Prostate Cancer

What is a prostate? Where is the prostate?
What illnesses are associated with the prostate?
What is PSA?
What do we learn from a biopsy?
I have been diagnosed with prostate cancer. Is it something I did?
How does the Gleason grading system work?
What is a radical prostatectomy?

What is the prostate? Where is the prostate?
The prostate is a nonessential, secretory, secondary sexual organ found in all male mammals. Among the secretory products of the prostate is a protein known as prostate-specific antigen (PSA). Females do not have prostates, although tiny secretory organs next to the urethra share some homology to the prostate. These female organs, named for Scottish gynecologist Alexander Skene, also produce PSA. 

Anatomically and pathologically, mammalian secondary sexual organs vary greatly from species to species. For instance, the human has a single prostate attached to paired, nonessential secretory organs known as seminal vesicles. By contrast, the dog has only a prostate. In the opossum, the prostate is composed of a series of small glands around the urethra. By contrast, in the human, the prostate is a single, fused, midline structure wrapped around the urethral segment positioned between the urinary bladder and pelvic floor, as shown in the cartoon. Together, the prostate and seminal vesicles produce the liquid portion of semen and are thought to be required for fertility. The necessity of prostates in fertility is debatable, as in the rat, which has several prostates, surgical excision of the lateral prostates has no meaningful effect on fertility. 

As shown in the cartoon, the human prostate is positioned deep in the pelvis behind the heavy pubic bone and enmeshed in other structures. The position of the prostate complicates surgical access. The pointed prostatic apex is pressed against the very bottom of the pelvic cavity, where it attaches to the urethra. The posterior prostatic surface rests against the rectum. Superiorly, the wide prostatic base rests against the bladder neck. Anteriorly, the prostatic apex is covered by the very vascular dorsal venous plexus of Santorini. Access to the dorsal venous plexus is restricted by paired, tough ligaments on each side connecting the prostate to the undersurface of the thick pubic bone. Anterior to the prostate is a thin fascial layer covered in fat. Behind the prostate and seminal vesicles is the thick Denonvillier's fascia. Resting over all these structures is the bladder, behind which are the ureters. Most laterally are the iliac veins, iliac arteries, and lymph nodes.

What illnesses are associated with the prostate?
Prostatitis, an often painful inflammation of the prostate, is fairly common and is seen in relatively young men. Benign growth of the prostate (BPH) increases in incidence as men age. BPH is sometimes associated with frequent urination, weak urinary stream, night-time urination, and other symptoms. Cancer is common in the prostate and also increases in incidence as men age.

What is PSA?
PSA is prostate-specific antigen, a protein produced by the cells of the prostate that form the liquid secreted by the prostate during ejaculation. PSA is also produced to lower concentrations in other types of cells in the body. PSA is found in very high concentrations in the ejaculate, but normally only a small portion seems to leak into the bloodstream. The concentration of PSA in the blood provides an estimate of the risk of having prostate cancer, which provides the rationale for measuring PSA in asymptomatic men. For instance, a PSA concentration between 2.5 and 10.0 ng/ml is associated with a probability cancer on a biopsy of approximately 25%. Like any test, PSA must be interpreted in context, as infections, medications, and other factors can cause fluctuations in the blood concentrations. PSA is not a diagnostic test. To diagnose prostate cancer today requires a biopsy.

What do we learn from a biopsy?
A biopsy of the prostate is generally done under ultrasound guidance and yields tissue cores, such as the unstained core shown in the photo. After retrieval, cores are fixed, typically in formaldehyde, and then placed into cassettes for embedding in paraffin, slicing, and staining prior to pathological evaluation. The ultrasound image identifies different regions of the prostate and the seminal vesicles, which allows properly distributed and targeted sampling. The tissue cores, representing samples of prostate, are submitted for microscopic evaluation by a pathologist, who looks for cancer, infection, inflammation, drug effect, premalignant lesions, and benign hyperplasia. Because it is a sample, a biopsy is not necessarily a complete and fair representation of a prostate: a positive biopsy shows cancer, but a negative biopsy provides no real assurance that there is no cancer. It is also worth noting that biopsies are open to interpretation by pathologists, whose skills and experience vary. Because so much of the patient's decision depends on correct interpretation of biopsy findings, surgeons work closely with pathologists and very often review the slides directly with them.

After analysis of prostatic tissue, the pathologist issues a written report of his findings. At a minimum, a prostate biopsy report must indicate the number and length of cores examined, the prostatic region from which the cores were taken, and the pathological assessment. In the case of cancer, the report should indicate the specific grade and proportion of the tissue involved. Many laboratories supplement their reports with selected images of  the most troubling component of the tissue. In the report shown in the photo, one sees the minimal elements of a biopsy report plus a photograph of a focus of cancer from the prostatic left base. Also reported are benign tissue, atrophy, inflammation, atypical small acinar proliferation (ASAP), and high-grade prostatic intra-epithelial neoplasia (PIN). In a biopsy without cancer, the observation of ASAP and/or PIN may have implications for future cancer diagnosis, for which reason biopsy reports should routinely cite their presence. Another feature, one not seen in this example, that should routinely be reported is peri-neural invasion (PNI), a feature seen in some cancers and which has ilications regarding cance stage. 

I have been diagnosed with prostate cancer. Is it something I did?
No. Certain behaviors, which in theory can be altered, appear to be associated with cancer risk: sunbathing and skin cancer, smoking and lung cancer, and others. However, no clear link has been established between behavior and prostate cancer. While theories about behavior and prostate cancer abound, not much has been nailed down as fact. In our search for behavioral modifications that can help reduce cancer risk, dietary behavior has been examined. Among the most interesting nutrients is the mineral selenium. A number of years ago, Dr. Krongrad and his colleagues published a study in the Journal of the American Medical Association (Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis SL, Glover RA, Graham, GF, Gross EG, Krongrad A, Lesher JL Jr, Park K, Sanders BB Jr, Smith CL, Taylor JR, for the Nutritional Prevention of Cancer Study Group: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA 276:1957-1963, 1996) that demonstrated for the first time a reduced incidence of prostate cancer in men supplemented with selenium. Certain limitations in the study design require that the study now be repeated for confirmation. In any event, there is no proof that for most men selenium deficiency is a relevant problem. Furthermore, there is no proof that, once diagnosed with prostate cancer, selenium supplementation is useful. Overall, we have no obvious behavioral tools with which to prevent prostate cancer and no reason to believe that a man's specific behavior promoted the development of prostate cancer.

What is cancer grade? What is cancer stage?
All prostate cancers are minimally described by two characteristics: grade and stage. While grade and stage are correlated, they are independent ways of assessing the potential behavior of a cancer. Grade is a description of the cancer cells as they appear under a microscope and is assigned by a pathologist; the most common form of prostate cancer grading is the Gleason grading system. Stage is a description of the extent of growth of a cancer and is assessed by various means, such as physical examination and bone scans. Prostate cancer is staged commonly with the TNM system. T represents the size of the primary tumor in the prostate. N represents the involvement of lymph nodes. M represents metastasis to distant sites, e.g. bones.

How does the Gleason grading system work?
Prostate cancer is composed of cells of varying shapes. Dr. Donald Gleason characterized prostate cancer cell shape and described categories, which provide some assessment of risk of cancer stage (how extensive the cancer is) and survival. The Gleason score is a sum of the two most prevalent patterns detected by the pathologist and ranges from 2, the least aggressive, to 10, the most aggressive.

What is radical prostatectomy?
The radical prostatectomy is the complete surgical excision of the prostate, seminal vesicles, tips of the vas deferens, and, depending on oncological considerations, surrounding fat, nerves, and blood vessels. The radical prostatectomy is a standard first-line treatment for prostate cancer.

Will I need treatment after the radical prostatectomy?
The indications for additional treatment are unclear and not based in rigorous scientific study. However, contemporary standards include the use of radiation, hormones, and/or chemotherapy after radical prostatectomy in some cases. Generally speaking, the decisions to use additional treatments after radical prostatectomy are based on observations made by the pathologist of the surgical specimen. Decisions for immediate additional therapy are made in the minority of radical prostatectomy cases.