Prostate cancer eludes effective diagnosis-prognosis

It is undoubtedly hard to hear the news of a cancer diagnosis, but that’s what an estimated 34,540 men heard in India when new cases of prostate cancer were reported in 2020. Prostate cancer is the most frequently diagnosed cancer in 112 countries, followed by lung cancer in 36 countries, and colorectal cancer and liver cancer each in 11 countries.

Although the actual incidence of prostate cancer in India is lower than that in the Western populations, the incidences are now considerably increasing in the urban population. But for a disease as common as prostate cancer, relatively little is known about its aetiology. Established risk factors are limited to advancing age, family history of this malignancy, and certain genetic mutations in tumour suppressor genes called BRCA1 and BRCA2. Mutations in a few DNA repair genes might also be responsible for some hereditary prostate cancers.

Now some gene mutations can be passed from generation to generation (inherited), while some genes mutate during a person’s lifetime, and the mutation is not passed on to the next generation. Most gene mutations related to prostate cancer seem to develop during a man’s life rather than having been inherited. For instance, exposure to radiation or cancer-causing chemicals can cause DNA mutations in many organs, but so far these factors haven’t been shown to be important causes of mutations in prostate cells.

Further, studies have revealed that people who are obese may have a higher risk of prostate cancer compared to people considered to have a healthy weight. In obese people, the cancer is likely to be more aggressive and more likely to return after initial treatment.

Moreover, distinguishing the lethal from nonlethal is the overarching problem in the clinical management of prostate cancer. Many men who develop prostate cancer never have symptoms or undergo therapy and eventually die of other causes. The natural history of prostate cancer is remarkably heterogeneous and still not completely understood.

Particularly for men with prostate cancer that is localised i.e. not thought to have spread outside the prostate, a major issue is that it’s often hard to tell how quickly the cancer is likely to grow and spread. This can affect whether cancer needs to be treated right away, as well as which types of treatment might be good options.

The widespread use of prostate-specific antigen (PSA) screening has led to earlier detection and a dramatic down-staging of prostate cancer at diagnosis but also has resulted in overdiagnosis and overtreatment of this indolent disease. For instance, most men with an elevated PSA level turn out not to have prostate cancer; only about 25 per cent of men who have a prostate biopsy due to an elevated PSA level actually are found to have prostate cancer when a biopsy is done. But then possible side effects of biopsies include serious infections, pain, and bleeding.

Traditionally, prostate cancer is diagnosed using needles inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue. This approach is called a systematic biopsy.

However, ultrasound does not generally show the location of cancer within the prostate. It is mainly used to make sure the biopsy needles go into the gland safely. Therefore, biopsy samples using ultrasound guidance can miss cancer altogether, or identify low-grade cancer while missing areas of highgrade, potentially more aggressive cancers.

Of late, colour doppler ultrasound is being used that may make prostate biopsies more accurate by helping to ensure the right part of the gland is sampled but further studies are still required in this space.

As a result, clinical imaging research needs to be done to address the clinical management problems in prostate cancer. New serum tissue biomarkers with greater sensitivity and specificity can be developed and validated. In addition, novel imaging techniques can be explored for their potential in detecting early disease, guiding tissue biopsy, and planning treatment.