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Outsmarting a cancer

Since Prostate cancer may occur without symptoms, all men should get screened at 50 years. Men with a family history should do it at 40 years. Dr Ashutosh Tewari and Dr Abhishek Srivastava write. Rate per 100,000 | Number crunching | Troubling triggers

health and fitness Updated: Apr 24, 2011 01:33 IST

One in six men currently living in the US are at risk of developing this cancer, which afflicted around 218,000 Americans and killed 32,000 in 2010. Rates of prostate cancer differ over 50-fold among various international populations, standing at 137/100,000 people among African Americans as compared to 8/100,000 people in India and 2/100,000 in China.

This, however, does not mean that incidence is higher in the US and other Western countries. Countries that do not employ PSA testing typically have a much lower rate of prostate cancer compared to those that do.

In the US, increased frequency of prostate biopsies done in men with no symptoms but high prostate specific antigen (PSA) levels - high blood levels of this protein produced by the prostate gland is an indicator of cancer - led to a rapidly rising incidence in the early 1990s.

After an initial peak, incidence rates fell, but they have persisted at a rate nearly twice that recorded in the pre-PSA era. This also led to a 'stage shift' and now more people are being diagnosed in the early stages. The argument against routine PSA screening is that many of these so-called 'early' cancers, if left undetected, would never cause problems during the patient's lifetime.

Screening and other tests
PSA: Screening is done using this simple blood test that measures PSA levels. Apart from prostate cancer, there are many other reasons for raised PSA, such as benign prostatic hyperplasia (BPH or enlarged prostate), prostatitis, and damage to the prostate.

People with an abnormally value should not panic but requires further assessment by a urologist (a doctor who specialises disorders of the urinary, bladder and prostate). PSA tests are usually repeated. In some cases, you may be treated for a prostate infection before repeating the test. If the PSA remains elevated, a prostate biopsy is usually recommended.http://www.hindustantimes.com/Images/HTEditImages/Images/24_04_11-prostate.jpg

Since some drugs such as 5 alpha-reductase inhibitors (finasteride and dutasteride) to treat BPH, statins to lower cholesterol, non-steroidal anti-inflammatory drugs (NSAIDs) for pain lower PSA levels in men taking them, PSA testing is still controversial.

Free PSA: Most PSA in the blood is bound to proteins, but a small amount is free. In men with prostate cancer, the ratio of free unbound PSA to total PSA is decreased. Typically, percent-free PSA is above 25%. Between 10% and 25% is an intermediate range and below 10% is low.

PSA Velocity: Many prostate cancer experts now consider not only the PSA level, but how fast it is changing when determining whether to order further tests, when to start treatment, or what to tell their patients about prognosis. Numerous studies have now shown that a high PSA velocity (for example rapid doubling time of PSA or a rise of 0.35 ng/mL or more per year) may signal a rapidly growing cancer regardless of how high the absolute PSA level is.

PCA3 (Prostate Cancer gene 3) is a gene that is overexpressed in prostate cancer and can be detected by simple urine test after rectal examination. The PCA3 test is a relatively new way of assessing prostate cancer risk and can help in making better biopsy decisions in the diagnosis of prostate cancer. PCA3 is not only prostate-specific, but also prostate cancer specific. Unlike the PSA test, the PCA3 score is not affected by the size of the prostate. The PCA3 test is also less affected by urinary infections, which can make the PSA completely unreliable. Studies are undergoing to validate this test in clinical setting.

Rectal examination: A rectal examination is often recommended, along with PSA tests, as many of the causes outlined above can be diagnosed with such an examination.

Prostate biopsy: A prostate biopsy involves having an ultrasound scan done through the rectum and using a needle to obtain tissue samples from the prostate gland. The biopsy is usually performed in the office by a urologist. After the procedure, most men feel sore and may see blood in their urine or semen.

The reason why screening is important is that prostate cancer is asymptomatic in most men, and hence there are no clues to the patient that he might have the disease.

Magnetic Resonance Imaging (MRI): MRI is not widely used as a first-line approach to diagnose prostate cancer. However, it may be useful to target biopsy in patients with repeated negative biopsies but PSA levels indicative of cancer. MRI has good diagnostic capability for pretreatment staging of prostate cancer especially stage 3 and stage 4 disease. Recently, the addition of new technologies such as perfusion imaging, diffusion imaging, dynamic contrast enhancement, spectroscopy and multiparametric MRI (combination of all) to simple MRI imaging has enhanced the capability of MRI to differentiate between tumour and normal tissue.

Risk factors for prostate cancer
Age
: A review of international autopsy studies showed widespread prevalence of hidden prostate cancer even in young men with rates of 20% at age 30. However, clinically diagnosed prostate cancer rarely occurs before the age of 40, with an exponentially increasing incidence after age 60.

Ethnicity: Prostate cancer is more common in Black than Caucasian or Hispanic men, probably because of a combination of genetic and dietary factors. It also typically occurs at a younger age in African-American men as compared to other populations. Many studies have found that African-American men have higher serum PSA levels, worse Gleason scores (Box 2), and more advanced stages of disease at the time of diagnosis. Our research shows Indian men also have a greater tendency for worse tumour types in both the pre-operative biopsy and the final prostate specimen after surgery.

Genetics: Although there is evidence of a strong genetic component, identifying specific genes that underlie prostate cancer has proven challenging as it is a multifactorial and polygenic (many genes) disease. Our group is the first group in the world to do genetic sequencing of the entire prostate cancer cell genome, recently published in Nature.

Men who have a close relative (a father or brother) with prostate cancer are at higher risk, as are those with female relatives with breast cancer related to BRCA, the breast cancer gene.

Diet: A diet high in animal fat may be an important factor. In particular, intake of large amounts of alpha-linoleic acid and low amounts of linoleic acid appear to increase prostate cancer risk; this combination is common in red meat and some dairy products.

A high vegetable diet, on the other hand, offers protection against it. High intake of cruciferous (leafy) vegetables (particularly broccoli and cauliflower) appears to lower the risk of aggressive prostatic tumors. Tomato-based products are rich in lycopene, which is a potent anti-oxidant, and linked to lower prostate cancer risk.

Phytoestrogens such as those found in soy foods reduce prostate cancer risk. A diet rich in soy products is common in Asian countries and believed to be one of the reasons for the lower incidence of prostate cancer in Asians living in Asia compared to Asian migrants to Western nations.

Infection and chronic inflammation: Several infections are believed to contribute to the development of prostate cancer. Some studies have shown that men with prostatitis - inflammation of the prostate gland - and those with a history of sexually transmitted infections such as syphilis or gonorrhea are at a slightly higher risk of developing prostate cancer.

We would like to thank Dr. Prasanna Sooriakumaran, Dr. Sonal Grover and Robert Leung - our team members in New York their contribution.

Four stages of cancer
It's classified into four stages based on the extent of disease.
Stage 1: The cancer is microscopic and is only in the prostate gland, cannot be felt during a rectal examination and is not visible by imaging.
Stage 2: The tumour has grown large enough within the prostate gland to become either palpable during a examination or visible on imaging studies.
Stage 3: Prostate cancer has spread outside the prostate, but only barely. It may now involve nearby tissues such as the seminal vesicles, where semen is stored.
Stage 4: The cancer has spread to other tissues, such as the lymph nodes, the bones, liver, or lungs.
Histological classification of prostate cancer
The Gleason grading system (made up of two scores ranging from 1 to 5 each) is used to grade the prostate cancer down the microscope. It provides an estimate of the aggressive potential of the tumor and has been shown to correlate with prognosis of the disease.
Gleason 3+3: tumor is low grade (best prognosis)
Gleason 3+4 / 3+5: tumor is mostly low grade with some high grade
Gleason 4+3 / 5+3: tumor is mostly high grade with some low grade
Gleason 4+4 / 4+5 / 5+4 / 5+5: tumor is all high grade (worst prognosis)