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neo_prostate

prostate cancer

introduction

  • typically a disease of men over age 50 years, but those at risk tend to be advised screening from age 40 years
  • localised cancer is usually asymptomatic and is usually discovered by the detection of a nodule on rectal examination, or finding an elevated prostate specific antigen (PSA) level.
  • most prostatic cancers arise peripherally - away from the urethra, and thus urinary symptoms occur late
  • in the past, a relatively common presentation was acute paraplegia from spinal metastases but such late presentations are now uncommon with PSA screening.

risk factors

  • age
    • incidental prostate cancer at autopsy is discovered in 20% of men in their 50's, to 70% in their 70's
  • race
    • incidence is higher in blacks, whilst being uncommon amongst Asians, although incidence increases with adoption of Western lifestyles and diet.
  • family history
    • men with one 1st degree relative with prostate cancer have 2x risk, while those with two 1st degree relatives have 5x risk
    • men with a strong FH tend to develop cancer at an earlier age
    • variations in the length of CAG segment of the X-linked AR gene (the nuclear androgen receptor)
      • longer it is the lower the risk (eg. Asians)
      • rate of development of cancer is inversely related to length of repeats in mouse models
    • a small proportion of cases relate to mutations in the tumour suppressor BRCA2 gene and men with this have a 20x risk
      • those who also have IDC-P (intraductal carcinoma of the prostate) have a very high risk of aggressive cancer
    • men with the highest levels of “cell cycle progression” (CCP) genes - ones that encourage cells to grow - were three times more likely than those with the lowest levels to have a fatal form of prostate cancer.
    • red-headed males appear to have 50% less risk
  • hormonal levels
  • environmental influences
    • higher risk appears to relate to:
      • diet:
        • high fats
        • high blood concentrations of the fatty acids EPA, DPA and DHA due to eating fatty fish or taking fish-oil supplements appears to increase risk of the dangerous high-grade prostate cancer by 71% 1)
        • vitamin E raised the prostate cancer risk, particularly in those with low selenium levels and appears to more than double the risk for aggressive high grade cancers 2)
        • selenium supplements in men with normal selenium levels (ie. “toxic doses”) appears to raise risk for aggressive high grade cancers by almost double 3)
    • lower risk appears to be from:
      • diet: lycopenes, soy products, and vitamin D while eating mushrooms 3x/wk appears to reduce risk by 17%
  • obesity
    • risk of aggressive cancer doubles if > 20kg weight gain in adult life
  • 5ARI medications such as finasteride:
    • the REDUCE trial and the Prostate Cancer Prevention Trial appeared to show that use of 5ARI agents, whilst not affecting overall risk of prostate cancer, did appear to INCREASE risk of Gleason 8-10 high grade cancers, although incidence of these cancers was less than 2% in both studies.
  • vasectomy
    • it seems vasectomy at age < 38yrs increases risk of aggressive prostate cancer by ~20% and when done at any age, 10% increased risk for all high grade prostate cancers 4)

screening

serum prostate specific antigen

urine EN2

Prostate Urine Risk (PUR)

  • experimental test as at 2019 but appears to be able to detect aggressive prostate cancer cases 5 yrs earlier than standard clinical methods and thus may help to reduce the need for harmful biopsies

digital rectal examination

  • may detect some early tumours because of their posterior location but it has low sensitivity and specificity

transrectal ultrasound

  • poor sensitivity and specificity
  • significant risk of potentially life threatening post-procedure sepsis
  • typically, a transrectal needle biopsy is required to confirm the diagnosis (NB. needle biopsy is NOT sensitive for BPH!)
  • current methods are effectively “blind” biopsies as the operator cannot “see” a tumour or precisely where the biopsy needle should be placed which results in a relatively high false negative rate
    • in 2012, a new device called Artemis was developed with the help of MRI imaging to generate a 3D ultrasound image to better enable more acurate biopsy needle placement in a tumour and hopefully this may reduce the false negative rate

MRI scan

  • may be better than prostatic biopsy for ruling out cancer and also for locating actual lesion
  • may be indicated if high PSA and a negative biopsy
  • some argue it should be done BEFORE a biopsy and hopefully a biopsy can be avoided, or if done, have fewer false negative results
    • MRI appears to be able to reduce need for biopsy by 25% and reduce false positive diagnoses of cancer by 5%
    • sensitivity for aggressive cancers was 93% compared to US guided biopsy sensitivity of only 48%
    • MRI will miss 10% of harmful cancers while US guided biopsy without prior MRI misses up to 30% 5)

grading

Gleason system

  • 5 grades on the basis of glandular patterns of differentiation
  • Grade 1 is the most well-differentiated tumours
  • Grade 5 shows no glandular differentiation
  • most tumours have a dominant Grade and a secondary Grade, and these are added together to give a Gleason Score (range 2-10).

staging

  • stage T1 = clinically inapparent lesion incidentally found
  • stage T2 = organ-confined cancer
  • stage T3a = extension outside the prostate with seminal vesicle invasion
  • stage T3b = extension outside the prostate without seminal vesicle invasion
  • stage T4 = direct invasion of contiguous organs
  • N1 = lymph node involvement
  • M1 = distant metastases

treatment

genomic sequencing

Rx of localised prostate cancer

radical prostatectomy vs observation

  • the following is data from the PIVOT study which enrolled 731 patients 6)
  • importantly, enrolments for the study occurred in 1994-2002 and since then PSA levels and biopsy interpretation has changed which will effect how the results of this study could be interpreted, however, the authors conclude that the findings support observation for men with low risk disease (which includes some 2/3rds of all men diagnosed with prostate cancer although currently 90% of prostate cancer patients receive either surgery or radiotherapy).
  • by study end (after 15 years), death from any cause was similar in both groups (47% in surgery group vs 49.9% in observation group) and death attributable to prostate cancer or its treatment was similar in both groups overall with a small mortality benefit in the surgical group (5.8% in surgery group vs 8.4% in observation group)
  • 21.4% of the surgical group had a significant adverse event within 30 days of surgery (eg. infection, bleeding, DVT/PE or need for persistent IDC)
  • at 2yrs, 17% of surgical group had urinary incontinence (vs 6% of observation group)
  • at 2yrs, 81% of surgical group had erectile dysfunction (vs 44% of observation group)
  • at 15yrs, bone metastases occurred in 4.7% of those who had radical prostatectomy vs 10.6% of those observed, however, the differences in cumulative incidence between the groups changed little after 8 years of follow up
  • high risk tumours:
    • radical prostatectomy gave a non-significant absolute reduction in mortality of 6.7 percentage points compared with observation
  • intermediate risk tumours
    • defined as PSA 10.1-20.0 ng/ml, Gleason score 7, or stage T2b tumour
    • radical prostatectomy gave a 31% relative reduction in all-cause mortality of 6.7 percentage points compared with observation (hazard ratio 0.69, CI 0.49-0.98, absolute risk reduction 12.6 percentage points)
  • low-risk tumours:
    • defined as PSA 10ng/ml or less, Gleason score 6 or less, and stage T1a-c or T2a
    • radical prostatectomy gave a 15% non-significant INCREASE in mortality compared with observation (hazard ratio 1.15, CI 0.80-1.66)
neo_prostate.txt · Last modified: 2019/09/09 00:19 by gary1