Page created on April 20, 2019. Last updated on May 13, 2019 at 17:57
Prostate cancer is the most common form of cancer in men, accounting for around 25% of cases. However, it causes only 9% of all cancer deaths, which shows that it has a low mortality. This is owed mostly to regular screening of PSA levels and digital rectal examination.
The efficacy of screening for prostate cancer is debated. The reason for this is that not all cases of prostate cancer are aggressive and fatal; many cases follow a very indolent course with few clinical symptoms. Screening (especially with PSA) can’t differentiate between prostate cancers that would become aggressive and those that wouldn’t, and so many people who would develop clinically indolent prostate cancer undergoes potentially life-changing treatment which may be worse than the symptoms of the cancer would have been. Indeed, prostate cancer is often found incidentally on autopsy, and more people die with prostate cancer than of prostate cancer.
The following are risk factors for developing prostate adenocarcinoma:
- Age > 50 years
- Positive family history
- African-American race
- Scandinavian race
- Diet high in animal fat
Pathogenesis: Prostate cancer, like BPH, depends heavily on androgens. Most cases of prostate cancer regress temporarily after anti-androgen therapy. This often leads to the cancer developing a mutation that allows it to function even in the absence of androgens.
Fusion of the genes TMPRSS2 and ETS occurs in 50% of prostate cancers. Inactivating mutations of the tumor suppressor PTEN is also frequent.
Clinical manifestations: As most (70 – 80%) prostate cancer grows in the peripheral zone of the prostate, lower urinary tract symptoms are rarely seen until the later stages, when the cancer has grown. Advanced-stage prostate cancer may present with general cancer symptoms like fatigue and loss of appetite.
Prostate cancer most frequently metastasizes into the spine, especially the lumbosacral part, causing lower back pain. It also metastasizes to parailiac lymph nodes.
Diagnosis: Screening ideally begins at the age of 50, involving digital rectal examination (DRE) and serum PSA. Those 70 – 80% of cancers that occur in the peripheral zone may be discovered during routine digital rectal examination screening; most prostatic cancers aren’t palpable on DRE though. Definitive diagnosis is based on needle biopsy of the prostate.
PSA is an enzyme that is produced only by the prostatic glandular epithelium, which is why its level correlates to the number of prostatic glands in the body. Its level can also be increased in prostatitis or BPH, so it’s not specific for cancer. PSA is considered elevated above 4 ng/mL.
As explained earlier, it is uncertain whether PSA screening actually decreases prostate-cancer related deaths. Elevated PSA might not necessarily correlate to a clinically active cancer, so its usefulness should be determined on a case-by-case basis. PSA does have great value in measuring the effectiveness of therapy though.
Histology: 95% of prostate cancers are acinar adenocarcinomas. The cells of the cancerous prostatic glands have prominent nucleoli and show atypia. These glands are small and are also not surrounded by basal cells, unlike the healthy prostatic glands.
Grading: Grading depends on the Gleason system, which assigns each case a “score” based on their histology. Prostate cancers are divided into 5 grades, depending on the glandular architecture (and not the nuclear atypia). In grade 1 the glands look almost like normal glands while in grade 5 there are only a few or no glands (correspond to anaplasia).
Most prostatic adenocarcinomas show more than one pattern of differentiation. A grade is assigned to the pattern there is most of on a histological slide, and another grade is assigned to the pattern there is second most of. These two numbers are then combined to give a Gleason score.
For example, if 60% of a prostate adenocarcinoma is grade 3 and 30% is grade 5, the combined score will be (3 + 5) = 8. The worst possible score is 10 and the best possible score is 2.
Treatment: In many cases of prostate cancer a “watch and wait” approach might be safer than outright treating the tumor. This is especially true for elderly people with comorbidities or people with a less than 10-year life expectancy, as the treatment might be worse than the disease.
If the cancer hasn’t yet spread, local irradiation or radical prostatectomy should be considered. If the cancer already has metastasized, chemotherapy and antiandrogen therapy should be considered.
Prostatic intraepithelial neoplasia (PIN) is the precancerous lesion for prostate cancer. We distinguish two types: low-grade PIN and high-grade PIN.
Low-grade PIN is found in a large number of adults, even young adults. This form virtually never progresses into prostate cancer.
High-grade PIN is associated with an increased risk of prostate cancer. It involves a disrupted basal layer of the prostatic glands, prominent nucleoli and increased density of the chromatin of the glandular cells.