PROSTATE CANCER SCREENING

84 I KENYA NATIONAL CANCER SCREENING GUIDELINES

PROSTATE CANCER SCREENING

Introduction

Prostate Cancer burden

Prostate cancer is the fourth leading cancer in incidence globally, with higher mortality

reported in less developed regions than in more developed regions. Prostate cancer is

a disease of the aging male, the majority presenting after 65 years (average of 68 years).

This is the most common cancer among elderly male population all over the world, with

a slight preponderance in blacks. Incidentally autopsy prevalence rates of prostate can-

cer are the same across all races suggesting environmental factors play a crucial role in

aetiology. This compares well with.

In Kenya, prostate cancer is the commonest cancer in males with 2,864 new cases (14.9%) (GLOBOCAN, 2018). Currently, the proportion of men diagnosed with prostate cancer by age is as tabulated below:

Age of Men in Years Percentage proportion
A 55 10.1%
55-64 30.7%
65-74 35.3%
75- 4 19.9%
A 4 4.4%

Source: KNH Cancer Registry, 2018: Prostate cancer new cases %

by age

Studies have shown that compared with other countries, patients with prostate cancer in Kenya present at a similar mean age at diagnosis, but with more advanced disease and more aggressive tumours compared(Dickstein et al, 2009; Jonnson et al; Hemed et al, 2014).

RATIONALE FOR SCREENING

• There is no role for MASS screening for prostate cancer

• Screening for prostate cancer is a highly individualized decision between a client and his caregiver.

Text Box 1

Effects of Prostate Specific Antigen (PSA) screening

PSA screening has induced a significant downward migration in age and stage

(both cliniacal and pathologic) at diagnosis. It may also have a beneficial effect

on prostate cancer mortality. However, the absolute effect is small relative to

the number needed to screen and treat to cure a single individual. For every

1,000 men tested, approximately 100 to 120 will have an elevated PSA value

(Eastham et al, 2003).

Therefore, mass screening is not recommended.

These guidelines are meant to equip healthcare providers with information on early detection of prostate cancer for the purpose of reducing prostate cancer mortality. They should have a high index of suspicion and should be keen to screen patients presenting with the following lower urinary tract symptoms for prostate cancer:

o Frequency and nocturia

o Difficulty in starting or stopping the urine flow

o Inability to urinate

o Weak, decreased or interrupted urine stream

o A sense of incompletely emptying the bladder.

o Burning or pain during urination (dysuria)

o Post-micturition dribbling

o Urgency in urinating

o Blood in the urine or semen

PSA-Based Screening Guidelines

Various international organizations (listed in the references section) have issued guide-

lines on prostate cancer screening. These guidelines differ in their recommendations

regarding:

  Whether or not to provide routine PSA-based prostate cancer screening
  In what age groups and life expectancies

However, the guidelines agree that:

  PSA-based prostate cancer screening requires an informed, shared
decision-making process
  The decision should reflect the patient’s understanding of the possible
benefits and risks
  The decision should respect the patient’s preferences and values.

SHARED DECISION MAKING

A well-informed patient understands the ratio of benefit to harm of prostate cancer screening

Text Box 2

PSA-based screening should not be performed in the absence of shared-decision making between clinicians and clients. This effectively discourages organized mass screening in settings where shared-decision making is not part of routine practice (e.g. in health camps, health system promotions, community organizations and religious or political meetings).

What a man needs to know before making a decision about PSA screening:

• There is no perfect screening test

• Screening may have associated harms

• Prostate biopsy & treatment of prostate cancer have

associated risks

Text Box 3

Men considering a screening test for prostate cancer should be aware of several facts:

1. Prostate gland anatomy and function

2. The ratio of benefit to harm of screening:

Evidence shows that the absolute benefits of prostate cancer screening are modest for men age SS to 69 years, while the harms are substantial (Eastham et al, 2003).

a) Putative (evident) mortality benefit of screening

The lifetime risk of prostate cancer is 1 in 6 men. Diagnosis is made in 1 in 9 men and out of these, only 3% of these will die of prostate cancer. (ACS, 2018). Men should consider the threat posed by prostate

cancer and weigh this against other potential life-threatening conditions that they may have. The ratio of benefit to harm can be improved by considering the age and health status of the individual (Welch et al, 2009), and a man’s personal preferences.

b) Harms of screening

PSA screening can lead to psychological harm and biopsy related com-

plications. The greatest harm associated with prostate cancer

screening is the detection of cancers that would otherwise have

remained undetected without screening (over-diagnosis), subsequent

treatment of these cancers (over treatment) and the

associated side effects from a treatment that does not improve survival.

In addition, prostate biopsies and treatments targeting localized

prostate cancer have adverse effects, including pain, fever, bleeding,

infection or problems urinating, with possible need for hospitalization

(Carlsson et al, 200S and Loeb et al, 2012).

3. The likelihood of false-positive and false-negative results

• No screening test is perfect. DRE is not very sensitive and will miss

many early prostate cancers. PSA test can generate a

significant number of false positive results due to low specificity. A

high PSA often leads to a biopsy being performed with many ending

up negative, exposing the patient to the side effects of biopsy

procedures.

• PSA cut-off determines the rate of false positives. Cut-off points of

<4.0 ng/mL can lead to higher rates of false positives (Volk et al, 2007;

Schroder et al, 2009).

4. Description of options & follow-up tests after abnormal PSA is detected. These are articulated below under the discussion on biopsy trigger

5. Treatment options & outcomes for early and late prostate cancer and their possible complications: Possible treatment outcomes in men diagnosed with prostate cancer include:

• Recurrent cancer that will progress despite their treatment

• No evidence of disease recurrence, but no benefit from treatment

either because their cancer was never destined to progress

• No evidence of disease recurrence because their cancer was cured.

Complications of biopsy and treatment in patients screened include, but are not limited to the following: Serious cardiovascular events, deep venous thrombosis or pulmonary embolus, erectile dysfunction, incontinence, and even death (Eastham et al, 2003).

WHO SHOULD BE SCREENED

Men to be screened include:

• ≥40 years, of African descent

• 55-69 years, of Caucasian or Asian origin

• 40-55 years, with a family history of prostate cancer

Text Box 4

Decisions regarding prostate cancer screening should be individualized, based on per- sonal preferences and an informed decision regarding the uncertainty of benefit and the associated harms of screening. The likelihood of prostate cancer in an individual with a family history of the disease increases directly with the number of affected first degree relatives, and is higher if the disease occurred in multiple generations and/or was diagnosed at an early age (below age SS years) as compared to a diagnosis in a sin- gle generation at an older age (Mohan et al, 2011).

These guidelines DO NOT recommend routine screening for the following groups:

• Men aged ≤40 years – due to the low prevalence of disease in this age

group

• Men aged 40 – 54 years at average risk – Caucasians and Asians

• Men age 70 years and above -Though they have a high prevalence

of prostate cancer, they also have a greater risk of life-threatening

co-morbidities and over-diagnosis compared to younger men.

• Any man with a life expectancy less than 10-15 years

FREQUENCY OF SCREENING BY AGE

Symptoms & Age PSA level Frequency of testing
• Asymptomatic & 55-69 years

• 40-54 years with a family history of prostate cancer

• Age ≥ 40 years with a family history of

prostate cancer

A 1 ng/ml Every two years*
1- 4ng/ml Every year
>60 years 2ng/ml Every 2 years

Source: Mottet et al, 2017 and Conford et al, 2017

*Evidence suggests that annual screening is not likely to produce significant incremental benefits when compared with a two-year screening interval (Kerkhof et al, 2010).

BIOPSY TRIGGER

• PSA > 10ng/ml – generally should lead to a biopsy.

• PSA 4 – 10ng/ml – require further interrogation with adjunctive studies like

multi-parametric MRI of the prostate. In addition, DRE, PSA derivatives (PSA density and

age specific reference ranges) and PSA kinetics (velocity and doubling time), PSA molec-

ular forms (percent free PSA and proPSA), newer urinary markers (PCA3), and prostate

imaging should be considered secondary tests (not primary screening tests) that can

help to guide on the justification for a prostate biopsy.

Interpretation of PSA results

• There is no PSA level below which a man can be informed that he does not have prostate cancer. Rather, the risk of prostate cancer, and that of high-grade disease, is continuous as PSA increases (Carter et al, 1997). The urologist should consider factors that lead to an increased PSA including prostate volume, patient’s age, inflammation, ratio of total to free PSA, PSA velocity and PSA doubling time, rather than using an absolute level to determine the need for a prostate biopsy.

• The use of antibiotics to reduce PSA levels in otherwise asymptomatic men is

strongly discouraged, and this practice could lead to an increased

risk of post-biopsy sepsis. A patient with urinary symptoms should be treated

for the infection and the PSA re-confirmed.

• Use of Finasteride or 5 alpha reductase inhibitors can reduce the PSA level by

50%, the PSA result needs to be interpreted using the PSA ratio.

• Ideally the PSA should be done in the same laboratory to avoid inter-

laboratory variations.

Age-Specific Reference Range For Serum PSA

Reference Range
Age Range in

Years

African-Americans Asians Whites/Caucasians
40 – 49 0 – 2.0 ng/ml 0 – 2.0 ng/ml 0 – 2.5 ng/ml
50 – 59 0 – 4.0 ng/ml 0 – 3.0 ng/ml 0 – 3.5 ng/ml
60 – 69 0 – 4.5 ng/ml 0 – 4.0 ng/ml 0 – 4.5 ng/ml
70 – 79 0 – 5.5 ng/ml 0 – 5.0 ng/ml 0 – 6.5 ng/ml

No local data hence this is adopted from international data: (Oesterling et al, 1993 and

Dalkin et al, 1993)

WHO SHOULD DO THE SCREENING?

A general practitioner can prescribe a PSA test in a well-informed patient.

Patients with a PSA >4ng/ml regardless of other parameters, should be referred to a

urologist for further management. The final diagnosis of prostate cancer must be

histological after a biopsy is done.

SCREENING METHODS

The standard method of early detection for prostate cancer relies on these 3 tests:

1. Serum PSA test

2. Digital rectal examination (DRE)

3. Transrectal ultrasonography (TRUS) guided biopsy

Text Box 5

SCREENING AT VARIOUS HEALTHCARE LEVELS

A PSA test should be available from Level 4 hospitals and above, and at accredited

private facilities.

Follow up of PSA testing should ideally be in the same laboratory. A high PSA should be

re-confirmed in the same laboratory.

Most prostate cancers are located in the peripheral zone of the prostate. DRE may not pick small, central or anteriorly-located cancers. DREs are also subjective. Performing a DRE does not significantly increase PSA levels.

Definitive diagnosis of prostate cancer depends on the histopathologic verification of adenocarcinoma in prostate biopsy cores or operative specimens. Transrectal ap- proach is used for most prostate biopsies but a trans-perineal approach can be used for patients without a rectum (due to a previous resection of the rectum). The minimum number of core samples required to make a proper diagnosis is 10 (Extended prostate biopsy protocol).

Algorithm for Prostate Cancer Screening and

Early Detection

REFERENCES

American Cancer Society Facts & Figures 2018. American Cancer Society. Atlanta, Ga. 2018

Carlsson S, Aus G, Wessman C,et al: Anxiety associated with prostate cancer screening with special reference to men with a positive screening test (elevated PSA): Results from a prospective, population-based, randomised study. Eur J Cancer 2007; 43: 2109

Carter HB, Epstein JI, Chan DW et al: Recommended prostate-specific antigen testing in- tervals for the detection of curable prostate cancer. JAMA 1997; 277: 1456.

Cornford et al (2017). EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic and Castration-Resistant Prostate Cancer. European Urology 71 (2017) 630-642. http://dx.doi.org/10.1016/j.eururo.2016.08.002

Dalkin Bl, Ahmann FR,Kopp JB : Proste specific antigen in men older than 50 years without clinical evidence of prostatic carcinoma. J Urol 150:1837-1839,1993

Dickstein RJ, Kreshover JE, Milose JC, Gignac GA: Metastatic prostate cancer at diagnosis: Clinical presentation in the post-PSA era, JCO 2009 27:15S, e16159-e16159

Eastham JA, Riedel E, Scardino PT et al: Variation of serum prostate-specific antigen levels:

an evaluation of year-to-year fluctuations. JAMA 2003; 289: 2695

GLOBOCAN 2018 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Sep 12. doi: 10.3322/caac.21492.

Gulati R, Gore JL and Etzioni R: Comparative effectiveness of alternative prostate-specific antigen–based prostate cancer screening strategies: model estimates of potential bene- fits and harms. Ann Intern Med 2013; 158: 145

Gulati R, Mariotto AB, Chen S et al: Long-term projections of the harm-benefit trade-off in prostate cancer screening are more favorable than previous short-term estimates. J Clin Epidemiol 2011; 64: 1412.

Hugosson J, Carlsson S, Aus G et al: Mortality results from the Goteborg randomised pop- ulation-based prostate-cancer screening trial. Lancet Oncology 2010; 11: 725

Kerkhof M, Robool MJ, Cuzick J et al: Effect of the correction for non-compliance and con- tamination on the estimated reduction of metastatic prostate cancer within a random- ized screening trial (ERSPC section Rotterdam). Int J Cancer 2010; 127: 2639.

Loeb S, van den Heuvel S, Zhu Z et al: Infectious complications and hospital admissions after prostate biopsy in a European randomized trial. Eur Urol 2012; 61: 1110

Mohan R, Beydoun H, Beydoun M et al: Self-rated health as a tool for estimating health-adjusted life expectancy among patients newly diagnosed with localized pros- tate cancer: A preliminary study. Qual Life Res 2011; 20: 713

Mottet et al (2017). EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part I: Screening, Diagnosis and Local Treatment with Curative Intent. European Urology 71 (2017) 618-

629 .http://dx.doi.org/10.1016/j.eururo.2016.08.003

Moyer VA on behalf of the US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med 2012; 157: 120.

Oesterling JE, Jacobsen SJ, Chute CG, et al: Serum prostate specific antigen in a com- munity based population of healthy men: Establishment of age specific reference ranges. JAMA 270: 860-864,1993

Schroder FH, Hugosson J, Roobol MJ et al: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009; 360: 1320

Staging and grading of prostate cancer. Retrieved from http://urotoday.com/2014-09-

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Volk RJ, Hawley ST, Kneuper S et al: Trials of decision aids for prostate cancer screening:

a systematic review. Am J Prev Med 2007; 33: 428.

Welch HG and Albertsen PC: Prostate cancer diagnosis and treatment after the intro- duction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst 2009;

101: 1325.

Organizations that have issued guidelines on prostate cancer screening:

• American Cancer Society (ACS)

• American Urological Association (AUA)

European Association of Urology/European Society for

Radiotherapy and Oncology/International Society of Geriatric

Oncology (EAU/ESSTRO/SIOG)

• European Society for Medical Oncology (ESMO)

• National Comprehensive Cancer Network (NCCN)

• U.S. Preventive Services Task Force (USPSTF)

 

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