Prostate cancer

- Committee

• Chair of the Oncology Committee of Egyptian health council Guidelines: Prof  Hussein Khaled.

• The Oncology Committee Members: Ebtesam Saad Eldin , Ihab Khalil, Emad Hamada, Fouad Abuotaleb,  Hesham Elghazaly, Hesham Tawfik, , Khaled Abdelkarim, Lobna ezz Elarab, Mary Gamal, Mohamed Abdel Mooti,  Mohamed Gamil, Nervana Hussein, Ola Khorshid, Omar Sherif Omar, Rasha shaltout, Rasha fahmy , Samir Shehata,  Yousri Wasef & Yousri Rostom.

• Chair of the prostate cancer Scientific Committee: Emad Hamada 

• The prostate cancer Scientific Group Members: Alaa Meshref , Ehab Khalil , Hatem abu elkassem , Hesham Tawfik , Hussien Khaled , ,Mary Gamal , Nervana hussein .

- Abbreviations

ADT ( Androgen deprivation therapy )

ART (Adjuvant RT)

AS (Active Surveillance)

AUA (American Urological Association)

BRCA1/2 (Breast Cancer Gene)

BT  (Brachytherapy)

CBC & differential ( complete blood count & differential)

CT ( computed tomography )

CRPC ( castrate resistant prostate cancer )

DRE ( digital rectal examination )

DT ( doubling time )

dMMR ( deficient mismatch repair )

EAU ( European Association Of Urology )

EBRT ( external beam radiotherapy )

ECOG ( eastern cooperative oncology group )

ESMO ( European Society For Medical Oncology )

HSPC ( hormone sensitive prostate cancer )

HRR ( homologous recombination repair )

HRD (Homologous recombination deficiency)

H-MSI ( high levels of microsatellite instability )

IHD ( ischemic heart disease )

IRF ( intermediate risk factors )

IMRT ( intensity modulated radiation therapy )

IGRT (Image Guided RT)

KFT ( Kidney function test )

LFT ( liver function test )

LHRH ( luteinizing hormone releasing hormone )

LN ( lymph node )

MCRPC ( metastatic castrate resistant prostate cancer )

MDT ( multi disciplinary team )

MHSPC ( metastatic hormone sensitive prostate cancer )

MRI ( magnetic resonance imaging )

MRI-Bx (MRI guided biopsy)

Mp MRI ( multiparametric MRI )

NCCN ( National Comprehensive Cancer Network )

NMCRPC ( non metastatic castrate resistant prostate cancer )

PARP-inhibitors: poly (ADP-ribose) polymerase Inhibitors

Pca (Prostate Cancer)

PET ( positron emission tomography)

PIRADs (Prostate Imaging-Reporting and Data System)

PS ( performance status )

PSA ( prostatic specific antigen )

PSA DT ( PSA doubling time )

PSMA ( prostate specific membrane antigen )

PLND ( pelvic lymph node dissection )

RP ( radical prostatectomy )

RT (radiation therapy)

SBRT ( stereotactic body radiotherapy )

S-RT (Salvage RT)

TRUS ( transrectal ultrasound )

TRUS-Bx (transrectal guided ultrasound biopsy)

TURP ( trans urethral resection of the prostate )

VMAT (Volumetric Modulated Arc Therapy)

- Glossary

Localized prostate cancer

Prostate cancer that has not spread beyond the prostate

Locally Advanced prostate cancer

Patients with T3b or T4 disease on their initial evaluation based upon the presence of presumed extra-prostatic extension and/or seminal vesicle involvement, or invasion of adjacent organs and/or regional LN metastases by radiological investigations

Biochemical recurrence

A rise in serum PSA and not accompanied by signs, symptoms, or radiographic evidence of locally recurrent or disseminated disease. (by conventional Imaging and/or PSMA-PET)

A)  PSA persistence/recurrence after RP

Failure of PSA to fall to undetectable levels (PSA persistence) or undetectable PSA after RP with a subsequent detectable PSA that increases on 2 or more determinations (PSA recurrence) or that increases to PSA >0.1 ng/mL.

B) Biochemical recurrence after EBRT with or without hormonal therapy is defined as a PSA rise by 2 ng/mL or more above the nadir PSA

Metastatic Hormone Sensitive Prostate Cancer (MHSPC)

MHSPC is diagnosed when cancer has spread beyond the prostate to the body and serum testosterone levels are typically >50 ng/dL ,Treatment is often effective with low testosterone levels .

MHSPC High volume criteria ( CHAARTED trial )

Presence of visceral metastases

and/or ≥4 bone metastases, including at least one beyond the vertebral bodies and pelvis

MHSPC low volume criteria are defined as those who do not meet the high volume criteria

MHSPC High risk criteria ( LATITUDE trial )

 At least two of :

 a-Gleason score of ≥ 8

b-Bone metastasis of ≥ 3

 c-Presence of Visceral metastasis

MHSPC low risk  criteria are defined as those who do not meet the high risk  criteria

Non metastatic CRPC

Males who are diagnosed with CRPC at a time when the only manifestation of progressive disease is an increase in serum PSA level, without demonstrable radiographic disease progression (on bone scan and conventional CT) or by PSMA-PET  involving specific organs, , with PSA DT ≤10 months, and a serum PSA ≥2 ng/mL.

Metastatic CRPC 

Metastatic castration-resistant prostate cancer (CRPC) is advanced prostate cancer with evidence of disease progression and spread to other parts of the body despite castrate levels of serum testosterone (<50 ng/dL) after medical or surgical orchiectomy.

- Executive Summary

This guidance provides a data-supported approach to the diagnosis, risk stratification, treatment and follow up of patients diagnosed with prostate cancer

- Introduction

Prostate cancer is the fourth most common cancer in Egypt , with estimated number of new cases per year about 5181 ( 7%) ( 1 )

Organ confined disease , locoregional metastasis , Distant metastasis are presented in 80 %  , 15% , 5% of cases with a 5 year overall survival 90-99% , 60-80%, 30-40% respectively ( 2 )

➡️Scope of the Guidelines

These guidelines are developed to improve the quality of care for prostate cancer patients Via providing a uniform standard of care across the country to help in early diagnosis , risk stratification and treatment  for prostate cancer  , with less aggressive treatment options and improved clinical outcomes. These guidelines cover primary diagnosis, staging, treatment and follow-up of prostate cancer patients.

➡️Target audience

 Clinicians who are involved in the care and treatment of patients with prostate cancer, including medical oncologists, radiation oncologists, clinical oncologist, urologists , surgeons, interventional radiologists, radiologists, pathologists, and palliative care specialists.

- Methodology

▪️ A comprehensive search for guidelines was undertaken to identify the most

relevant guidelines to consider for adaptation.

▪️ inclusion/exclusion criteria followed in the search and retrieval of

guidelines to be adapted:

▪️ All retrieved Guidelines were screened and appraised using AGREE II

instrument (www.agreetrust.org) by at least two members. the panel decided

a cut-off point or rank the guidelines (any guideline scoring above 50% on

the rigour dimension was retained)

The NCCN , ESMO , AUA , EAU guidelines are the main sources used while formulating the national guidelines for prostate cancer .

➡️Evidence assessment

According to WHO handbook for Guidelines we used the GRADE (Grading

of Recommendations, Assessment, Development and Evaluation) approach

to assess the quality of a body of evidence, develop and report

recommendations. GRADE methods are used by WHO because these

represent internationally agreed standards for making transparent

recommendations. Detailed information on GRADE is available through the

on the following sites:

▪️ Table 1: Quality of evidence in GRADE

➡️The strength of the recommendation

- Recommendations

1- Screening for prostate cancer

Early PSA testing (baseline PSA followed by risk-adapted follow-up) can be offered to men >50 years, men >45 years with a positive family history of prostate cancer, and BRCA1/2 carriers >40 years

Conditional recommendation , moderate quality level of evidence (Randomized Study ) 3

2- Work up for newly diagnosed prostate cancer

➡️History and physical examination

 Personal and family history, Physical examination, DRE , Assessment of ECOG performance status should be done

Strong recommendation, high quality level of evidence (prostate cancer prevention trial ) 4

Assessment of life expectancy is a very essential tool in the plan of management of prostate cancer , Life expectancy should  be estimated using: The WHO’s Life Tables by country

Strong recommendation, moderate quality level of evidence ( Global Health Observatory data repository) 5

➡️Laboratory Studies

Base line tumor marker:  serum PSA (Total, Free ) is  the recommended  initial laboratory studies for localized  prostate cancer

Strong recommendation, high quality level of evidence  ( Systematic Review , comparative study ) 6,7

➡️Radiological Studies

TRUS is  the initial imaging studies for diagnosis of  prostate cancer,

Strong recommendation, high quality level of evidence  (Systematic Review ) 6

MRI prostate or mpMRI ( if available ) is to be used in the staging and characterization of prostate cancer

Conditional recommendation, high quality evidence ( prospective study , Meta analysis ) 8,9

Radiologists should utilize PI-RADS V 2.1 in the reporting of multi-parametric MRI (mpMRI) imaging

 Strong  Recommendation,  High quality Evidence Level ( Systematic Review ) 6

Standard MRI techniques should be used for examination of the pelvis and/or abdomen for initial evaluation of intermediate and high / very high risk patients and for planning purposes in radiotherapy protocols

Strong  Recommendation , high quality Evidence Level  (Diagnostic meta analysis)  9

Bone imaging is indicated in the initial evaluation of intermediate and high / very high risk patients to exclude skeletal metastasis

Strong recommendation, high quality evidence(retrospective analysis ) 10

PSMA-PET if available to be considered as an alternative to standard imaging of bone and soft tissue in high and very high risk patients .

Conditional  recommendation, high quality evidence(retrospective analysis )11

➡️Initial Biopsy 

Definitive diagnosis of cancer prostate requires 6-12 core biopsies of the prostate, using a needle under transrectal / transperineal ultrasound TRUS guidance.

Strong  Recommendation; high  quality Evidence Level (confirmatory study , prospective Comparative analysis ) 12, 13

For biopsy-naïve patients who have a suspicious lesion on MRI, clinicians can perform targeted biopsies of the suspicious lesion either cognitive or software guided 

Conditional  Recommendation , high quality Evidence Level ( prospective multicenter study , Comparative study  ) 14 , 15

3- Risk stratification and Management of Localized / Locally advanced prostate cancer

Patients with localized prostate cancer should be classified into very low , low , intermediate ( Favourable and unfavourable)  , high and very high risk groups

Strong  Recommendation , high quality Evidence Level (  Retrospective analysis  ) 16

Risk stratification of clinically localized prostate cancer facilitate care decisions and guide clinicians in the implementation of selected management options..

Strong  Recommendation , high quality Evidence Level (Systematic Review) 17

Patients with prostate cancer should be managed through a multidisciplinary team ( Urologist , medical Oncologist , Radiation oncologist , Radiologist , and Pathologist )

Strong  Recommendation , high quality Evidence Level ( Retrospective review  ) , 18

It is Recommended to use  one of the following options in the management of very low/low risk groups (according to MDT decision and patient preference):

If expected patient survival ≥ 10  years,:

Strong  Recommendation , high quality Evidence Level ( Population based validation ) 19

In asymptomatic patients with prostate cancer and limited life expectancy , watchful waiting is recommended

  Strong Recommendation, high quality Evidence Level ( Systematic review ) ,17

According to MDT decision and patient preference; It is recommended to use  one of the following options in the management of favourable intermediate risk groups ( Life expectancy ≥ 10  years):

Strong Recommendation,  high quality Evidence Level , ( Systematic review  , Retrospective analysis ) 17, 20 

It is recommended to use  one of the following options in the management of favourable intermediate risk prostate cancer  (Expected Survival 5-10 Years ):

Strong  Recommendation , high quality Evidence Level (retrospective analysis)  20

Brachytherapy monotherapy  is a recommended  option for patients with very low, low, or favorable intermediate-risk prostate cancer and life expectancy > 10 years  with acceptable 10-year recurrence-free survival rate for LDR/HDR brachytherapy

Strong  Recommendation , high quality Evidence , ( Literature review ), 21

RP + PLND  or EBRT + short course ADT ( 6 months ) are the recommended  options for management of unfavourable intermediate risk patients.

Strong  Recommendation , high quality Evidence Level ): ( Systematic review   , retrospective analysis  )17 ,  20

Long term ADT ( 2- 3 years ) combined with EBRT is the recommended  primary treatment for  high risk or very high risk prostate cancer patients  

Strong  Recommendation , high quality Evidence Level ( Randomized trial ) 22 

RP and PLND is a valid option in very selected cases with high or very high risk prostate cancer based on MDT discussion

Conditional recommendation , high quality level  (  Retrospective analysis ) 23

➡️Locally advanced prostate cancer

Neoadjuvant ADT ( 4-6 months ) followed by ADT + EBRT , then ADT for 2 years  is the recommended treatment option for patients with locally advanced prostate cancer 

Strong recommendation , high quality level  ( Randomized trial ) 24

RP and PLND  can be an option in selected cases  of locally advanced prostate cancer according to MDT decision

Conditional recommendation , high quality level  (  Retrospective analysis ) 23

Patients who choose active surveillance program should have regular follow-up with baseline biopsy ,  serum PSA level  , Prostatic MRI  and key principles of active surveillance  include:

 PSA every 3months unless there is an earlier clinical indication

DRE  every 6 months unless there is an earlier clinical indication.

Radiological examination +/- Prostatic biopsy if there is a clinical indication

Conditional  recommendation, moderate quality evidence  ( systematic review ), 25

Watchful waiting  involves monitoring with a history and physical exam every 12 months (without surveillance biopsies) until symptoms develop.

Strong recommendation, high quality evidence  ( prospective study , cancer epidemiology study ) 26, 27

➡️Radical prostatectomy

RP +/- PLND is the recommended therapy for any patient with clinically localized prostate cancer that can be completely excised surgically, Life expectancy of ≥10 years, and  has no serious comorbid conditions that would contraindicate an elective operation

Strong recommendation, high quality evidence  (retrospective analysis ), 28

Extended PLND is recommended when PLND is performed as it provides more complete staging and may cure some patients with microscopic metastases . An extended PLND includes removal of all node-bearing tissue from an area bound by the external iliac vein anteriorly, the pelvic sidewall laterally, the bladder wall medially, the floor of the pelvis posteriorly, Cooper's ligament distally, and the internal iliac artery proximally.

Strong recommendation, high quality evidence  (systematic review ), 29

Robotic surgery could be done (if available ) in selected university hospitals after gaining sufficient learning curve

Conditional recommendation , high quality evidence ( retrospective analysis )30

➡️Radiotherapy

Indications of Post-prostatectomy ART include Adverse pathologic features : Positive margins, Seminal vesicle invasion and  Extracapsular extension or persistent PSA levels (PSA does not fall to undetectable levels).

Strong recommendation, high quality evidence  ( randomized clinical trial ), 31

Radiotherapy is one of the recommended modalities of radical therapy for localized prostate cancer patients without severe complications where the results of definitive radiotherapy are comparable to radical prostatectomy for patients with similar recurrence risk. Prospective analysis

Strong recommendation, high quality evidence  ( Prospective analysis  ), 32

Radiotherapy in prostate cancer is recommended to be in the treatment plan through expert MDT and should be carried out in a well-equipped centres with trained personnel and adopting advanced EBRT techniques that include:  IMRT, VMAT , image-guided (IGRT) and SBRT facilities.

➡️Good statement practice

Short-term precise hypo-fractionated radiotherapy can be used as it shortens the treatment course significantly while the treatment results are equivalent to those of conventional high-dose radiotherapy.

Conditional recommendation, high quality evidence  ( Systematic review, single institution experience ), 33, 34

Addition of a focal boost to the intra-prostatic lesion can be used as it improved disease free survival  for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life.

Conditional recommendation , high quality evidence ( randomized trial ), 35

Prophylactic nodal radiation should be considered in locally advanced prostate cancer and clinically positive nodes , it should be dose escalated in the presence of positive nodes by imaging procedures.

Strong recommendation, high quality evidence, ( Randomized trial ) , 36

➡️Androgen deprivation therapy

ADT includes LHRH agonist as Goserline or leuprolide , first  generation antiandrogen (Bicalutamide) should be given  at least  7 days  before LHRH agonist only to avoid flare up phenomenon .

Strong recommendation, high quality evidence  (population based cohort study ) , 37

We recommend against Combined androgen blockade (medical or surgical castration combined with an antiandrogen) as it provides modest to no benefit over castration alone in patients with prostate cancer

Strong recommendation, high quality evidence ( randomized  controlled trials ) ,38

ADT should not be used as monotherapy in clinically localized prostate cancer unless there is a contraindication to definitive local therapy, such as life expectancy less than 5 years and presence of comorbidities. Under those circumstances, ADT may be an acceptable alternative if the disease is high or very high risk

Conditional  recommendation, high quality evidence  (overview of randomized trials), 39

Follow Up

For patients initially treated with definitive therapy with intent to cure, PSA testing  should be done every 3 months for the first 2 years then every 6 months till 5 years and then annually.

Strong recommendation, moderate quality level of evidence (prostate cancer prevention trial ) 4

4-Management of biochemical recurrence

➡️Laboratory Studies

Serum PSA (Total, Free )  and  PSA doubling time ( PSA DT )  are the laboratory studies  for patients with biochemical recurrence

Strong  Recommendation , high quality Evidence ( Comparative study ), 7

➡️Radiological  Studies

Standard MRI techniques for examination of the pelvis and/or abdomen  is recommended as part of workup for recurrence or progression

Strong  Recommendation , high quality Evidence Level (Diagnostic meta analysis) 9

Bone imaging should be considered for the evaluation of the patient post-prostatectomy when there is failure of PSA to fall to undetectable levels, or when there is undetectable PSA after RP with a subsequent detectable PSA that increases on 2 or more subsequent determinations.

Strong recommendation, high quality evidence(retrospective analysis ) 10

Bone imaging should be considered for the evaluation of patients with an increasing PSA or positive DRE after RT

Strong recommendation, high quality evidence(retrospective analysis ) 10

In patients with a BCR after local therapy, prostate-specific membrane antigen (PSMA)-PET ( if available ) to be done in lieu of conventional imaging or after negative conventional imaging for further evaluation of clinical recurrence.

Conditional Recommendation, high quality level  ( Systematic Review ) , 17

➡️ Treatment of Biochemical Recurrence

Salvage RT in addition to Six months ADT ( concurrent / Adjuvant ) is recommended for patients with BCR following RP and with high-risk features :

( Gleason Grade Group 4 to 5, PSADT ≤ 6months, persistently detectable post-operative PSA, seminal vesicle involvement). 

Strong  Recommendation, high quality level ( randomized trial ) 40

Salvage radiation for a detectable prostate-specific antigen (PSA) after RP is more effective when given at lower levels of PSA.

Strong  Recommendation, high quality level ( Systematic Review ) , 17

Post-prostatectomy SRT is to treat prostate bed ± pelvic LN  , where PSA cut-off value for SRT (range: 0.2–0.5 ng/ml) and 0.2 ng/ml is the preferable value

Conditional recommendation, high quality evidence ( retrospective analysis ),41

Immediate rather than deferred ADT is recommended in men with biochemical recurrence after Radiotherapy is recommended  if there are high-risk features for early metastases, including a   clinical Gleason score 8 -10, or an interval to biochemical recurrence ≤18 months after definitive radiotherapy

Strong recommendation , high quality level  ( Randomized trial  ) 42

Salvage RP and PLND can be offered in selected cases with biochemical recurrence after Radiotherapy according to MDT decision

Conditional recommendation , high quality level  (  Retrospective analysis ) 23

 5- Management of

➡️History and physical examination

Including assessment of ECOG Performance status , Presence of peripheral neuropathy , History of seizures or cerebrovascular problems , History of cardiovascular disease and other comorbidities and  Risk of fall & fractures

Good practice statement

➡️Laboratory Studies

 CBC, KFT’s and LFT’s, Serum Testosterone Level , HbA1c,  serum PSA (Total, Free ) , PSA doubling time ( PSA DT )  , serum cholesterol /LDL & HDL & S triglycerides  are the recommended work up for metastatic prostate cancer

Good practice statement

➡️Imaging studies

Standard CT techniques should be used for examination of the chest , abdomen and pelvis as an initial  evaluation of advanced prostate cancer

Strong  Recommendation , high quality Evidence ( Diagnostic meta analysis) 9

Bone imaging should be considered for the evaluation of patients with advanced prostate cancer

Strong recommendation, high quality evidence(retrospective analysis ) 10

PSMA-PET if available to be considered as an alternative to standard imaging of bone and soft tissue in patients with advanced cancer prostate  .

Conditional  recommendation, high quality evidence(retrospective analysis )11

 Echocardiogram should be done to assess the cardiac condition as it can guide  further management

Good practice statement

➡️Pathological examination  

 Transrectal US Biopsy is recommended in cases with de novo metastatic prostate cancer

Strong recommendation, high quality level of evidence  (Systematic Review ) 6

In previously treated PC with previous biopsy , we recommend against  re-biopsy from the prostate in metastatic setting

Good practice statement

Biopsy from accessible metastatic lesions to identify patients with small  cell/neuroendocrine histomorphologic features can be done in patients with metastatic CRPC

Conditional recommendation , strong quality level ( prospective analysis ) 43

A)Metastatic hormone sensitive prostate cancer

Patients with low-volume metastatic HSPC should be considered for ADT and local radiotherapy to the prostate if not previously given

Strong recommendation , high quality level (  Randomized clinical trial ) 44

ADT plus docetaxel is the standard of care in treatment of patients with high-volume metastatic HSPC

Strong recommendation , high quality Evidence   (randomized clinical trial) ,45

ADT plus Apalutamide  or Enzalutamide is the standard of care in treatment of patients with high-volume metastatic HSPC who are not candidate for docetaxel

Strong recommendation , high quality Evidence  (Randomized clinical trials  ) 46,47,48

Radiation therapy to the prostate should NOT be performed in men with high-volume metastatic disease outside the context of a clinical trial unless for palliative intent

Good practice statement

B)Non Metastatic Castrate Resistant Prostate Cancer

Castrate levels of testosterone should be documented in patients with signs of progression, If serum testosterone levels are <50 ng/dL, the patient should undergo disease workup with bone and soft tissue imaging

Strong recommendation , high quality level ( Literature review ), 49

Apalutamide or enzalutamide should be considered for men with non metastatic  CRPC

Strong recommendation , high quality level ( Randomized clinical trials  ) 50, 51

C)Metastatic Castrate Resistant Prostate Cancer 

Abiraterone acetate plus prednisone + ADT is the standard of care in the management of patients with metastatic CRPC previously treated with Docetaxel

Strong recommendation , high quality level  ( Randomized clinical trial ) 52

Enzalutamide +ADT is the standard of care in the management of patients with metastatic CRPC previously treated with docetaxel and not candidate for Abiraterone acetate + prednisone

Strong recommendation , high quality level ( Randomized clinical trials ) 53,54

Docetaxel + ADT is the standard of care in the management of patients with metastatic CRPC not previously treated with Docetaxel

Strong recommendation , high quality level  (literature review ), 55

 Patients being treated for CRPC should  be closely monitored with radiologic imaging (CT, bone imaging), PSA tests, and clinical exams for evidence of progression.

Strong recommendation, high quality evidence(retrospective analysis ) 10

 Urgent MRI of the spine to detect cord compression is very strongly recommended in men with CRPC with vertebral metastases and neurological symptoms

Strong recommendation , high quality Evidence  (Systematic review ) ,56

6 - Special  considerations

Docetaxel should be avoided in patients with ECOG PS≥ 2, IHD, presence of comorbidities, grade III/IV peripheral neuropathy , Absolute neutrophil count < 1000/mm3

Strong recommendation , high quality level  ( randomized clinical trial ) 45

Apalutamide should be avoided in patients with recent cardiovascular disease or  hypothyroidism .

Strong recommendation , high quality Evidence ( randomized clinical trial ) 46

Enzalutamide should be avoided in seizure prone patients or with history of seizures 

Strong recommendation , high quality Evidence ( randomized clinical trial ) 47, 48

Abiraterone should be avoided in patients with uncontrolled diabetes , hepatic impairment , cardiovascular disease

Strong recommendation , high quality Evidence ( randomized clinical trial ) 52

Therapy should be continued until clinical progression or intolerable toxicity 

Strong recommendation , high quality Evidence (randomized clinical trials )45, 47, 48, 52

Palliative RT is recommended  for symptomatic control and prevention of complications from metastatic lesions as bone or brain .

Strong recommendation , high quality Evidence  (Systematic review ), 57

Bisphosphonate or denosumab is recommended In patients with bone metastases from CRPC at risk for clinically significant skeletal-related events (SREs)

Strong recommendation , high quality Evidence ( Randomized trial ),58

The use of a second AR inhibitor (abiraterone after enzalutamide  or vice versa) is not recommended

Strong recommendation , high quality level ( Randomized trial ) 59

Germline testing for BRCA2 and genes associated with cancer predisposition syndromes can be done in patients with positive family history of cancer .

Conditional recommendation , high quality Evidence  (comparative study ) 60

Tumor testing for homologous recombination genes and mismatch repair defects (or microsatellite instability) can be considered in patients with mCRPC

Conditional recommendation , high quality Evidence  (Randomized trial ) 61

Small cell/neuroendocrine carcinoma of the prostate should be considered in patients with disease that no longer responds to ADT and are positive for metastases. These relatively rare tumors are associated with low PSA levels despite large metastatic burden and visceral disease.

Strong recommendation , high quality Evidence ( Retrospective analysis ), 62

Etoposite / platinum is the standard of care in the management of small cell neuroendocrine tumors of the prostate

Strong recommendation , high quality Evidence  ( retrospective analysis  ), 63

Life style measures is recommended to maintain bone health are recommended for men on ADT: weight-bearing exercise, stop smoking , adequate calcium intake and vitamin D status

Strong recommendation , high quality Evidence  ( Retrospective analysis ), 64

 Clinical indicators for monitoring

For patients newly diagnosed with prostate cancer , Transrectal  U/S guided biopsy from prostate , Total/ free PSA , imaging studies should be done

For patients initially treated with definitive therapy with intent to cure, serum PSA levels should be measured.

 For patients who are on treatment , Regular PSA levels  and radiological assessment upon indication should be done

➡️Research Gaps

Head to Head Comparative study between different novel hormonal treatment  in the metastatic setting with overall survival ,  r PFS and  PFS 2 as endpoints together with the safety profile for each

Head to Head comparative study between Triplet and Doublet therapy in metastatic HSPC and nm CRPC in terms of OS , PFS , safety profile

➡️Update of this guideline

This guideline will be updated whenever there is new evidence.

- References

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2-   Rebello et al , Nature review 2022

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- Annexes

Table 1 : Risk stratification according to clinical /Pathologic features  

NCCN Clinical Practice Guidelines in Oncology for prostate cancer , version 4.2023

Table 2 : Definitions of active surveillance and watchful waiting 

EAU Recommendations

Table 3 : AJCC TNM staging system for prostate cancer

Table 4 : : Definition of Histologic Grade Group (G)

Recently, the Gleason system has been compressed into so-called Grade Groups.

Table 5 : Doses and fractionation of EBRT , Brachytherapy and combined

NCCN Clinical Practice Guidelines in Oncology for prostate cancer , version 4.2023