LOCALIZED PROSTATE

CA
MOATH ALHARBI
 BACKGROUND

• Prostate cancer is the most common noncutaneous cancer and

the second leading cause of death from cancer in men in the US.
• Among men alive today 12.9 % will be diagnonsed by prostate
cancer , 2.5 % will die from it .
• In 2020, it was estimated that 191,930 new cases would occur in
US; it would be the cause of death for 33,330 men
 BACKGROUND

• The prevalence of prostate cancer increases

strikingly with age.

• Prostate cancer incidence and deaths have

increased in the past few years, PCa deaths
increasing from an estimated 26,730 in
2017 to 31,620 in 2019 to 33,330 in 2020

• 1990’s peak attributed to the widespread of

PSA screening
 EPIDEMIOLOGY

• Prostate cancer is rarely diagnosed in men younger than 50 years of age, accounting for only 2% of all cases .

• Before the PSA era, the median age at diagnosis was 70, falling to 67 over the past decade, with 63% diagnosed after 65 years
of age .

• The average age of death from prostate cancer is 77 years of age .

• PSA has induced a significant downward migration in age and stage (both clinical and pathologic) at diagnosis.
 Risk Factor

• Evidence suggests that both genetics and environment play a role in the origin and evolution of prostate cancer.

• Epidemiologic and molecular evidence suggests that prostate cancer has as strong familial component as demonstrated by
epidemiologic studies and germline genetic analysis.
 Risk Factor

• Histologic evidence of inflammation, as manifested by proliferative inflammatory atrophy, is common in prostate cancer and
may represent a key pathobiologic process in its development.

• Epidemiologic data suggest that a history of sexually transmitted infection or prostatitis is associated with a higher risk of
prostate cancer.
 Risk Factor

• Androgens influence the development, maturation, and maintenance of the prostate, affecting both proliferation and
differentiation of the luminal epithelium.

• Exposure of the prostate to androgens at key developmental times plays an important role in prostate carcinogenesis .

• Estrogens have both direct and indirect effects on prostatic growth and development and likely play a role in prostate cancer
initiation and progression

• No association between (smoking , high fat diet ) with prostate cancer .

 PSA

• Member of the human kallikrein 3 gene family

• Released from prostatic epithelium .

• Found in seminal fluid and serum .

• Ectopic expressed by breast tissue , breast cancer , adrenal and renal carcinoma .

• The half-life is around 2-3 days .

• Expressed by androgen .

• 70 % of PSA found to be bounded by protein .

• No cutoff normal level of PSA

 PSA
FACTORS MAY AFFECT PSA VALUE

• Reducing PSA (may cause False -ve) : • Increasing PSA:

• Race • Race or genetic

• Androgen Status ( hypogonadism and obesity) • Age

• Medications (Statin and 5-alpha reductase): Adjust the value

• Prostate volume (increases 4% per milliliter of prostate
by X2.3 @2 yrs and X2.5 @7 yrs
volume)
• BPH (5-alpha reductase and Surgical)
• Prostate disease (PCa, BPH and prostatitis)
• PCa treatment (surgical or medical )
• Manipulation OR Trauma ( Cystoscopy , Prostatic massage
• Obesity , Prostate biopsy , extensive ambulation or cycling )

• Ejaculation ?
 PSA KINETICS

• PSA Velocity = Needs 3 readings of PSA with intervals of 6

months in between

• PSA 4-10 ng/mL: >0.75 ng/mL/year

• PSA <4 ng/mL: >0.4 ng/mL/year

• PSA DENSITY (PSAD) = PSA divided by prostate volume

• For normal DRE and PSA 4-10 ng/mL to differentiate

between BPH and PCa

• PSAD >0.15 —> more risk of PCa

PSA for screening and Early detection
 Urine PCA3(prostate cancer antigen)

• One of most sensitve and sepcifc test for prostate cancer .

• No expressed out side the prostate ,

• Improve performance over the PSA

• Collected after DRE

• Approved by FDA 2012

 PROSTATE BIOPSY

TRUS prostate biopsy is sensitive comparing to DRE and PSA level to diagnose prostate cancer .

• Indications:

• Rising or persistent increased PSA levels;

• Abnormal findings on DRE, TRUS, and MRI imaging .

• Previous biopsy showing multifocal high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar
proliferation (ASAP)
 PROSTATE BIOPSY

• Sextant biopsy of prostate is inadequate to diagnose prostate cancer

• Extended 12 core biopsy is recommneded by AUA to diagnose prostate ca .

• Anticoagulant (warfarin,clopedgrel) should be stopped 7-10 day before .

• Revaroxiban, epixiban should be stopped 2-5 days before

• Low dose asprin does not need to be discontinued .

• Prophylaxis antimicrobial is recommended for all patient (new AUA , Fluoroquinolones 24hours
before )
 PROSTATE BIOPSY

• Contraindication:
Signifcant coagulopathy .
Sever immunosuppression
Acute prostatitis

Complications :
 PROSTATE BIOPSY
BIOPSY IS NOT ONLY Gleason Score

❖ The biopsy findings correlate with cancer aggressiveness and predict

the T stage.

1. Gleason score (Grade Group)

2. The number of cores +ve cancer

3. The percentage of core involvement

4. Perineural space invasion

5. Lymphovascular invasion

6. Ductal, neuroendocrine differentiation

 MULTI-PARAMETRIC MRI

• The Prostate Imaging Reporting and Data System (PIRAD) score

• Indicated for persistent high PSA

• Extraprostatic extension : suboptimal sensitivity

• Seminal Vesicle invasion: high sensitivity

• Used to estimate risk of prostate cancer .

Pathology
 PROSTATIC INTRAEPITHELIAL NEOPLASIA

• Prostatic intraepithelial neoplasia (PIN) consists of architecturally benign prostatic acini or ducts lined by cytologically
atypical cells

• Is classified as low-grade and high-grade neoplasias

• The distinction between low-grade and high-grade PIN is based on the prominence of the nucleoli.

• Low-grade PIN should not be commented on in diagnostic reports.

• PIN by itself does not give rise to elevated serum PSA values
 PROSTATIC INTRAEPITHELIAL NEOPLASIA

• LGPIN and focal HGPIN do not increase risk of prostate cancer .

• Multifocal HGPIN : is precursor of prostate cancer . (risk of cancer 20 – 30 % )

• Incidence of HGPIN is 5% of prostate biopsies .

• Management :

Low grade PIN and focal HGPIN : monitor PSA + DRE , repeated biopsy if indicated

Multifocal HGPIN (>3sites) : monitor PSA + DRE + repeat biopsy 1-3 years
 Intraductal carcinoma of prostate (IDC-P)

• Has architectural of cytologic atypia that exceeds HGPIN .

• Frequently associated with high grade and poor prognostic cancer

• High grade pre-invasive lesion and high risk for developing high grade cancer .

• Recommended to be treated by definitive management ( Radical prostatectomy )

 SUBTYPES OF PROSTATE ADENOCARCINOMA

❖ Mucinous adenocarcinoma :
One of the least common morphologic variants of prostatic carcinoma.
It has a propensity to develop bone metastases and increased serum acid phosphatase and PSA levels with advanced disease.
Mucinous adenocarcinoma of the prostate treated by radical prostatectomy is not more aggressive than nonmucinous prostate
cancer

❖ Small cell carcinomas of the prostate

The average survival of patients with small cell carcinoma of the prostate is less than a year.

❖ Duct adenocarcinomas :
Arise in the large primary periurethral prostatic ducts, they may grow as an exophytic lesion into the urethra.
Most commonly in and around the verumontanum, and give rise to either obstructive symptoms or hematuria.
Most prostatic duct adenocarcinomas are advanced stage at presentation and have an aggressive course.
 Adenocarcinoma

• Most common type of prostate cancer .

• Arise from prostate gland epithelial cell
• Acinar adenocarcinoma : (>95% )
• Prostatic duct adenocarcinoma : rare aggressive , in periphral zone , tends to grow into urethra , presented by obstructive LUTS
+ hematuria , normal DRE , high risk to mestasize , treated as acinar .
• Non- adenocarcinoma : (<5%)
Transitional cell carcinoma
Small cell carcinoma
Sarcoma
 ADENOCARCINOMA

❖ Location :
The major tumor mass is peripheral in location.
The remaining cases, predominantly located in the transition zone.
Adenocarcinoma of the prostate is multifocal in more than 85% of cases

❖ Spread of Tumor :
The most frequent sites of metastatic prostate carcinoma are lymph node and bone.

❖ Grade
Although numerous grading systems exist for the evaluation of prostatic adenocarcinoma, the Gleason grading system is the most
widely accepted.
 Other types of Prostate cancer

❖ Urothelial Cell Carcinoma :-

• Primary urothelial cell carcinoma of the prostate without bladder involvement accounts for 1% to 4% of all prostate
carcinomas.
• stromal invasion is almost always identified.
• Primary urothelial cell carcinomas infiltrate the bladder neck and the surrounding soft tissue such that more than 50% of the
patients present with stage T3 or T4 tumors.

❖ Mesenchymal Tumors :-
• Sarcomas of the prostate account for 0.1% to 0.2% of all malignant prostatic tumors.
• Rhabdomyosarcoma is the most frequent mesenchymal tumor within the prostate and is seen almost exclusively in childhood.
• Leiomyosarcomas are the most common sarcomas involving the prostate in adults.
 GLEASON SCORE AND GRADE

• X+Y

• X: Most common grade

• Y: Second most common grade

 STAGING
CLINICAL VS PATHOLOGICAL

Partin Tables
Clinical staging Kattan Disease Burden and
Pathological staging
nomograms Prognosis (outcomes)
(pretreatment)

Kattan Nomograms
 NOMOGRAMS

• Several nomograms and tables were developed to:

• Predict the risk of PCa if biopsy is done based on the demographic data, Family history, DRE and PSA

• Predict the Pathological stage based on the clinical stage

• PCa progression, recurrence-free and survival

PROSTATE CANCER PREVENTION TRIAL (PCPT) RISK CALCULATOR
PREDICTION OF THE OF RISK OF PROSTATE CANCER IF A PROSTATE BIOPSY IS PERFORMED
 PARTIN TABLES
PREDICTION OF PATHOLOGICAL
STAGE AND LYMPH NODE
INVOLVEMENT
 BRIGANTI NOMOGRAM
THE PROBABILITY OF LYMPH NODE INVASION (LNI) FOR PATIENTS DIAGNOSED WITH MRI-
TARGETED AND SYSTEMATIC BIOPSIES
 SCREENING VS DIAGNOSIS

• Screening refers to testing for disease

in healthy, asymptomatic populations.

• Diagnosis is the identification of

disease symptomatic individuals

• The principal goal of screening is to

improve overall health outcomes by
identifying and treating disease at an
earlier stage.

• Shared-decision making:

• Risk VS Benefit

• false +ve

• over-treatment and diagnosis

 SYMPTOMS

• Most of the prostate Cancer patients are asymptomatic

• However, they may present with

• OBSTRUCTIVE LUTS

• HEMATURIA

• HEMATOSPERMIA

• Bone pain or pathologic fractures with or without Spinal cord compression (rarely a presenting symptom)
HOW TO APPROACH PCA

❖ General Role for Uro-oncology Topics:

1. Tissue diagnosis

2. Staging

3. Risk stratification

4. Management
DIAGNOSIS AND
STAGING
 STAGING
CLINICAL VS PATHOLOGICAL

• Clinical staging: is the assessment of disease extent using pretreatment parameters

• DRE, PSA values, needle biopsy findings, and radiologic imaging

• Pathologic stage: is determined after prostate removal and involves:

• Histologic analysis of the prostate, seminal vesicles +/- pelvic lymph nodes

• Estimates disease burden and is more useful than clinical staging for outcome prediction
 STAGING
CLINICAL VS PATHOLOGICAL

• Biochemical recurrence-free survival and cancer-specific survival are both inversely related to the pathologic stage

• The most important pathologic criteria that predict prognosis after radical prostatectomy are:

• Tumor grade

• Surgical margin status

• Extracapsular disease (ECE)

• Seminal vesicle invasion (SVI),

• Pelvic lymph node involvement ( presacral nodes , Common iliac nodes , external iliac nodes , obturator nodes , internal iliac
nodes )
 STAGING
CLINICAL VS PATHOLOGICAL
 DIAGNOSTIC MODALITIES
DRE

• The value of DRE for screening at PSA levels below 3.0 ng/mL is limited (PPV 4% -11%) however in those with PSA 3-10, the
PPV improved (33% - 83%)

• When DRE and PSA tests are used together in prostate cancer screening, detection rates are higher than either tests alone

• DRE is used to determine whether a lesion is palpable and is associated with local disease extent (clinical T stage).

• An abnormal DRE was associated with an increased risk for detecting high-grade (Gleason 8 to 10) prostate cancer in a
screened population

• PVV : Positive predictive value

ROLE OF IMAGING
DONEC QUIS NUNC

• Intermediate/high/
very high
RISK STRATIFICATION
 RISK STRATIFICATIONS

• Risk stratification were developed to:

• To assess the severity and prognosis (risk of progression and mortality)

• To choose the best management strategy with known benefit and risk
 D’AMICO RISK STRATIFICATION

• Established in 1998 (both studies evaluated the biochemical outcomes after RB and EBRT in clinically localized PCa)

• The proposed risk stratification revealed a significant 10 years Cancer-free survival as the following:

• low-risk: 83%

• intermediate-risk: 46%

• high-risk disease: 29%

 AUA RISK STRATIFICATION
VERY LOW & LOW RISK

• low-risk group was subcategorized into very low- and low-risk based on criteria analogous to that first proposed by Epstein.
 AUA RISK STRATIFICATION
FAVORABLE AND UNFAVORABLE INTERMEDIATE-RISK GROUP

• The Panel incorporated contemporary Grade Group categorizations to subcategorize intermediate-risk group into “favorable”
(Gleason 3+4, Grade Group 2) and “unfavorable” (Gleason 4+3, Grade Group 3) categories to facilitate decision-making
 RISK STRATIFICATION
AUA VS NCCN

• The Panel for the AUA guidelines did not substratify high-risk patients into high-risk and very high-risk (as has been proposed
by the NCCN).

• The rationale:

• is the lack of clinical utility as a context for decisions about treatment options is generally similar between high-risk and
very high-risk groups

• although there is differences in the outcome and prognosis in each group

NCCN AND AUA RISK STRATIFICATION

• ,
 GUIDELINE STATEMENTS (TOTAL = 68 STATEMENTS)

III.Recommended Approaches and Detail Specific Care Options

I.Shared Decision Making (5 Statements)
I.Active Surveillance (6 Statements)
II.Care Options by Cancer Severity/Risk Group
II.Prostatectomy (8 Statements)
I.Very Low-/Low-Risk (9 Statements)
III.Radiotherapy (8 Statements)
II.Intermediate-Risk (7 Statements)
IV.Whole Gland Cryosurgery (7 Statements)

III.High-Risk (6 Statements) V.HIFU and Focal Therapy (4 Statements)

IV.Outcome Expectations and Management (8 Statements)

VERY LOW & LOW RISK
 AUA GUIDELINES

• Staging in Asymptomatic Very Low-/Low-Risk Patients

• Clinicians should not perform abdomino-pelvic CT or routine bone scans (Strong Recommendation; Evidence Level C)
CARE OPTION FOR THE LOW AND VERY LOW RISK
NCCN VERY LOW RISK
NCCN LOW RISK
INTERMEDIATE RISK
 AUA GUIDELINES

• Staging in Intermediate-Risk Patients

• Clinicians should consider staging unfavorable intermediate-risk localized prostate cancer patients with cross sectional
imaging (CT or MRI) and bone scan (Expert Opinion)
CARE OPTION FOR THE INTERMEDIATE RISK
NCCN FAVORABLE INTERMEDIATE RISK GROUP
NCCN UNFAVORABLE INTERMEDIATE RISK GROUP
HIGH RISK GROUP
 AUA GUIDELINES

• Staging High-Risk Patients:

• Clinicians should stage high-risk localized prostate cancer patients with cross sectional imaging (CT or MRI) and bone scan
(Clinical Principle)

• Standard Treatment Option:

• Clinicians should recommend radical prostatectomy or radiotherapy plus ADT as standard treatment options for patients with
high-risk localized prostate cancer ( Strong Recommendation, Evidence Level A)

• Alternative Options :

• Clinicians should NOT RECOMMEND active surveillance.

• Watchful waiting should only be considered in asymptomatic men with limited life expectancy (≤5 years) (Moderate
Recommendation; Evidence Level C)
NCCN HIGH OR VERY HIGH RISK GROUP
MANAGEMENT
OPTIONS
 SHARED DECISION MAKING (SDM)
AUA GUIDELINES

• Counseling of patients to select a management strategy for localized prostate cancer should incorporate shared decision
making and explicitly consider cancer severity (risk category), patient values and preferences, life expectancy, pre-
treatment general functional and genitourinary symptoms, expected post-treatment functional status, and potential
for salvage treatment. (Strong Recommendation; Evidence Level: Grade A)

• Clinicians should encourage patients to meet with different prostate cancer care specialists (e.g., urology and either
radiation oncology or medical oncology or both), when possible to promote informed decision making. (Moderate
Recommendation; Evidence Level: Grade B)

• Effective shared decision making in prostate cancer care requires clinicians to inform patients about immediate and long-term
morbidity or side effects of proposed treatment or care options. (Clinical Principle)
AUA GUIDELINES
INTERMEDIATE RISK
NCCN GUIDELINES
HIGH AND VERY HIGH RISK
NCCN GUIDELINES
OBSERVATION (WATCHFUL WAITING)
VS
ACTIVE SURVEILLANCE
OBSERVATION (WATCHFUL WAITING) VS ACTIVE SURVEILLANCE

• Watchfull waiting : Refers to monitoring the patient until he develops metastases that require
palliative treatment

• Active surveillance: Allows delayed primary treatment , if there is biochemical or histological

evidence of cancer progression

• AVOID OR TO DELAY TREATMENT THAT MIGHT NOT BE IMMEDIATELY NECESSARY.

OBSERVATION (WATCHFUL WAITING) VS ACTIVE SURVEILLANCE
 OBSERVATION (WATCHFUL WAITING) VS ACTIVE SURVEILLANCE

❖ Advantages of active surveillance:

❖ Advantages of observation:
1. 66% of patients will avoid treatment:
• Avoidance of side effect of unnecessary definitive therapy
2. avoid side effects of definitive therapy that may be
and early initiation and/or continuous ADT
unnecessary

❖ Disadvantages of observation: 3. less impact on the quality of life

• Risk of urinary retention or pathologic fracture without 4. Reduce risk of overtreating indolent cancer
prior symptoms or concerning PSA levels
❖ Disadvantages of active surveillance:

• Periodic follow-up mpMRI and prostate biopsies may be

necessary.
 ACTIVE SURVEILLANCE

• Candidates : very-low-risk with life expectance >20 year OR low-risk with life expectance >10 years

• Avoid or Delay the costs ( functional, monetary) of treatment without compromising cancer cure

• Patients with favorable intermediate-risk prostate cancer may be considered for active surveillance, with risk of Ca
progression

• Cancer progression may have occurred if:

1. Gleason Grade 4 or 5 cancer is found upon repeat prostate biopsy

2. increase # of cores or % of core from previous biopsy

• Evidence of PCa progression will prompt conversion to potentially curative treatment in active surveillance patients
 ACTIVE SURVEILLANCE PROTOCOL
NCCN GUIDELINES

• PSA every 6 months

• DRE every 12 months

• Repeat prostate biopsy every 12 months :

• Earlier if abnormal prostate exam, MRI or PSA increases (unless life expectancy is less than 10 yr)

• Should be repeated within 6 months of diagnosis if initial biopsy was <10 cores or assessment discordant (eg, palpable tumor
contralateral to side of positive biopsy)

• MRI-US fusion biopsy may improve the detection of higher grade (grade group 2 and above)

• Repeat mpMRI every 12 month

 WATCHFUL WAITING (OBSERVATION)

• Monitoring continues until symptoms develop or are imminent (ie, PSA >100 ng/mL) who will then begin palliative therapy

• Candidates: preferred for men with:

• low or intermediate-risk prostate cancer with life expectancy <10 y

• high risk <5y life expectancy

ABLATIVE THERAPY
 ABLATIVE THERAPY
AUA GUIDELINES

• Clinicians should inform low-risk prostate cancer patients considering whole gland cryosurgery that consequent side effects are
considerable and survival benefit has not been shown in comparison to active surveillance. (Conditional
Recommendation; Evidence Level: Grade C)

• In select patients with intermediate-risk localized prostate cancer, clinicians may consider other treatment options such as
cryosurgery. (Conditional Recommendation; Evidence Level: Grade C)

• Clinicians should inform low-risk and intermediate-risk prostate cancer patients who are considering focal therapy or high
intensity focused ultrasound (HIFU) that these interventions are not standard care options because comparative outcome
evidence is lacking. (Expert Opinion)

• Cryosurgery, focal therapy and HIFU treatments are not recommended for men with high-risk localized prostate cancer
outside of a clinical trial. (Expert Opinion)
 ABLATIVE THERAPY
PARTIAL (FOCAL) & WHOLE GLAND

• Criteria for selection of men for focal ablation:

• Controversial and vary widely according to institution.

• But typically unifocal, or limited focality, cancer with concordance of both imaging and biopsy.

• Careful counseling regarding:

• Not the standard

• risks and benefits is required

• with a clear understanding regarding the investigational nature of the approach (absence of long-term clinical follow-up).

• need for re-treatment —> the risk of worsened outcomes if for salvage therapy
 CRYOSURGERY
(CRYOTHERAPY OR CRYOABLATION)

• Induces tumor tissue damages through local freezing.

• In low-risk disease when cryotherapy US used in the initial disease setting, the
reported 5-year biochemical disease-free rate 65% to 92%

• A study involved 244 men with T2 or T3 disease

• cryotherapy +neoadjuvant ADT VS EBRT + neoadjuvant ADT.

• There was no difference in 3-year OS or DFS.

• Patients who received cryotherapy reported poorer sexual function

 CRYOSURGERY AS A SALVAGE TREATMENT POST EBRT

• Salvage focal (SFC) cryoablation VS salvage total (STC) cryoablation

• The median follow‐up was 31 and 53 months (P = 0.004) for SFC and STC, respectively.

• The 5‐year Biochemical Failure‐free survival rates was higher in the salvage focal cryotherapy

• ED and Urinary incontinence was higher in the STC group ; and recto‐urethral fistula was reported also in the STC
group (4%) of patients
 HIGH INTENSITY FOCUSED ULTRASOUND (HIFU)

• Induces tumor tissue damages through Heating

• HIFU has been studied for treatment of radiation recurrence

• The median biochemical recurrence-free survival at 63 months

• 5-year OS of 88%

• Cancer-specific survival of 94%.

RADICAL PROSTATECTOMY
VS
RADIATION THERAPY
 RADICAL PROSTATECTOMY VS RADIATION THERAPY
• Both have comparable oncologic outcomes at 10 years of follow-up

• Much of the counseling relates to relative risks and toxicities (urinary and sexual).

• RP: Noticeable early worsening of urinary and sexual • RT: minimal urinary and sexual dysfunction in the short-term,
function. however there is an incremental decline overtime

• Delayed secondary malignancies: controversial, but several

• Patients should be counseled for incontinence and
studies support an increased risk of rectal and bladder
impotence in the with probability for recovery, along with
malignancy
a therapeutic plan pre and post Sx

• If intermediate or high risk, needs concomitant ADT—> the

• Men with baseline LUTS may benefit from surgery
early toxicity after radiation may be primarily driven by this.
despite the early deterioration in urinary function
 RADICAL PROSTATECTOMY

• Surgery is deferred for 6-8 weeks after needle biopsy of the prostate and 12 weeks after transurethral resection of the prostate.

• Three goals of the surgeon (in order of importance) cancer control, preservation of urinary control, and preservation of sexual
function.

• Surgical technique to preserve/achieve earlier recovery of sexual function:

• High anterior release of the NVBs at the apex before division of the dorsal vein

• Preserve both NVBs (or at least one of them)

• Preop potency is still the most important variable

• NVB should be excised if:

• Induration is palpable in the lateral pelvic fascia

• the bundle is fixed to the prostate

 INDICATIONS FOR ADJUVANT EBRT

• High/Very high :

• - ve LN

• One of the adverse features post RP:

• EPE

• SV

• +ve surgical margin

 INDICATIONS FOR ADJUVANT ADT

• High/Very high with +ve LN

 CONCLUSION

• In general, the decision between surgery and radiation, for most men with localized prostate cancer, is dependent upon
patient perception and preference, and a decision regarding which anticipated side effects seem most tolerable to the
individual.

• Active surveillance is the preferred form of treatment for men with very low, low - risk and selected patients with favorable
intermediate - risk disease

• RP and EBRT are best preserved for intermediate, high and very high risk patients
 References
• Campbell 12th Edition

• AUA Guidelines

• NCCN Guidelines

• EAU Guidelines
THANK YOU