantintro.htm)
  • 36. 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/
  • 37. Brachytherapy Permanent seed implantation 37 Tab. 8: The isotopes used in permanent therapy
  • 38. 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
  • 39. 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
  • 40. 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]
  • 41. 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 41 Tab. 10: Cancer Status of Patients after 5 and 10 Years of Follow-up [1]
  • 42. Results of permanent 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]
  • 43. Results of permanent Brachytherapy Resent results of treatment 43 Fig. 12: (a) Overall survival for entire patient cohort (700 patients). (b) Biochemical relapse-free survival (700 patients). [4] a b
  • 44. Results of permanent Brachytherapy Resent results of treatment 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
  • 45. Results of permanent Brachytherapy Resent results of treatment 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]
  • 46. Results of permanent Brachytherapy Resent results of treatment 46 Tab. 13: Studies with large samples of patients with clinically localized prostate cancer treated with permanent prostate brachytherapy as monotherapy. [4]
  • 47. 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
  • 48. 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
  • 49. 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
  • 50. 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
  • 51. 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
  • 52. 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
  • 54. 54
  • 55. Introduction : prostate cancer What is prostate cancer? Possible pre-cancerous conditions of the prostate 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
  • 56. Introduction : prostate cancer What is prostate cancer? Possible pre-cancerous conditions of the prostate 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
  • 57. Introduction : prostate cancer What is prostate cancer? Possible pre-cancerous conditions of the prostate 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
  • 58. Introduction : prostate cancer What is prostate cancer? 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
  • 59. 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
  • 62. 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
  • 63. 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
  • 64. 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