PRECISION THERAPIES TO FIGHT PROSTATE CANCER
More men in India are getting cancers of the prostate, mouth and kidney; more women, cancers of the uterus, breast and thyroid. And the incidence of lung cancer is growing fast among both sexes.
Data from India’s population-based cancer registries lists prostate as the second most common cancer among men in Delhi, Kolkata, Pune and Thiruvananthapuram; third most common in Bangalore and Mumbai; fourth in Chennai, and among the top ten cancers across India, except in the north-eastern states (barring Kamrup district in Assam, where it is sixth).
Since the 1990s, the total number of prostate cancer cases in the country has shot up by over 220%. India’s National Cancer Registry Programme estimates incidence will have grown rapidly by the year 2020.
The current annual percentage increase is 3.4% in Bangalore, 4.2% in Chennai, 3.3% in Delhi, 0.9% in Mumbai and 11.6% Kamrup Urban District, driven in part by changing lifestyles, longer lifespans and increased diagnosis rates. Yet, it’s the least discussed cancer even among oncologists, because of the perception that it afflicts populations in developed nations and is not common among Asians.
RACIAL BIAS
Race does have a role in determining risk. Asians have the lowest risk of developing prostate cancer and men of African descent have the highest, followed by Caucasians. Asian men also have higher survival rates than white males, but Indian men have lower survival rates than Africans and Caucasians, show data from the California Cancer Registry.
Men of South Asian descent, however, are predisposed to aggressive prostate cancer and are 40% more likely to die from it than Caucasians.
“Two genomic studies — on single cell genomics profiling and racial disparity profiling — are underway at the urology department to better understand racial disparities in prostate cancer risk and tumour progression and to identify the molecular drivers of aggressive prostate cancer so as to personalise diagnosis and treatment,” says Dr Ashutosh K Tewari, chairman of urology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, and course director of the 2nd International Prostate Cancer Symposium held at the hospital this week.
Racial disparities remain poorly understood because of poor multicultural representation in the studies done so far. Only 11% of the 498 samples gathered for the world’s largest prostate cancer profiling study were from African-Americans.
“We did a comparative statistical analysis of this data and identified novel differentially expressed genes between men of African descent and Caucasians. The observed differences suggest that prostate cancer in men of African descent may be a different disease subtype, which warrants a more comprehensive profiling study,” says Dr Tewari. “We need similar studies on south Asian populations.”
LIFESTYLE RISKS
Factors such as age, family history, smoking, obesity, physical inactivity, diabetes, height and DNA repair mutations in some genes — such as the BRCA2 gene also linked with breast and ovarian cancers — are also associated with higher risk. Rapid industrialisation and changing lifestyles are expected to drive numbers up too.
“In 2015, 1.6 million men worldwide were diagnosed with prostate cancer. It’s the leading cancer in 103 countries and the biggest cause of cancer deaths in 29 countries, killing around 366,000 men in one year,” said Lorelei Mucci, associate professor of epidemiology at the Harvard School of Public Health.
With the standard screening method — a digital rectal exam and blood tests for prostate-specific antigen (PSA) — throwing up false positives because PSA levels also get elevated by many benign conditions such as an inflamed prostate, a biopsy is done to confirm cancer.
Since a biopsy has its own challenges because of intra-tumour heterogeneity, and clinicians are using genomic analysis, diagnostic imaging and tumour bio-markers to confirm the severity of disease and provide personalised treatment options.
The first immunotherapy agent approved by the USFDA for cancer treatment was for prostate cancer, but these are being tested largely on high-risk patients.
At Mount Sinai, Dr Tewari’s team uses a three-pronged approach of employing genomics to provide precision immunotherapy, using combination immunotherapy and anti-cancer techniques to enhance therapeutic benefits of high-intensity focus ultrasound, and genetically engineering the patient’s T lymphocyte cells — a subtype of white blood cells that seek and destroy cells that are infected or cancerous — with tumour-targeting strategies.
“To optimise treatment, we need strategies to stop tumours from proliferating in patients with early but clinically localised aggressive cancers,” Dr Tewari says.