ISSUES TO CONSIDER

This section summarizes key points to consider when you’ve been diagnosed with early-stage prostate cancer. The list is by no means exhaustive, and there might be other points that you want to think about as well. The goal is to help you focus on what you need to know about each stage of disease so you can hold meaningful, regular dialogues with all members of your health care team as you find the treatment path that’s right for you.

1. The Gleason grading scale runs from 1 to 5, where 1 represents cells that are very nearly normal, and 5 represents cells that don’t look or act much like normal prostate cells at all. The Gleason score, or sum of the two most common Gleason grades (and therefore on a scale from 2 to 10), tends to predict the aggressiveness of the disease and how it will behave in your body. Tumors with higher Gleason scores, typically above 7, tend to be more aggressive.
2. The PSA level that you had before you were diagnosed with prostate cancer, known as your pre-diagnostic PSA, is often used as an indicator of how advanced your cancer was before it was detected. Usually, the higher the PSA, the more aggressive the disease. Also, the more rapidly the PSA has risen in the year prior to diagnosis and treatment, the more aggressive the disease.
3. Nomograms are simplified charts that have been specially constructed to weigh different contributing factors and to provide a single assessment of the likelihood of remaining disease-free after treatment. They can play an important role in helping to decide whether to undergo additional treatments or whether to enroll in clinical trials assessing new therapeutic regimens or agents. One useful (there are many) nomogram webpage is found through Memorial Sloan Kettering: http://www.mskcc.org/mskcc/html/10088.cfm.
4. Active surveillance might be appropriate for men who, for one reason or another, have decided not to undergo immediate surgery or radiation therapy based on his age, risk with surgery, and prostate cancer risk group. For example, immediate treatment might not make sense for men who have very slow growing or very early cancers, or in men who have a limited life expectancy (<10 years), while men who have other serious medical conditions might not be healthy enough to undergo surgery or radiation therapy.
5. During prostatectomy, the prostate and nearby seminal vesicles are removed. If performed laparoscopically or robotically, a few small incisions are made and blood loss is typically minimized. However, the procedure is technically difficult and the learning curve is steep. Surgical skill and practice with this approach is key. Ask your doctor about their surgical volume and years of experience. Currently there is little data to claim that robotic procedures offer advantages over the more traditional open radical prostatectomy, and in either case, depend on experience.
6. If you decide on surgery, the decision on whether to attempt a nerve-sparing procedure should be yours—only you can know how important it is to maintain your erectile function. But ultimately the decision on whether to perform the nerve-sparing procedure is up to the surgeon based on his or her years of experience and expert clinical judgment. If the surgeon does not feel that he or she can cure your cancer and leave the nerves intact, the nerves will not be spared.
7. The goal of radiation therapy is to kill the prostate cancer cells where they live. To accomplish this, very high doses of x-rays are delivered to the prostate, concentrated on the small clusters of tumor cells that comprise the cancer within the prostate gland. Ask your radiation doctor about the dose of radiation, how many fractions will be given, and whether testosterone lowering therapy is needed to make the radiation work better. There are different forms of external radiation, including intensity modulated radiation therapy (IMRT) and proton beam therapy. Currently there is little data to suggest that proton beam therapy offers a real advantage over more traditional radiation. Current technology is improving constantly, with the addition of fiducial markers to track the prostate in real time during the radiation therapy, 3-dimensional CT scan planning to guide the radiation dose, and hormonal therapies which can increase the chances for some men that radiation will cure them. The decision to use hormonal therapy with radiation is based on your overall health and prostate cancer risk. Some men will get 6 months of testosterone lowering therapy, and some men will get several years of this additional therapy. Typically hormonal therapies are started before radiation, continued during radiation, and completed after radiation.
8. The most common type of radiation therapy is external beam radiotherapy. Radiation oncologists and technicians use CT scans and MRIs to map out the location of the tumor cells, and x-rays are targeted to those areas. With brachytherapy, tiny metal pellets containing radioactive iodine or palladium are inserted into the prostate. Over the course of several months, the seeds give off radiation to the immediate surrounding area, killing the prostate cancer cells.
9. A number of studies have shown that the use of neoadjuvant (before and during radiation) hormone therapy can shrink larger tumors, thereby making it easier for oncologists to localize the radiation needed to kill the tumor cells, and significantly improving outcomes. This approach is now used in many institutions for men with high-grade or bulky cancers and you should ask your doctor if this is indicated for you (see above).
10. The three most significant clinical factors used to determine which initial therapy might be best are the extent of your tumor, your overall health, and your age. Psychological factors can also play an important role: only you can know how you want to deal with your disease and whether the potential side effects of one treatment outweigh those of another.
11. Technique plays an important role in determining whether urinary control and function will be maintained after surgery, and sparing the urinary sphincter is key. But pre-surgical urinary function can play an important role as well. If you’ve already experienced some hesitation and/or lack of bladder control, it will be harder for you to regain full control and function.
12. During prostatectomy, damage to the rectum is rare, and the bowel changes seen in the first few weeks following surgery are more likely the result of the body adjusting to the increased abdominal space with the loss of the prostate. Radiation therapy, however, can cause significant damage to the rectum, resulting in diarrhea or frequent stools; fecal incontinence or the inability to control bowel movements; and/or rectal bleeding. Much depends on practitioner skill, so be sure to select a doctor who possesses the experience and skill to spare the rectal tissue as much as possible.
13. Regardless of whether the nerves were spared during surgery or whether the most precise dose planning was used during radiation therapy, nearly all men will experience some erectile dysfunction for the first few months after treatment. However, within one to two years after treatment, nearly all men with intact nerves will see a substantial improvement. However, some men never quite recover the sexual function that they had prior to surgery or radiation, and require assistance with pills, shots, or implants for successful sexual intercourse.
14. Despite the best efforts of surgeons and radiation oncologists, it is nearly impossible for a man to retain his ability to father children through sexual intercourse after undergoing localized treatment for prostate cancer. For men who wish to father children after surgery or radiation therapy, the best chance for fertility is sperm banking; after thawing the frozen semen, up to 50% of sperm will regenerate and can be used for artificial insemination.
15. Dietary and lifestyle changes should be an important part of every man’s battle with prostate cancer, complementing any drug therapy, surgery, and/or radiation treatment that you might undergo. Eating healthier foods, avoiding smoking, prevention of obesity, and exercising more will help keep your body strong to help fight off your disease.

What to Consider When Your PSA Is Rising After Initial Treatment

For the majority of men, prostate cancer is treatable and curable and does not recur after local definitive therapy with surgery or radiation. However, this next section summarizes key points to consider when your PSA is rising after undergoing initial treatment. About 25-33% of men with prostate cancer will experience a recurrence of their cancer after surgery or radiation. Some of these men can still be cured with radiation after surgery, or with other local therapies after radiation. However, some men develop a form of prostate cancer that, while not curable, remains TREATABLE for a very long time.

The list below of important issues is by no means exhaustive, and there might be other points that you want to think about as well. The goal is to help you focus on what you need to know about each stage of disease so you can hold meaningful, regular dialogues with all members of your health care team as you find the treatment path that’s right for you.

1. Following surgery (radical prostatectomy), your PSA should be undetectable after about a month. That means zero PSA, not 0-4 ng/dl. However, some men will have a very low nonrising PSA after surgery, which can sometimes be related to normal prostate tissue left behind. This is uncommon, and referred to as benign regeneration. However, the most widely accepted definition of a cancer recurrence is a PSA > 0.2 ng/mL that has risen on at least two separate occasions at least two weeks apart and measured by the same lab. In the post-radiation therapy setting, the most widely accepted definition is a PSA that has risen from nadir in at least three consecutive tests conducted at least two weeks apart and measured by the same lab. Some believe that failure after radiation is not clear until the PSA has risen 2 points above its lowest value after radation. Either way, it’s important to always use the same lab for all of your PSA tests because PSA values can fluctuate somewhat from lab to lab. Defining failure after other forms of therapy like seeds or cryotherapy is more challenging, but similar to that used with external radiation.
2. One of the most important questions after surgery to ask is whether you may benefit from additional therapy like adjuvant radiation. The decision to use radiation to lower your risk of recurrence and dying from prostate cancer after surgery is based on whether the cancer has spread to your seminal vesicles, whether there were positive margins, and whether the cancer spread beyond the prostate capsule. In addition, it is important to allow time to recover your urinary function before considering radiation therapy after surgery, as radiation in this setting increases the risk of urinary strictures, leakage, and frequency. There is currently an ongoing debate about doing radiation early or waiting until the PSA has begun to rise in men with these high risk features, given these toxicities.
3. PSA velocity or PSA doubling time, both of which measure the rate at which your PSA rises, can be a very significant factor in determining is the aggressiveness of your cancer. Men with a shorter PSA doubling time or a more rapid PSA velocity after initial therapy tend to have more aggressive disease, and are therefore more likely to need more aggressive therapies. Likewise, men who have recurrence quickly after surgery (ie within 3 years) have a higher risk of aggressive disease.
4. If your PSA starts to rise after you’ve undergone prostatectomy, "salvage" radiation therapy might be a good option to explore, and has been shown to improve outcomes over time. With this approach, external beam radiation is delivered to the area immediately surrounding where the prostate was (the prostate bed), in the hopes of eradicating any remaining prostate cells that have been left behind. It is not known if hormonal therapies can improve outcomes with salvage radiation and clinical trials are ongoing to look at this. Other trials are looking at other more aggressive experimental systemic therapies in this setting.
5. With 3D conformal radiotherapy, IMRT, and brachytherapy, local tissue damage is often kept at a minimum, and surgeons at some of the larger cancer centers have been seeing improved results with “salvage” prostatectomy. But even under the best of circumstances, post-radiation surgery is a very difficult operation to perform, and few surgeons across the country perform it regularly.
6. Regular monitoring of PSA levels after primary therapy is key, as is prompt initiation of treatment upon disease recurrence. The earlier the treatment is begun, the better the likelihood of improved results.
7. Androgen deprivation therapy ("hormone therapy") is a key treatment strategy for prostate cancer that has recurred following local treatment. The goal of all hormone therapies is to stop the production and/or interfere with the effects of testosterone which fuels the growth of prostate cancer cells. However, because not all prostate cancer cells are sensitive to increases or decreases in testosterone levels, hormone therapy is a treatment for prostate cancer but does not cure the disease. The decision on starting testosterone lowering or blocking therapies is individualized, based on your PSA, the PSA doubling time, whether the cancer has spread visibly or caused symptoms, and the risks of harm with this therapy.
8. There are several approaches to blocking the secretion of testosterone including the surgical removal of the testes, drugs known as LHRH agonists, and estrogens.
9. Antiandrogens block the action of testosterone by preventing the active form of testosterone known as DHT from entering the central part of the prostate cancer cell; without DHT, the growth of prostate cancer cells is halted.
10. Testosterone is the primary male hormone, playing an important role in establishing and maintaining the typical male characteristics, such as body hair growth, muscle mass, sexual desire, and erectile function. Most men who are on hormone therapy experience at least some of the effects related to the loss of testosterone, but the degree to which you will be affected by any one drug regimen is impossible to predict. Side effects from testosterone lowering therapies include hot flashes, breast enlargement or tenderness, loss of bone mineral density and fracture, increased weight gain (especially around the midsection), higher cholesterol, a higher risk of diabetes, and a slightly higher risk of heart problems like heart attacks and chest pains. Some men complain of mood problems and depression during this time as well, and don’t be afraid to discuss these issues with your doctors. For all of these reasons, a healthy lifestyle as described in other sections, is vital to doing well with hormonal therapies over time.
11. LHRH agonists, the most commonly used drug class for hormone therapy, are given in the form of regular shots: once a month, once every three months, once every four or six months, or once per year. These long-acting drugs are injected under the skin and release the drug slowly over time. There are newer agents called LHRH antagonists that also lower testosterone and may be used.
12. Antiandrogens can be helpful in preventing the "flare" reaction associated with LHRH agonists resulting from an initial transient rise in testosterone. Their use for at least the first 4 weeks of LHRH therapy can relieve the symptoms often seen from the flare reaction, ranging from bone pain to urinary frequency or difficulty. You should ask your doctor whether continuing these pills for longer term cancer control will be beneficial to your individual case. There is some information to suggest that combination testosterone blockade and testosterone lowering therapy may be better than either one alone for long term control, but at the cost of additional side effects like breast tenderness and enlargement, cost, and hot flashes.
13. With intermittent hormone therapy, the LHRH agonist is used for six to twelve months, during which time a low PSA level is maintained. The drug is stopped until the PSA rises to a predetermined level, at which point the drug is restarted. During the "drug holidays" in between cycles, sexual function and other important quality of life measures might return. However, the clinical benefits of this approach remain unclear, and large clinical trials are currently underway to evaluate its use in this setting.
14. Deferring hormone therapy until metastatic disease can be detected might be an appropriate option for some men. In such cases, the goal would be to reserve an effective, albeit temporary, treatment option until it’s clearly needed.
15. Hormone therapy typically is effective for only a few years, but this period can range from several months to many decades. For many men who were using an antiandrogen in combination with an LHRH agonist, stopping the antiandrogen, or antiandrogen withdrawal, is the most common first step in secondary hormone therapy. Switching to a different antiandrogen might also be able to offer an extra few months of benefit, and drugs known as ketoconazole can be used to block the small amounts of testosterone produced by the adrenal glands from being released. An older estrogenic medication, DES, can also be useful when other hormonal therapies stop working. As DES can increase your risk of blood clots, using a blood thinner like Coumadin/warfarin with DES is recommended if possible. There are many trials of newer hormonal therapies in this setting and trial participation is encouraged.
16. When the PSA is rising or cancer spreading despite a low level of testosterone, prostate cancer is called castration-resistant, or hormone-refractory. Despite this name, some hormonal therapies (see above) may still work. But prostate cancer in this setting will inevitably progress and become more aggressive and resistant, and you should be prepared to discuss more aggressive treatment strategies with your doctor. This is the time when a medical oncologist, if not already involved in your care, gets involved. These doctors specialize in “systemic” treatments for prostate cancer, which is useful at this time given that your disease is typically systemic, meaning that it is not confined to only one location. Cancer cells in this situation have typically spread through the blood stream or lymphatics to other places in the body, and localized treatments are rarely helpful except in circumstances where urination becomes difficult. You should talk to your doctor about these systemic therapies, when to start chemotherapy, and clinical trials that may be available.
17. Carefully review the side effect profile of the different hormone therapy regimens, and discuss with your health care team potential ways to minimize the effects. In the end, it’s important that you not only understand the value of the therapy in the management of your prostate cancer, but also that you learn how to live your life as best as possible while fighting the disease.

What to Consider When Your PSA Is Rising During Hormone Therapy

This section summarizes key points to consider when your PSA is rising while undergoing hormone therapy. The list is by no means exhaustive, and there might be other points that you want to think about as well. The goal is to help you focus on what you need to know about each stage of disease so you can hold meaningful, regular dialogues with all members of your health care team as you find the treatment path that’s right for you.

1. A rising PSA during hormone therapy doesn’t mean you’re out of options—it means you need to consider the use of other systemic therapies such as chemotherapy, alternative hormonal medications, or agents that target the spread of prostate cancer (metastasis). Some of these options may be available through clinical trials. This field is constantly changing with new drug and cancer vaccine approvals expected in 2010-11, so consulting with your doctors about some of these newer therapies is encouraged.
2. When your cancer is progressing despite a low level of testosterone in the blood (a blood test can check this, and it should be less than 50 ng/dl while on testosterone lowering therapies), we term this state castration-resistant, or androgen-independent, or hormone-refractory prostate cancer. However, some hormonal therapies can still work in this setting, including bicalutamide, flutamide, nilutamide, ketoconazole, steroids, and DES. Your doctor should decide if these are right for you based on the risks and benefit of each of these medications. Bicalutamide, flutamide, and nilutamide work by blocking testosterone’s receptor, while ketoconazole lowers testosterone even further by reducing the adrenal gland’s production of testosterone. DES is an estrogen that can lower testosterone and has anti-cancer activity. Finally, steroids can be sometimes useful by themselves to control pain and reduce the PSA for a period of time. In general, however, most of these medications only work for a relatively short period of time, on the order of 3-5 months on average, so planning for the future and other treatments remains important.
3. The primary goal of chemotherapy is to stop the cancer cells from dividing and the cancer cells from growing. But when we look at whether a drug is working, there are generally two levels of effectiveness—whether a drug is palliative, meaning whether it can alleviate symptoms, and whether it can affect the cancer cell growth significantly enough to prolong life. Sometimes chemotherapy can do both of these things, and how much chemotherapy will benefit a man is very individualized based on their individual profile. It is important to see a medical oncologist early in your disease course so that these treatment options can be considered in a timely manner.
4. The benefits of chemotherapy in prostate cancer were only first realized recently: estramustine (Emcyt) has been around for several decades as a palliative therapy for men with prostate cancer; mitoxantrone (Novantrone) was approved by the FDA in 1996 when it was shown to provide palliative benefit to men with advanced prostate cancer; docetaxel (Taxotere) was approved in 2004 when it was shown to prolong the lives of the men who took it and relieved symptoms better than mitoxantrone.
5. Although all chemotherapy drugs are designed to slow or stop the growth of cancer cells, each one tends to work in a slightly different way. However, we do not know if combining chemotherapies provides a greater benefit to men with prostate cancer and this may increase toxicities. Currently, the standard of care is to treat with one chemotherapy first (usually docetaxel and prednisone), followed by additional therapies when docetaxel stops working. There are many ongoing clinical trials looking at adding experimental medications to docetaxel to make docetaxel work better and prolong life and quality of life. We encourage you to discuss whether a clinical trial is right for you with your doctors.
6. Pay close attention to your reactions to the different chemotherapy drugs. You’re the only one who really knows your own body, so you’re the only one who can know whether you are able to tolerate a particular treatment regimen. Typically, low dose prednisone is given with docetaxel and mitoxantrone to help with the tolerability of chemotherapy. However, prednisone has several side effects as well that you should be aware of, including sleep problems, increased appetite and weight, thinning of the skin, upset stomach, accelerated bone loss and fracture risk, and infections.
7. Don’t be too tough or “macho.” There are plenty of drugs available to help ward off (prevent) or treat the different side effects of chemotherapy, especially to prevent nausea and vomiting.
8. Focus on yourself. It doesn’t matter what you do, as long as it can help you relieve stress and can help you with the most important part of your cancer treatment—getting well. Having a strong social support network through family and friends will help with your ability to fight your cancer. Prostate cancer support groups around the country can also provide this needed support. Ask your doctor about one in your area.
9. Prostate cancer cells that have spread beyond the prostate seem to prefer bone tissue and tend to migrate there after escaping the pelvic region. Once the cells settle in, they’re known as prostate cancer bone metastases. Unlike bone cancer, which originates in the bone, prostate cancer bone metastases are actually collections of prostate cancer cells that happen to be sitting within the bones.
10. When prostate cancer cells settle in the bones, they interact with the bone cells, causing new bone cells to grow and causing the bone tissue to break down. The dye-like material that’s injected during a bone scan highlights areas of bone metabolism or activity—areas where bone tissue is changing more rapidly than it normally would in a healthy adult male.
11. Men who experience pain from a bone metastasis will often be treated with radiation targeted directly to the metastasis or with radiation-emitting drugs that settle in the metastasis after being injected through a vein. The radiation will kill the prostate cancer cells in the metastasis and thereby relieve the pain.
12. Bisphosphonates are drugs that are designed to help reset the balance in the bone between bone growth and bone destruction which is disrupted by the prostate cancer bone metastases. Zoledronic acid (Zometa) is a bisphosphonate given intravenously that can delay the onset of complications associated with prostate cancer bone metastases and relieve pain. It is typically given once every three weeks as a 15-minute infusion. Less frequent schedules are sometimes used as well depending on your individual circumstance and risk. There are some risks with zoledronic acid including something called osteonecrosis of the bone (ONJ) that can occur after deep dental procedures and extractions or sometimes spontaneously. This results in sometimes jaw pain and poor healing of your teeth.
13. As the bones in the spine weaken, they can collapse one of top of the other, compressing the spinal cord and the nerves that run out from it. Spinal cord compression associated with metastatic prostate cancer can cause serious problems if not managed immediately, so be sure to tell your doctors about any new pain, weakness, or changes in bowel habits, any of which can result from spinal cord compression. Steroids and radiation are used if this occurs.
14. Cancer can be painful, and there’s no benefit in acting stoic and pretending it doesn’t affect you. There are plenty of very effective pain medications available, and using them will allow you to feel better and stay stronger.
15. Don’t assume that you can’t get pain relief unless you’re completely doped up. Some very simple and easy to take oral medications might be enough to ease your pain without causing you to lose your focus and ability to work and function.
16. Don’t worry about becoming addicted to pain medication. Taking pain medications so that you can spend your days feeling healthier and stronger is the opposite of addictive behavior. However, both physical dependence and tolerance are possible as your body starts to get used to the drugs, so you and your doctors should take them into consideration as you start and stop different pain medications.
17. Consider enrolling in a clinical trial of an experimental new treatment or regimen. Clinical trials are the only way that new and better treatments will be developed and tested appropriately. Clinical trials are the reason that we have effective therapies for prostate cancer today, and there are many more effective therapies out there to explore.

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