A918: Prostate: adenocarcinoma

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1 A918: Prostate: adenocarcinoma General facts of prostate cancer The prostate is about the size of a walnut. It is just below the bladder and in front of the rectum. The tube that carries urine (the urethra) runs through the prostate. The prostate contains cells that make some of the seminal fluid. This fluid protects and nourishes the sperm. Male hormones cause the prostate gland to develop in the fetus. The prostate keeps on growing as a boy grows to manhood. If male hormones are removed, the prostate gland will not grow to full size, or it could shrink. Most of the time, prostate cancer grows very slowly. Autopsy studies show that many elderly men who died of other diseases also had prostate cancer that neither they nor their doctor were aware of. But sometimes prostate cancer can grow and spread quickly. Even with the latest methods, it is hard to tell which prostate cancers will grow slowly and which will grow quickly. Some doctors believe that prostate cancer begins with very small changes in the size and shape of the prostate gland cells. These changes are known as PIN (prostatic intraepithelial neoplasia). These changes are grouped as either low-grade (almost normal) or In high-grade PIN a higher chance that there are cancer cells in the prostate. Treatment Surgery Surgery is a common form of treatment for men with prostate cancer. Surgery attempts to cure prostate cancer by removing the entire prostate and getting all of the cancer out of the body. An attempt at a surgical cure for prostate cancer is usually done with early stage prostate cancers, but sometimes surgery will be used to relieve symptoms in advanced stage prostate cancers. Surgery for prostate cancer is generally felt to be equivalent to radiation for prostate cancer in terms of survival, especially in early stage, low to intermediate grade cancers. The decision to have surgery versus radiation is often made on the basis of the patient's age and health status; the two different approaches have different side effect profiles depending on the patient's age. The most common surgical procedure for prostate cancer is known as a radical prostatectomy. Radical prostatectomy means that the entire prostate gland is removed from around the tube that connects the bladder to the penis (the urethra). This surgery can be done in two different ways, the retropubic approach and the perineal approach. The retropubic approach means that incision in in the are and have them quickly examined by a pathologist for signs of cancer. If the nodes have cancer, then the surgeon will not to proceed with the operation. This is the major reason a retropubic approach is used in most surgeries today.

2 Radical prostatectomies are very safe surgeries with few life threatening complications; however, there is a significant risk for other side effects. Both urinary incontinence (not being able to hold in urine) and impotence (inability to achieve and maintain an erection) are commonly associated with this procedure. The risk for having either of these side effects increases with age; this is why younger men are often recommended to have surgery while older men are recommended to have radiation. Radiotherapy Prostate cancer commonly is treated with radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation therapy is another option besides surgery for early stage prostate cancer; and when advanced stage prostate cancer needs to be treated, it is usually done with radiation therapy. Radiation helps avoid surgery in patients who are too ill to risk having anaesthesia. Radiation is usually offered to older patients in the case of early stage prostate cancer because of its side effect profile is less than surgery in the elderly. Radiation can have impotence rates similar to surgery, but the risk of urinary incontinence is very low. Impotence develops months to years after the radiation treatment, unlike with surgery, which tends to have the side effects occur immediately. Other side effects from radiation include bladder irritation, which can cause urinary frequency and urgency as well as bladder pain, and diarrhea or rectal bleeding. Radiation oncologist tries they are in such close proximity to the prostate. Radiation therapy for prostate cancer either comes from an external source (external beam radiation) or an internal source where small radioactive seeds are implanted into the patient's prostate (brachytherapy). External beam radiation therapy requires patients to come in 5 days a week for up 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Brachytherapy is done as a one-time insertion, in the operating room. Brachytherapy cannot be done in all patients and is usually reserved for early stage prostate cancers. Your radiation oncologist can answer questions about the utility, process, and side effects of both of these types of radiation therapy in your particular case. Hormonal Therapy Both normal prostate tissue and prostate cancers depend on male sex hormones, called androgens, to grow and replicate. Testosterone is an androgen very important to the prostate gland. Men make androgens in their testicles. One of the ways to treat prostate cancer is to remove androgens from the body, thus making the cancer shrink and then grow more slowly. There are a few different ways to remove androgens: you can remove a man's testicles (called an orchiectomy), you can give a man drugs that block the production of androgens (called LHRH agonists), you can give a man drugs that block androgen receptors (called anti-androgens) or you can give a man estrogens. Different methods of deceasing androgens are often used in the same patient: using LHRH agonists with anti-androgens can achieve what is known as a total androgen blockade. Hormone therapy can also be used in conjunction with other treatments, especially in the case of advanced stage prostate cancer being treated with radiation therapy. In that case, hormonal therapy is often given before the radiation and this is known as neoadjuvant hormonal therapy. Another use for hormones is in patients who present with metastatic disease. After a while, all prostate cancers will become resistant to hormonal therapy. However, this often takes many years and hormonal therapy can buy a lot of time in patients with extensive disease or patients who choose not to undergo surgery or radiation.

3 Chemotherapy Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Chemotherapy is prescribed by medical oncologists, who are experts at choosing appropriate regimens for particular patients. Chemotherapy for prostate cancer is generally only reserved for very advanced cancers that are no longer responsive to hormonal therapy. There are a number of chemotherapy drugs that can be used for prostate cancer, and they are often used in combinations. A common chemotherapy regimen is Mitoxantrone with Coritcosteroids; and other regimens that are becoming increasingly popular use a drug called Estramustane with drugs called Taxanes. The use of chemotherapy in prostate cancer is currently being studied and men who get chemotherapy are encouraged to talk to their doctors about experimental trials. Cryosurgery Cryosurgery is a somewhat experimental approach to treating prostate cancer whereby probes with liquid nitrogen are implanted into the prostate and then the tissue is frozen. This freezing kills the cancer cells, and it can be repeated multiple times if needed. However, data to date has shown that cryosurgery is not as effective as radiation and surgery for treating prostate cancer. Cryosurgery also has a variety of side effects including urinary incontinence and impotence. Watchful Waiting Some patients choose to receive no therapy for their prostate cancer in the hopes that it will grow very slowly. By avoiding any therapy, they avoid the side effects that come along with surgery, radiation, or hormones. Watchful waiting is appropriate for older men with small, low-grade tumors, and slowly rising PSAs, and multiple other medical pro Watchful waiting can be considered in patients who have a life expectancy less than 10 years as long as the cancer isn't large or of a high grade. Men who choose to undergo watchful waiting should have PSAs and digital rectal exams done every 3-6 months, and need to be re-biopsied at some point to make sure the grade hasn't become less favorable. However, it is never really clear what change in clinical status should institute treatment. Also, if the tumor has progressed, they may no longer be eligible for curative therapy. Follow-up testing

4 A918: Prostate: adenocarcinoma The American Cancer Society All About Prostate Cancer Overview Barry MJ (2001). Clinical practice. Prostate-specific-antigen testing for early diagnosis of Carducci MA (2001). NCCN Prostate Cancer practice Guidelines Panel. NCCN: New Duchesne G M. Radiation for prostate cancer Lancet Oncology. 2(2):73-81 Hellerstedt BA and Pienta KJ. The current state of hormonal therapy for prostate cancer. Jemal, A. et. al (2002). Cancer Statistics, Ca: a Cancer Journal for Clinicians 52 Montironi R et. al (1999). Prostate cancer prevention: review of target populations, National Cancer Institute. What You Need To Know About Prostate Cancer. Rubin, P. and Williams, J.P., (Eds): Clinical Oncology: A Multidisciplinary Approach for

5 Primary tumor (T) Staging of prostate cancer TX: Primary tumor cannot be assessed T0: No evidence of primary tumor T1: Clinically inapparent tumor not palpable nor visible by imaging T1a: Tumor incidental histologic finding in 5% or less of tissue resected (in prostatectomy) T1b: Tumor incidental histologic finding in more than 5% of tissue resected T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA) T2: Tumor confined within prostate T2a: Tumor involves one-half of 1 lobe or less T2b: Tumor involves more than one-half of 1 lobe but not both lobes T2c: Tumor involves both lobes T3: Tumor extends through the prostate capsule T3a: Extracapsular extension (unilateral or bilateral) T3b: Tumor invades seminal vesicle(s) T4: Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles,and/or pelvic wall Regional lymph nodes (N) NX: Regional lymph nodes were not assessed N0: No regional lymph node metastasis (lymph nodes confined to the true pelvis) N1: Metastasis in regional lymph node(s) Distant metastasis (M) MX: Distant metastasis cannot be assessed (not evaluated by any modality) M0: No distant metastasis M1: Distant metastasis M1a: Nonregional lymph node(s) M1b: Bone(s) M1c: Other site(s) with or without bone disease Stage I T1a, N0, M0, G1 Stage II T1a, N0, M0, G2, 3-4 T1b, N0, M0, any G T1c, N0, M0, any G T1, N0, M0, any G T2, N0, M0, any G Stage III T3, N0, M0, any G Stage IV T4, N0, M0, any G Any T, N1, M0, any G Any T, any N, M1, any G Histopathologic grade (G) GX: Grade cannot be assessed G1: Well differentiated (slight anaplasia) (Gleason 2-4) G2: Moderately differentiated (moderate anaplasia) (Gleason 5-6) G3-4: Poorly differentiated or undifferentiated (marked anaplasia) (Gleason 7-10) Gleason score: In general, degree of tumor differentiation and abnormality of histologic growth pattern directly correlate with likelihood of metastases and with death. Because of marked variability in tumor differentiation from one microscopic field to another, many pathologists will report the range of differentiation among the malignant cells that are present in a biopsy, also known as Gleason score.

6 Stage grouping Memory Aid: Stage I corresponds to T1a, G1 only. Stage II corresponds to T2 plus any the remaining T1 subclasses (T1b, T1c) Stage III corresponds to T3 Stage IV corresponds to T4 or N, or M. References 1. Prostate. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp

7 A918: prostate : adenocarcinoma Lot. No : N1 N2 T1 N1 Fig2. RT-PCR for GAP3DH Sample : Serial 10 sections of 10micrometer slice Fig 1. Scanned images for H&E stained slides. T1 N1 RNA conc. (ng/ul) / Pathology or other information: AGE: 51 Sex: Male Stage: T2bN0M0 Pathology: 1.Prostate, prostatectomy: Adenocarcinoma (Gleason's score: 3+4:7) 1) involving both lobes of peripheral and transitional zone without extracapsular extension (T2c by TNM stage and B2 by American staging system) and extensive perineural invasion. 2) lymph nodes, external iliac, right(0/3) and left(0/5): Free of tumor metastasis in all 8 nodes.