This presentation is about the updated guidelines on management of Localized prostate cancer

1. Approach to a case of
localized prostate cancer
Dr Santosh K
Senior Resident
All India Institute of Medical Sciences , Bhubaneswar

2. Need for this discussion
Following diagnosis- multitude of care options available
• Active surveillance
• Observation/watchful waiting
• Prostatectomy
• Radiotherapy
• Cryosurgery
• High intensity focused ultrasound (HIFU)
• Focal therapy
• Influenced by patient factors(longevity) and by cancer severity or aggressiveness
• Categorization patients based on cancer aggressiveness -facilitates care decisions

3. Introduction
• Prostate cancer - Second most common cancer
• Sixth leading cause of cancer deaths worldwide
• Prostate cancer rarely causes symptoms at an
early stage
What is a localized prostate cancer??
Cancer that’s inside the prostate and hasn’t
spread to other parts of the body
“Early” or “Organ-confined prostate cancer”
Stage T1 or T2 prostate cancer

4. • Method of diagnosis of localized prostate cancer has changed since 1980
• Most localized prostate cancers are diagnosed by PSA suspected TRUS guided biopsy
• Nonpalpable cancers now account for 60% to 75% of diagnosis
• Effect of widespread PSA and DRE screening :
• Stage migration- 81% of newly diagnosed -localized disease
• Earlier age of detection(7067 Yrs)
• Metastatic disease incidence decreased by 75%
• Improvements in 5-year disease-specific survival
• Average age of death- stable over the last three decades (77 years)

5. PSA Screening for prostate cancer
• Men who present for periodic health examinations should be made aware of the benefits
and risks of PSA screening so that they can make an informed decision whether to be
screened
• The interpretation of PSA values should always take into account age, the presence of
urinary tract infection ,recent diagnostic procedures, and prostate-directed treatments.
• The probability of detecting prostate cancer on biopsy increases directly with
PSA across the full spectrum of PSA levels

6. • PSA Density: PSAD of 0.15 or greater is proposed for recommending prostate biopsy in
men with PSA levels between 4 and 10 ng/mL and normal DRE
• Prostate-Specific Antigen Velocity: PSAV greater than 0.75 ng/mL/yr. is a specific marker
for the presence of prostate cancer in men with PSA levels between 4 and 10 ng/mL
• Free Prostate-Specific Antigen. PSA in men with prostate cancer escapes proteolysis and
therefore a lower percentage of free (unbound) form.
• Prostate-Specific Antigens Isoforms
• Human Kallikrein 2
• Multiplex Tests: PHI(tPSA,fPSA and -2proPSA)
4K score( tPSA,fPSA,iPSA,hk2)

7. PSA Screening for prostate cancer
• Randomized trials emphasize-overdiagnosis and overtreatment with screening
• USPSTF - insufficient evidence to assess the balance of benefit and harm of screening
among men 75 years of age or younger.
-Screening is not recommended for men 75 years of age or older.
• American College of Preventive Medicine –insufficient evidence to recommend routine
population screening with PSA and DRE . Men should be given information about benefits
of PSA screening.

8. • AUA recommends shared decision making about screening for men 55 to 69 years of age.
• National Comprehensive Cancer Network recommends starting a risk to benefit discussion and
offering baseline PSA screening at 45 years of age with the frequency of follow-up testing based
on PSA test results (1- to 4-year intervals).
• European Association of Urology recommends a risk-adapted approach based on the initial PSA
level for well-informed men with good performance status and a 10- to 15-year life expectancy.
“urologist’s recommendation for screening and treatment, however,
continues to have the most influence on decision making”
Davison BJ, Breckon E: Factors influencing treatment decision making and information preferences of prostate cancer patients on active surveillance, Patient Educ
Couns 87:369, 2012

9. Digital Rectal Examination
• Most urologists use PSA and DRE together for prostate cancer detection.
• PSA testing improves the positive predictive value (PPV) of DRE for cancer.
• Clinical tumour staging

10. Triggers for Biopsy
• PSA level that is considered suspicious - should be remeasured
• PSA together with other methods of risk assessment, such as family history, race, and DRE
findings.
• Initially approved: >4ng/ml, studies- 2.5 ng/ml
• For PSA 4-10, fPSA<10%
• PSA 4-10 , PSAV >0.75 ng/dl/year
• DRE suspicious nodule

11. IMAGING
• USG:Doppler may characterize tissue based on blood flow pattern
Histoscanning- computer aided scanning to characterize abnormal tissue
• MRI: Evaluated for many years for T staging
DW MRI and Dynamic contrast enhanced MRI to know locoregional extent
MRI TRUS fusion biopsy
mp-MRI- Target biologically significant tumours
• Cross sectional imaging for LN involvement: Not recommended for localized prostate cancer
• Bone scan: PSA>20 ng/ml
Gleason score 8-10

12. Range of localized Carcinoma Prostate
• Seemingly localized tumors
• Low malignant potential - left untreated are unlikely to result in morbidity or reduce
life expectancy
• Curable with a single modality directed exclusively to the gland itself
• Those destined to recur locally or systemically despite optimal local therapy.
• Last category encompasses tumors that are broadly classified as “high-risk”.

13. Longevity assessment
NCCN-“Life expectancy estimation is critical to informed decision-
making in prostate cancer early detection and treatment.”

14. Longevity nomograms with comorbidities
• Charlson Co-morbidity Index (CCI) -designed to weigh comorbidities
in prediction of 1-year mortality among inpatients.
• Prostate cancer–specific CCI (PCCI) - weighs comorbidities to predict
10-year risk of mortality among prostate cancer patients

15. Baseline Urinary, Sexual, and Bowel Function
• Critical considerations as they influence the magnitude of benefit and
risk to the patient with regard to quality of life
• International Prostate Symptom Score (IPSS)
• UCLA Prostate Cancer Index

16. Tools for risk stratification

17. Prognostic factors
• Gleason Score
• Tumor Stage
• Baseline PSA
• % involvement of a biopsy core

19. Gleason score

20. Gleason score and ISUP grades

21. The 15-year risk of dying from PCa in relation to Gleason score at
diagnosis in patients with localised disease aged 55-74 years
Gleason score Risk of cancer death
(%)
2-4 4-7
5 6-11
6 18-30
7 42-70
8-10 60-87
Albertsen PC et al. JAMA 1998;280(11): 975-80

22. What is a significant Cancer
• Long term(>30 yrs) follow up study( Popiolek et al, 2013) – in untreated localized cancer
• significant risk of cancer progression
• Increased prostate cancer specific death
• Statistical models – to detect indolent tumours- for survillance

23. • Kattan et al
• Organ confined
• Tumour volume less than 0.5 ml
• Without poorly differentiated elements
Other factors to exclude:
African American race
BRCA2 mutation positive individuals
At present no tumour marker or algorithm can identify indolent tumour with
certainty

24. Risk stratification -D'Amico Risk groups
Low risk Intermediate risk High risk
T1-T2a
Gleason 2-6
PSA <10
T2b
Gleason 7
PSA 10-20
≥T2c
Gleason ≥8
PSA >20

25. D’amico classification and risk of PSA failure at 5
years
≤T2a
Gleason ≤6
PSA<10 ng/ml
Low risk
<25%
T2b
Gleason 7
PSA 10-20 ng/ml
Intermediate risk
25-50%
≥ T2c
Gleason 8-10
PSA >20 ng/ml
High risk
>50%

27. EAU risk groups

28. Genomic risk stratification
• Liquid biopsies – Easy to test
• Prostate Health Index (PHI)
• 4Kscore test
• prostate cancer antigen 3 (PCA3)
• Mi-Prostate Score
• Select MDx
• ExoDx Prostate Intelliscore
• Tissue-based assays - gold standard
• Confirm MDx
• Polaris
• Decipher
• Oncotype Dx GPS
(AUA)/ (ASTRO)/ (SUO) guidelines for management of clinically localized prostate cancer state that among most
low-risk prostate cancers, tissue-based genomic biomarkers have not shown a clear role in the selection of
candidates for active surveillance

29. Nomogram for Prediction of pathological Stage-
Partin table

30. Nomogram for predicting clinical outcome
• UCSF Cancer of the Prostate Risk Assessment (CAPRA) score was
developed for the prediction of clinical outcomes using age, PSA level,
clinical stage, biopsy Gleason score, and percentage of positive biopsy
cores

31. Counseling of patients - (Strong recommendation;
Evidence level: grade A)
should incorporate shared decision making and explicitly consider
• Cancer severity (risk category)
• Patient values and preferences
• Life expectancy
• Pretreatment general functional and genitourinary symptoms
• Expected post treatment functional status
• Potential for salvage treatment. (Strong recommendation; Evidence
level: grade A)

32. • Modifiable health-related behaviors or risk factors, such as smoking
and obesity
• Should inform patients about suitable clinical trials and encourage
patients to consider participation in such trials based on eligibility and
access. (Expert Opinion)

33. Meet with different prostate cancer care
specialists –Uro,MO,SO,RO
To know about morbidity and mortality
• Surgery- Urinary incontinence(25%), Erectile dysfunction
• RT- Enteritis, Proctitis, Erectile dysfunction ,Urinary frequency,
dysuria, urgency
• Brachytherapy- Stricture, Retention , incontinence

34. Treatment Methods
• Active surveillance/Watchful waiting
• Radical Prostatectomy
• Radiation therapy
• Androgen deprivation
• Focal therapy

35. Deferred treatment
• Watchful waiting refers to monitoring the patient until he develops metastases that
require palliative treatment.
• Life expectancy < 10 years
• Low grade (Gleason score 2-6)
• Active surveillance - delayed primary treatment till there is biochemical or histologic
evidence of cancer progression. Strategy to delay treatment that might not be
immediately necessary.
• Low volume
• Low/ intermediate grade( Up to Gleason score 3+4=7)

37. Follow up of patients
• Semi annual PSA
• Semi annual DRE
• Annual biopsies
• Absence of cancer on repeated biopsy significantly reduces the likelihood of progression
• In most studies 25-50 % developed evidence of tumour progression with in 5 years
• 30-92% in various studies had curable cancer at the time of disease progression

38. Outcome measure
• long-term OS and CSS for patients
on AS are extremely good
• More than one-third of patients
are ‘re-classified’ during follow-
up
• Most of whom require curative
treatment due to disease
upgrading, increase in disease
extent, disease stage, progression
or patient preference.

39. When to intervene
Intervention is required( in healthy patient with life expectancy >10 years) if :
• Gleason pattern 4-5
• More than 2 core biopsies are involved
• More than 50% of the biopsy core is involved
• PSA velocity > 0.35ng/ml/year
• Patient’s choice

40. Demerit of conservative management
• A substantial population of those with potentially curable disease
destined to progress, managed with surveillance, will require multiple
extended biopsy procedures- infections,cause ED, complicate
subsequent attempts at nerve sparing surgery or delay treatment
until the window of opportunity for cure has closed

41. Radical Prostatectomy
• Morbid procedure
• No treatment has supplanted RP- still remains gold standard
• Hormonal / chemotherapy are never curative
• Not all cancer cells are eradicated by RT and focal therapy
• Chance of denovo carcinogenesis in left out tissue after focal therapy
Advantage of RP:
• Possibility of cure
• Minimum collateral damage when done skillfully
• More accurate pathological staging of cancer
• Treatment failure is more readily identified
• Potentially curative RT can be started at the earliest.

42. Disadvantages :
• Long hospitalization and recovery period
• Possibility of incomplete tumour resection
• ED/ urinary incontinence
Surgical Approaches:
Perineal
Trans abdominal
Laproscopic /Robot assisted

43. • Long-term outcome of cancer control is better documented for open prostatectomy
• Challenging to fairly compare functional outcomes among surgical techniques
• inherent selection bias in these retrospective studies
• baseline comorbidities

44. Patient selection
• Healthy and free of comorbidities that might make the operation
unacceptable
• Life expectancy of at least 10 years
• Tumor should be deemed to be biologically significant and completely
resectable
• Accepted upper age limit -76 years
• Older men have a greater risk for prostate cancer–specific death, despite
higher death rates from competing causes
• Imaging studies are not accurate for staging prostate cancer
• Preoperative clinical and pathologic parameters -predict the pathologic
stage and identify patients most likely to benefit from RP

45. Patient selection
• Neoadj hormonal and chemotherapy have no benefits
• Nerve sparing technique should be used

46. Outcome measure
• overall 25-year progression-free 68%,
• metastasis-free 84%,
• cancer-specific survival rates were 86%
• significant differences in men treated in the pre-PSA and PSA eras.
• Radical prostatectomy provides long-term cancer control in men
with high-risk disease or locally advanced disease

47. FOLLOW UP
• Biochemical failure precedes clinical symptoms
• Detectable PSA(>0.1 ng/dl) after radical prostatectomy – Persistant
disease or left out benign tissue
• PSA velocity helps differentiate both
• PSA Velocity, interval from surgery to biochemical recurrence and
Gleason score reflect rapidity of tumour progression
• SALVAGE RT to be started PSA<0.5ng/ml, beneficial effects are
Adjuvant RT is questionable
• ADT after RP: Low data available about benefit
• RT+ADT: survival advantage in High risk cancer in healthy individuals

48. Radiotherapy
• External beam/ brachy therapy/ Heavy particle
• IMRT- 3D Conformal radiotherapy
• Dose escalation and 3D definition improve results
• Low risk- 70-72 Gy
• Intermediate risk 75-76 Gy
• High risk 80 Gy

49. Side effects
• Related to injury to the microvasculature of the bladder, rectum, striated sphincter
muscle, and urethra
• One third of patients experience acute symptoms of proctitis or cystitis during the course
of radiotherapy-after the dose exceeds 50 Gy.
• About 5% to 10% have permanent symptoms, such as
• irritable bowel syndrome
• intermittent rectal bleeding
• bladder irritability
• intermittent gross hematuria

50. • Prior transurethral resection of the prostate – relative contraindication to brachytherapy
and external beam radiation Therapy
• Severe obstructive urinary symptoms -relative contraindication -risk of acute urinary
retention,
• Inflammatory bowel disease- relative contraindication
• One half of patients develop erectile dysfunction
• Reduced vasculature of the cavernous nerves and of the corpora cavernosa of the penis

51. Assessment of treatment end point
• PSA gradually reduces over 2-3 years
• Monitored at 6 monthly intervals until it reaches nadir
• No absolute nadir value or time to Nadir defined
• Accepted values are PSA< 0.5ng/ml In 18 months time
• PSA bounce- within 2 years of RT
• Pheonix Definition if treatment failure- NADIR+2
• 10 years cancer cure – 50%
• 5 years progression free survival- 70-85%

52. Other therapies
• Thermal ablation
• Cryo therapy
• HIFU
• LASER ablation

53. Comparative Population-Based Studies

58. EAU 2018 low risk

61. EAU 2018

64. EAU 2018