Welcome to our lecture on biology, incidence, risk factors, and screening. I'm Ken Pienta, Professor of Urology and Oncology at the Brady Urological Institute at the Johns Hopkins School of Medicine. At the end of this first lecture, you will be able to understand where the prostate is in the body. Understand the difference between benign prostatic hyperplasia and cancer, define risk factors for prostate cancer, and understand current prostate cancer screening guidelines. Let's get started. Biology and incidence. The prostate is a gland about the size of a walnut that sits below the bladder. It is only found in men. It is thought to help protect the urinary tract from infections. The prostate is one of the male sex organs. It produces prostate specific antigen, or PSA, an enzyme that helps liquefy the ejaculate. We'll be learning a lot about PSA as a part of our screening guidelines. It's important to note that the prostate is not necessary for erections or for reproduction. It is thought that evolutionarily, it is really there to protect the urinary tract from infections. Many people confuse benign prostatic hyperplasia or BPH with cancer, BPH is not cancer. With age, the prostate often gets larger, this is termed benign prostatic hyperplasia, sometimes it's termed benign prostatic hypertrophy. Either way, men refer to this as BPH. This benign enlargement of the prostate can make it difficult to urinate. It is treated with medicines or surgery, it is not cancer, it is not related to the risk of developing cancer. This is very important to understand. It is a different disease than cancer itself. And is treated very differently. Prostate cancer is the most common cancer in men. One in seven men in the US will be diagnosed in their lifetime. There is approximately 200 to 220,000 new cases diagnosed every year in the US. It is the second leading cause of cancer death in men, approximately 27,000 men die every year of prostate cancer in the United States. An estimated 1.1 million men worldwide are diagnosed yearly with prostate cancer. This represents 15% of the lethal cancers diagnosed in men. 70% of these cases occur in more developed countries. As man live longer, more prostate cancer is diagnosed. Prostate cancer incidence varies more than 25-fold worldwide. The rates are highest in Australia, New Zealand, and Northern America, and low in Asian populations. An estimated 300,000 deaths are attributed to prostate cancer yearly. It is the fifth leading cause of death from cancer in men around the world, representing about 7% of the total cancer deaths for men. Let's step back a second and think about, what is cancer? Cancer means uncontrolled growth. It's a disease caused by uncontrolled division of abnormal cells in a part of the body. Cancer can also be referred to as a tumor. A tumor is defined as a swelling of a part of the body, generally without inflammation, caused by an abnormal growth of tissue. A tumor can be benign or malignant. Cancer is often referred to as a neoplasm. Neoplasm simply means a new and abnormal growth of tissue in some part of the body. Therefore, when you talk about cancer, or people talk about cancer, they use the words cancer, tumor, or neoplasm all to mean the same thing. Prostate cancer is a type of cancer called an adenocarcinoma. Cancers are classified according to the tissue where they originate, there are four main types. Carcinomas arise in epithelial tissue that is found in the internal and external lining of the body. Adenocarcinomas develop in an organ or gland. Squamous cell carcinomas develop in the squamous epithelium of organs, including the skin, bladder, esophagus, and lung. There are other types of cancers. A sarcoma arises from connective tissue that is found in bones, tendons, cartilage, muscle, and fat. Leukemias are cancers of the blood that originate in bone marrow. And lymphomas are cancers of the lymph system. Cancer is a genetic disease. It is caused by an accumulation of detrimental variations in the genome over the course of a lifetime. Most of the time, a single mutation is not sufficient to induce cancer formation. It takes many mutations to the genome. That's what we see here. Cancer is a disease of multiple genetic alterations. In this example, cancer starts when a tumor suppressor gene is inactivated. Over time, cells start to proliferate and more mutations occur. One of those mutations may occur in a DNA repair gene, making mutations more likely. If a mutation occurs in an oncogene, this causes the cells to continue to proliferate. Over time, more genetic damage occurs in cancer forms. Hanahan and Weinberg, starting in 2000, popularized the hallmarks of cancer. The hallmarks talk about what attributes a cancer needs to grow and spread. These hallmarks are outlined here for you. They include cancer cells stimulate their own growth, they resist inhibitory signals that might otherwise stop their growth. They resist programmed cell death. They multiply indefinitely. As they grow, they stimulate the growth of blood vessels to supply nutrients to the tumors. They invade local tissue and spread to distant sites. Cancer cells also have abnormal metabolic pathways, meaning they use energy differently than normal cells do. They evade the immune system. They are genetically unstable. And they are often associated with inflammatory cells around them. These are the hallmarks of cancer. And are present in just about every solid tumor including prostate cancer. It takes time for these genetic mutations to occur and for them to change the cells. So prostate cancer develops over time. And is associated with precursor lesions. You start with normal prostate epithelial cells. They then go through a period where they are associated with inflammatory cells, and the epithelial cells themselves atrophy. This is referred to proliferative inflammatory atrophy or PIA. The cells then start to proliferate and grow, and they form something called high-grade prostatic intraepithelial neoplasia, or high-grade PIN. This is when the cells are growing inside the gland but haven't broken through. PIN eventually breaks through the gland itself and becomes a localized cancer. After the cancer continues to grow for a long enough period of time, it eventually breaks out of the prostate and spreads. It still is unclear how prostate cancer actually starts, what is the insult that starts prostate cancer. But we do know that over time the cancer itself is associated with multiple inflammatory cells, as well as chemo kinds and cyto kinds that help it grow overtime. What I've tried to tell you here is what cancer is, and what prostate cancer is. The take home message is that prostate cancer is an adenocarcinoma that starts in the prostate gland itself, which is a organ that sits under the bladder.
