Cancer Consultation 11404 West Dodge Rd, Ste 650 Omaha, NE 68154 (402) 963-4112 (888)WEB-OPIN (932-6746) Patient: John Doe July 1, 2010 Referral MD: John Smith, MD MRN #<10-00000-01 CancerOpinions MD: Luke Nordquist, M.D., F.A.C.P Zip Code: 68111 Cancer Type: Prostate Cancer Metastatic: Resistant to Hormones 1. REASON FOR CANCER CONSULTATION FOR John Doe : I have prostate cancer which has now spread to my spine and the hormone treatments are no longer working because my PSA is rising. 2. SUMMARY OF CANCER HISTORY FOR John Doe: Mr. Doe is a 68 year old gentleman with a history of Gleason 7 (4+3) prostate cancer. He was diagnosed in May of 2004. His initial PSA was 14ng/ml. A biopsy demonstrated bilateral Gleason 7 prostate cancer involving 5 of 12 cores (45% of the submitted tissue was involved with prostate cancer). His staging workup demonstrated no evidence of metastatic disease on bone scan and CT scan of the abdomen & pelvis. He underwent robotic prostatectomy in June 2004. Pathology confirmed Gleason 7 (4+3) cancer, there was no extraprostatic extension, all lymph nodes were negative for cancer, and all surgical margins were negative. His PSA did not nadir to undetectable and the patient was reluctant to consider salvage radiation. He was started on testosterone suppressive therapy with every 3 month Lupron and daily Casodex 50mg in August 2004. His PSA responded to hormone treatments until December 2009 when his PSA started to rise. Repeat scans showed no metastatic disease. His treatment was changed to Nilandron 150mg daily and he continued the Lupron. His PSA again responded until May 2010. Repeat scans in June 2010 then showed 2 new sites of metastatic disease in his right humerus (arm bone) and his sacrum. CT scans did not demonstrate any enlarged lymph nodes. The patient remains without symptoms and carries out normal daily activities. I was asked to review his records and provide treatment recommendations.
3. THE BASICS ABOUT CANCER CANCER IN GENERAL What is a Cancer? Cells in the body normally divide from one cell into two cells, and so on. If however, any cell makes a mistake, called a mutation, during the dividing of the cells, the mutated cell starts to replicate or clone itself in an uncontrollable manner, this becomes a cancer. The type of cancer it turns into is determined by which cell in the body makes the mistake. If it was a breast cell it turns into a breast cancer, if it was a white blood cell it turns into a leukemia, etc. What makes a cancer deadly compared to a benign (non-cancerous) tumor is the fact that cancers have the ability to grow and invade the surrounding tissue or structures. This ability to invade tissue allows it to spread to vital organs, making it potentially deadly. When cancers invade blood vessels the cancer gains access to the body s highway system and can spread to organs such as the liver, lungs, brain, and bone. When a cancer spreads from its original site to another site in the body it does not change the cancer type. For example, if a breast cancer spread to the liver and bones, it is still breast cancer but in the liver and bones. The cancer can also invade into a part of your body s immune system called the lymph nodes, which are scattered throughout our bodies and connected by lymph vessels. This spreading of a cancer throughout the body is called metastatic cancer. BASICS OF CANCER TREATMENT There are 3 main tools available to fight your cancer: Surgery, Radiation, & Chemotherapy. In general, surgery and radiation are used to treat a localized cancer in one area. Examples would be a cancer confined to the prostate or a cancerous lump in the breast. When the cancer is localized to one spot, it is potentially curable with surgery and/or radiation as the cancer has not metastasized. Chemotherapy includes many different types of drugs that may be given through a vein, by an injection, or a pill, including newer targeted treatments and hormonal treatments used to treat cancers such as breast or prostate cancer. Chemotherapy gets into the body and goes nearly everywhere the cancer goes. It is mainly used to shrink or control a cancer but in particular cancers the chemotherapy is effective enough to eradicate all of the cancer cells for cure as can be the case with testicular cancer or some lymphomas. Older chemotherapy worked primarily by attempting to stop any cell from dividing. It didn t differentiate between normal or cancer cells, but since cancer cells are more actively dividing than most normal cells, the chemotherapy was able to effect the growth of cancers. Newer treatments called targeted therapies attack targets that are found on cancer cells but tend not to be on normal cells so these drugs may be more effective with fewer side effects. WHY DO CANCERS RECUR? It takes approximately 1 billion cancer cells to make a 1cm tumor (Approximately 1/3 inch in size). A cancer needs to be about this size to reliably show up on cancer detection scans such as a CT scan, bone scan, MRI, PET scan, etc. So when a cancer appears to be confined to its original site of origin and it is surgically removed, a majority of the time the
surgeon will get it all and you would be cured, but if any cells are left behind undetected, these cancer cells may eventually grow and show up as a recurrence. Occasionally, chemotherapy given before or after surgery or radiation is able to eradicate these microscopic cells and increase your chance of cure. 4. THE BASICS ABOUT PROSTATE CANCER THE PROSTATE GLAND The prostate is a walnut-sized gland in your pelvis that sits just below the bladder and in front of the rectum. The purpose of the prostate gland is to store a liquid that nourishes sperm so the gland is really needed only for reproduction purposes. The prostate can often affect the urine stream because the gland encircles the urethra tube that drains the urine from the bladder through the penis. So prostate cancer, or an enlarged prostate can pinch down on the tube making urination difficult, weak, or frequent. PROSTATE CANCER Prostate cancer happens to be the most frequent cancer diagnosed in American men accounting for 25% of all new cancers diagnosed in men in 2009. The good news is that more than 90% of these prostate cancers will be detected when the cancer is confined to the prostate gland. Nearly all of these men will be alive from their cancer 5 years later and 2/3 of these men may be cured with appropriate treatment. The other 1/3 of the men, that initially appear curable, will have microscopic cancer cells left behind outside of the prostate but too small to see and eventually will cause a recurrence. Advanced computer tools called nomograms can be used to give more accurate individual patient predictions of cure for the different treatment options to help the patient in making the most appropriate treatment decision. Despite the majority of men with prostate cancer doing very well over time, it can be deadly and is the 2 nd leading cause of cancer death in American men behind lung cancer. There are several very important factors about your prostate cancer that your physician will use to help determine the aggressiveness of your disease, the extent of your disease, and which treatments are necessary or appropriate. Minimally, these include your Gleason score, PSA blood level, testosterone level, bone scan and CT scan results. So why is it that prostate cancer, in some men grows very slowly and may not ever cause symptoms or problems; and in other men the prostate cancer spreads rapidly, causing pain, fatigue, and ultimately leading to death? Part of the answer lies in the level of aggressiveness of the prostate cancer called the Gleason Score. After your biopsy or surgery you should be assigned a Gleason score between 2-10. This score does not tend to change over time. Knowing the Gleason score helps your cancer doctor determine which treatment is most appropriate for you. A Gleason score less than or equal to 6 is the least aggressive cancer. Gleason 7 s are intermediate aggressive cancers, and Gleason 8-10 are the most aggressive cancers.
95% of prostate cancers are a type of cancer called an adenocarcinoma (by definition adeno is Greek for the word gland & carcinoma is medical term for cancer, so cancer of a gland ). Adenocarcinomas of the prostate gland produce PSA (prostate specific antigen), which is not the cancer but rather a protein made only by the prostate gland and prostate cancer cells. An elevated PSA is often the reason why a man undergoes a prostate biopsy. Although not perfect, the PSA is currently the best blood test available for monitoring the cancer and its response to treatments. When prostate cancers do metastasize they tend to predominantly spread to lymph nodes in the abdomen and pelvis and to bones. Rarely, a prostate cancer may be a different type other than an adenocarcinoma, such as a neuroendocrine cancer of the prostate. Neuroendocrine prostate cancers are more aggressive and tend to spread to many places in the body such as the liver and lungs and may not make PSA. Standard prostate cancer treatments are usually less effective for this rare type. To evaluate the extent of your disease and knowing that prostate cancers tend to only spread to lymph nodes in the abdomen and pelvis and bones, your doctor will typically order a bone scan to evaluate for spread to bones and a CT scan to evaluate for lymph nodes. As mentioned above these tests may not detect very small deposits of cancer. Once your doctor has these results he will assign your cancer stage. The stage defines your extent of your disease. There are various staging systems used for different cancers. For prostate cancer, I find the most useful staging system is the Clinical States Model (See Diagram 1 for a modified version of the Clinical States Model). This staging system allows your doctor to track your cancer as it progresses over time and defines goals and treatment options for each clinical state (the 4 black boxes below). A patient stays in one box as long as his cancer has not progressed to the next box. Once you are diagnosed with prostate cancer, there are 4 clinical states that you could encounter: Diagram 1 Modified Clinical States Model Localized Cancer Rising PSA Responsive to Hormone Therapy (Microscopic) Disease Metastatic Cancer Responsive to Hormone Therapy Metastatic Cancer Resistant to Hormone Therapy 1) Localized Cancer: The cancer appears confined to the prostate gland and has not spread. The treatment options include potentially curative treatments with surgery or
radiation or if you are older or have a less aggressive cancer, you may decide to opt for non-curative hormone treatment to control the cancer or possibly even no treatment at all ( watchful waiting ). If a curative option was chosen and no cancer cells were left behind, we would expect your PSA to go to undetectable levels after surgery and very near undetectable levels after radiation, since only 2 things in the body make PSA, the prostate gland and cancer cells and they should all be out of the body. As long as the PSA stays at those levels you would be considered cured and would never move to the next clinical states box. However, if at anytime the PSA rises after surgery or radiation that typically indicates that there were cancer cells left behind causing the PSA to rise. You then move to the 2 nd clinical state: 2) Rising PSA: Responsive to Hormone Therapy: The PSA rise indicates that the cancer is present, but the bone and CT scans do not detect the small amount of cancer present. Once a patient moves to the Rising PSA stage, the cancer can occasionally still be cured with salvage treatments, however the vast majority of men are at this point considered non-curable but with appropriate treatment, they can be treated and controlled for many years. The standard treatment to control the cancer at this state involves drugs that shut down the male hormone testosterone, which is the main fuel for the cancer. These drugs are referred to as hormone therapy. Patients remain in this state and can often respond to hormone treatments for many years. When the cancer finally shows up on the bone scan or CT scan the patient moves to the next clinical state. 3) Metastatic Cancer: Responsive to Hormone Therapy: The standard treatment for this clinical state remains hormone therapies to shut down or block the testosterone levels, thus minimizing the cancer s fuel source. There are several different hormone therapies that work differently from one another and you may get benefit from one treatment even if another hormone treatment already failed. When the hormone therapies fail to control the PSA or prevent significant progression of the cancer on the bone or CT scans, then you move to the final Clinical State. 4) Metastatic Cancer: Resistant to Hormone Therapy: At this point treatment standard treatment changes to a chemotherapy drug called docetaxel (Taxotere ). This is currently, the only chemotherapy that has been shown to extend life with advance prostate cancer. It is given through a vein every 3 weeks. Another more recent FDA approved drug is Provenge which is a personalized vaccine that has shown to make men with advanced prostate cancer live longer. There is also extensive research ongoing to develop newer more effective treatments for this cancer, so participating in a clinical trial (research study) should be considered throughout the course of your cancer, but especially when no standard options are available. A WORD ON BONE METASTASES Bones (ribs, spine, pelvis, arm and leg bones) are the most common site for prostate cancer metastases. The bone scan is the standard test to evaluate the extent of cancer in the
bones. For the most part, the cancer treatment does not change when the bones are involved and treatments such as hormones or chemotherapy work on prostate cancer in the bones just as they would for other parts of the body. However, occasionally, a symptomatic bone metastasis causing pain may need additional treatments such as radiation to treat the pain. You may also receive a drug called zolendronic acid (Zometa ) which has been shown to slow the cancer progression in the bones, decrease bone pain, and help prevent bones breaking from the cancer in men with prostate cancer resistant to hormone treatments. If you have uncontrolled pain in multiple areas, you may benefit from samarium (Quadramet ) which is a drug that is indicated for bone pain caused from metastatic prostate cancer. Finally, there are rare emergencies when dealing with prostate cancer, but one true emergency is cord compression. Cord compression is the prostate cancer spreading from the bones of your spine and compressing on your spinal cord. If not promptly treated with steroids followed by surgery or radiation, this can lead to permanent paralysis. Early cord compression can be detected with an MRI. This background information was intended to provide you with a simplistic overview of your type of cancer. For more detailed educational material about your type of cancer, we suggest the American Society of Clinical Oncology website: http://www.cancer.net/patient/cancer+types 5. CANCER TREATMENT OPTIONS FOR John Doe: Treatment options for metastatic prostate cancer depend primarily on whether the cancer is still responsive to hormone treatments and the extent of disease and symptoms you are experiencing. Hormones used to lower the testosterone levels thus minimizing the fuel source for the cancer remain the standard treatment for metastatic prostate cancer. A common goal is to achieve a testosterone level less than 50 with these treatments. There are different hormone drugs that work differently to lower the testosterone levels. There are shots (Lupron, Zoladex, Trelstar, Eligard, etc) that all work similarly, but made by many different manufacturers. These shots are given every few months to shut down the main source of testosterone in the testicles. A pill called ketoconazole works to shut down a smaller source of testosterone that is produced in the adrenal glands which sit just above your kidneys. There are other pills (Casodex, Nilandron, and Eulexin ) that don t lower the testosterone levels but work by blocking the testosterone from fueling the cancer cells. Despite the failure of one or even 2 of these treatments, response from additional hormone treatments may still be possible. Given that at this point the cancer is not curable, it is important to not prematurely eliminate any of these drugs from your treatments options. If you have metastatic disease and minimal symptoms, the newly approved personalized Provenge vaccine could improve the length of your survival but may not affect your PSA or slow the cancer progression. If you have extensive disease causing pain or other significant symptoms, a more aggressive approach of treatment with Taxotere chemotherapy should be considered. Once your prostate cancer has spread to the bones and the hormone treatments are no longer working, you should receive Zometa. This is commonly given by
the vein monthly. You should also consider clinical trials if they are available and you are eligible. Two very promising treatments being researched for metastatic prostate cancer are MDV3100 and abiraterone. Please see the attached list of current research studies which may be available to you within a 500 mile radius of your home. (premium level consult only) 6. CURRENT RECOMMENDATIONS FOR John Doe : After thorough review of your cancer records, I would recommend continuing the Lupron injections and the monthly Zometa. I would want to be notified if you were to have any dental procedures done given the risk of chronic infection in the mouth after receiving Zometa. I would discontinue the Nilandron. One could consider giving every 3 week Taxotere as your next treatment, however, given that you are currently not experiencing any symptoms, although not wrong, may be a little aggressive at this time. Taxotere could be reserved for when you develop more symptoms such as bone pain or significant fatigue or weight loss. Given that you are currently not experiencing symptoms, I feel you would be a good candidate for the Provenge vaccine. You could contact Dendreon Oncall (1-877-336-3736) to find your closest Provenge treatment center. A final option would be a trial of ketoconazole 400mg 3 times per day given with hydrocortisone replacement, however this requires up to 8 pills per day given with an acidic drink (ie cola, orange juice, etc) and I wouldn t expect a dramatic treatment response at this point. I would recommend repeating your bone and CT scans in 3 months. Thank you for allowing me the opportunity to participate in your cancer care. Luke Nordquist, MD, FACP Urologic Cancer Specialist CancerOpinions.com makes every effort to produce a second opinion that provides you with a better understanding of your type of cancer and the treatment options available to you. We also realize that cancers and treatments can be complicated and difficult to understand. If after reviewing your report you still have questions regarding its content, talk with your referring physician or have your referring physician contact us at admin@canceropinions.com or 1-888-WEB-OPIN (932-6746). The Services provided by CancerOpinions.com are in no way intended or designed to replace a full in-person medical evaluation or examination. CancerOpinions.com is simply facilitating a second-opinion consult between your physician and CancerOpinion.com s independent physician specialists. Any recommendations made by CancerOpinions.com are expected to be thoroughly discussed with your personal physician or specialist. If you decide to implement a recommendation or recommendations from CancerOpinions.com, it is expected that such implementation shall be in compliance with all applicable laws and regulations, and overseen by a properly trained and licensed physician in accordance with standard United States medical practice guidelines, the standards of the physician s specialty, and the standards imposed by the Code of Medical Ethics of the American Medical Association.