DISCUSS THE VALUE OF PSA & GLEASON SCORE INTHE MANAGEMENT OF CAP PRESENTER: AROJU S.A MODERATOR: DR MAITAMA H UROLOGY DIVISION, SURGERY DEPARTMENT, ABUTH-ZARIA
OUTLINE• INTRODUCTION• BIOLOGY OF PSA• PSA TESTING• GLEASON SYSTEM• GLEASON GRADE & SCORE• PSA & GLEASON SCORE IN CaP MGT• CONCLUSION
Introduction• Prostate is a solid organ located behind the pubic symphysis from the bladder neck to the urogenital diaphragm: 3.5 by 2.5cm & weighs 18 – 26g.• Composed of 20% glandular & 80% fibromuscular stroma
Introduction… www.prostatematters.com• Transition Zone • Anterior Zone• Peripheral Zone • Central Zone
Introduction…• Prostate cancer is the fourth most common male malignancy worldwide, commonest malignancy in males > 65 years• Since the introduction of PSA testing, the incidence of metastatic disease has decreased.
PSA biology• PSA is a well established tumour marker that aids the diagnosis, treatment and follow up of prostate cancer.• Discovered in the early 1970s• First commercial assay was in 1986
PSA biology…• PSA is glycoprotein enzyme secreted into the seminal fluid by the epithelial cells of the prostate gland, and periurethral glands.• Also in women : it’s secreted by the mammary & periurethral glands.
PSA biology…• Role: is the liquefaction of the seminal coagulum by cleaving 2 seminal vesicle– specific proteins, seminogelin I and II, into LMW soluble protein fragments.• The exact mechanism by which PSA accesses the bloodstream remains unknown.
PSA biology…• There is a strong correlation between the volume of prostate & PSA• It is elevated in CAP, BPH, prostatitis, prostatic infarct & prostatic injury.• Organ specific – not disease specific
PSA biology…• PSA may be normal in anaplastic cancer, neuroendocrine tumours, sarcomas, transitional cell carcinoma, lymphoma and 2º cancer.• Normal ; i. total : 0 – 4ng / ml ii. velocity : < 0.75ng / ml /year iii. Density : < 0.15ng / ml
PSA biology…• PSA velocity: rate of change of serum PSA An ↑ PSA is considered significant only when several serum assays are carried out by the same laboratory over a period of at least 18months• PSA density: ratio of PSA to gland volume PSA level are ↑ apprx. 0.12ng/ml/g of tissue
PSA biology…• PSA exist in blood mainly bound to alpha- chymotrypsin and only small portion as free PSA.• Free /total PSA is useful for distinguishing CaP from benign causes of ↑ PSA.• f/t is recommended for mass screening for CaP
PSA biology…• Studies have found that, in general, men with CaP have ↓ “free” PSA than men without prostate cancer.• Typically, men have a percent-free PSA > 25%. 10% - 25% (intermediate range) and < 10% (low)
PSA testing• PSA level has been used as a screening tool for CAP since the mid-1980s.• Currently, first-line screening for prostate cancer consists of DRE & serum PSA levels.
PSA testing…• 30% of men with ↑ PSA will have prostate cancer confirmed by biopsy.• 20% of men with clinically significant prostate cancer have PSA values within the normal range.
PSA testing…• Combined use of DRE, PSA & TRUS- guided prostatic biopsy is most effective for early prostate cancer.• Nevertheless, the finding of a PSA > 10 ng/ml is suggestive of cancer and > 35 ng/ml is almost diagnostic of advanced prostate cancer.
Why do we need screening for Prostate Cancer?1. Rising incidence and mortality rates.2. Aging population.3. Current understanding of pathogenesis limits the use of preventative measures.
Why do we need screening for Prostate Cancer?4. Therapeutic options for metastatic disease are palliative.5. In the pre-PSA era, only 30-40% of patients presented with localized disease.
PSA testing…ACS recommendations• Age 50: men at average risk & ≥ 10yr life expectancy.• Age 45: men at high risk - African american, men with 1st degree relative diagnosed at early age.• Age 40: men at higher risk – multiple 1st degree relatives diagnosed at early age.
PSA testing…Informed consent:• CaP is not always life threatening i. Most CaP grow slowly ii. Many men who died of other causes have autopsy → CaP iii. 1 in 6 diagnosed of CaP 1 in 34 will die of the dx.
PSA testing…Informed consent:• Testing helps some men but in others, it leads to diagnosis & Rx of cancer that would never cause harm.• Side effect of CaP Rx – impotence & incontinence.
Gleason System• The Gleason grading was devised in the 1966 by a pathologist, Dr Donald F Gleason• And members of the Veterans Administration Cooperative Urological Research Group (VACURG).
Gleason System…• The Gleason grading system is based entirely on the histologic pattern of carcinoma cells in H&E stained prostatic tissue sections.• Grade : 1 - 5• Score : 2 - 10
Gleason System…• The 1º pattern is the most predominant in area by simple visual inspection.• The 2º pattern is the second most common pattern.• If only one grade is in the tissue sample, that grade is multiplied by two to give the score.
Gleason System…• If the second grade is less than 3% of the total tumor, the primary grade is doubled to give the GS.• Gleason sum / combined Gleason grade / category score ► synonyms for Gleason score, but histological pattern score was the initial 1974 designation.
Gleason grades Grade 1:The cells are welldifferentiated and areuniformly spaced in atight mass.
Gleason grades…Grade 2:The cancer cells aredifferentiated, but arearranged moreloosely, are moreirregular in shape, andsome cells havespread to otherprostatic tissue.
Gleason grades…Grade 3:The cancer ismoderatelydifferentiated; cellsvary in size and morecells have invadedother prostatic tissue.
Gleason grades… Grade 4:The cancer cells areirregular, distorted,poorly differentiated& considerable spread(invasion) to otherprostatic tissue.
Gleason grades…Grade 5:The cancer cells donot look like normalcells and have spreadin haphazard“clumps” of alldifferent shapes andsizes .
Modified Gleason grades By 1974, data from 1032 patients:• Pattern 1 & Pattern 2 : same as original• Pattern 3. Moderately differentiated glands, may range from small to large, growing in spaced out infiltrative patterns, may be papillary or cribriform.
Modified Gleason grades…• Pattern 4. Raggedly infiltrating, fused- glandular tumour, frequently with pale cells, may resemble hypernephroma of kidney.• Pattern 5. Anaplastic carcinoma with minimal glandular differentiation, diffusely infiltrating prostatic stroma.
Modified GS Conference of International Society of Urological Pathology (ISUP), 2005:• any aggressive cancer seen on the needle biopsies should be incorporated to the GS, even if present in small amount.• Overall Gleason score• Worst Gleason score
Modified GS…• OGS – Sum of the predominant & the most aggressive pattern of all the biopsy cores, treated as one long core.• WGS -
Significance of GS• The Gleason score is used to determine how quickly a tumor may grow or spread.• The time for which a patient is likely to survive following a diagnosis of prostate cancer is related to the Gleason score.
Significance of GS…• Studies have demonstrated that Gleason 4+3=7 disease is much more aggressive than Gleason 3+4=7 tumors.• A study demonstrated that after 5 years of follow up, men treated for Gleason 4+3=7 ► 40% risk of progression Gleason 3+4=7 ►15% risk of progression
Pitfalls of the Gleason Score• The score is subjectively determined by a pathologist.• A biopsy may not provide a representative sample of the entire prostate.
PSA & GS in the management of cancer of the prostate
Diagnosis• Combined use of DRE, PSA & TRUS- guided prostatic biopsy is most effective for early prostate cancer diagnosis.• PSA > 10 ng/ml is suggestive of cancer and > 35 ng/ml is almost diagnostic of advanced prostate cancer.
PrognosisThe Partin Coefficient Tables• Important tools in guiding decisions about effective treatment options for CaP• They are a way of predicting the cancers pathologic stage, which can only be determined after prostatectomy.
Prognosis…The Partin Coefficient Tables• Based on PSA, GS & clinical stage, these tables show the probability of having one of the ffg pathologic stages of CaP: i. Organ confined ii. Capsular involvement iii. Seminar vesicles involvement iv. Lymph node involvement
AUA, 2000 report• PSA level can be used to eliminate some staging investigations:• A patient with CAP without skeletal symptoms & PSA < 10ng/ml may not need radionucleotide studies for bone metastasis bcs the chances are near to zero.
AUA, 2000 report…• Similarly, CT & MRI are not indicated for staging in men with clinically localized prostate cancer and PSA < 25ng/ml.• Pelvic lymph node dissection in staging may not be required in patients with PSA < 10.0ng/ml or PSA < 20ng/ml & the GS ≤ 6.
Treatment Selecting initial treatment requires assessing the risk of the disease spreading or progressing, which is based on: Life expectancy, Comorbidities, Biopsy grade (Gleason score), Clinical stage, and Prostate-specific antigen (PSA)
Treatment… Patients with clinical stage T1c with : Gleason score ≤ 6, PSA < 10ng/ml, density < 0.15ng/ml/g, fewer than 3 positive prostate cores, ≤ 50% cancer in each core, and life expectancy < 20y,Rx : active surveillance
Treatment…Active surveillance PSA every 3mo or at least every 6mo; DRE every 6mo or at least every 12mo; Repeat biopsy within 18mo but as often as every 12mo or if PSA and DRE change.
Treatment… Patients with clinical stage T1-T2a with : Gleason score 2-6, PSA < 10 ng/ml, Life expectancy < 10y,Rx : active surveillance
Treatment… Patients with clinical stage T1-T2a with : Gleason score 2-6, PSA < 10 ng/ml, Life expectancy ≥ 10y,Rx : Radical prostatectomy _+ PLND OR Radiation therapy
Treatment… Patients with clinical stage T2b-T2c with: Gleason score 7, PSA 10-20 ng/ml, Life expectancy < 10y,Rx : Active surveillance OR Radiation therapy _+ ADT
Treatment… Patients with clinical stage T2b-T2c with: Gleason score 7, PSA 10-20 ng/ml, Life expectancy ≥ 10y,Rx : Radical prostatectomy + PLND OR Radiation therapy _+ ADT
Follow-up• Following radical prostatectomy, PSA should be undetectable after about a month.• Cancer recurrence is a PSA > 0.2ng/ml that has risen on at least two separate occasions at least two weeks apart and measured by the same lab.
Follow-up…• PSA velocity & PSA doubling time, both are very significant in determining the aggressiveness of CAP.• Men with ↓ PSA doubling time or ↑ PSA velocity after initial therapy tend to have more aggressive disease, and are more likely to need more aggressive therapies.
Conclusion• Serum PSA has revolutionalized the ability to detect CAP, though disease nonspecific. ↑ specificity : PSA density, velocity, age adjusted reference range.• Gleason score is a good device to determine aggressiveness & prognosticate outcome. However, it’s pathologist subjective
References Smith general urology, 16th edition. Emil A. Tanagho MD, Jack W. McAninch MD,FACS Bailey & loves short practice of surgery, 25th edition. Norman S. Williams, Christopher J. K Bulstrode & P. Ronan O’ Connell. Principles & practice of surgery including pathology in the tropics, 4th edition. E.A Badoe M.D, CH.m, FRCS, DTM&H, FWACS, FGA, DSc, FGCP&S, COV. E.Q Acharpong B.Sc, MS, FRCS, FICS, FWACS, Gleason grading and prognostic factors in carcinoma of the prostate, Peter A Humphrey. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA. Published online 13 February 2004. Percent-Free PSA, Matthew Schmitz, M.D, About.com healths disease and condition, May 04, 2009.