Other Excerpts

FUEL UP YOUR DEFENSE

One of the best pieces of advice that I received during my medical training was to develop a comfort level with being able to admit when I didn’t know something. After completing four years of college, four years of medical school, three to six years of residency, then often a specialty fellowship for another year or two, many doctors find this advice very difficult to follow. While I’m confident in my knowledge about various aspects of cancer, I’m admittedly no expert in the field of nutrition. In fact, I learned more about nutrition during my extracurricular activities than I did throughout my entire medical training.

Over the past decade, I decided to make a transition from aging soccer player to long-distance runner and triathlete. Before long, my goals in the field of endurance sports became loftier (and longer). When making the leap from shorter-distance races to marathons and long-distance triathlons, the importance of nutrition suddenly became much more meaningful in my life. At the same time, I began to delve deeper into the impact of nutrition on my patients.

In my humble opinion, most medical schools don’t provide future doctors enough formal instruction about the impact of nutrition on general health. Specifically, there’s little discussion about the role that diet plays in minimizing the risk of chronic diseases, including life-threatening illnesses like cancer. Readers who have primary doctors that are knowledgeable about nutrition and are able to share that knowledge should consider themselves very fortunate.

Most unfortunately, however, there’s a vast amount of misinformation splattered throughout lots of Web sites and in print about foods to eat for cancer prevention or risk reduction. What should you believe? Which sources are credible? Perhaps most importantly, where’s the data?! Plenty of people make grand claims about the power of various food products, herbal mixtures, and supplements to improve health. Sadly, the majority of these products either haven’t been studied or they’ve been studied but found to have no proven protective effect against cancer. Modern snake oil salesmen still prey on people’s fears, hopes, and misconceptions. Some sound very convincing and authoritative with claims of cancer prevention. Buyers beware!

Other lower life forms market their products to patients who already have a cancer diagnosis. These patients may be struggling through side effects of cancer treatments that have been proven effective, including surgery, radiation therapy, chemotherapy, or other newer biologic therapies. During these difficult times, less-educated patients are particularly vulnerable to suggestions of “all natural” miracle cures. As one of my old bosses liked to say, “Show me the data!”

Many effective anti-cancer medications and other medical treatments have been “discovered” thanks to naturally occurring plant or animal products. Undoubtedly, researchers and scientists will continue to find gifts in nature with potent medicinal qualities. However, if and/or when there’s a magic pill or single food product that guarantees cancer prevention or cure, rest assured that the scientific and medical professionals will be thrilled! That information will be widely and rapidly available. Until that time, it’s critical to have a basic understanding of the often complex relationship between cancer risk and nutrition.

Throughout the remainder of this chapter, the impact of dietary or nutritional modification on the risk of developing the most common cancers will be discussed. While a tremendous amount of research has been done regarding the optimal nutrition for patients who already have cancer, the discussion here is limited to reducing risk of a cancer diagnosis in healthy patients. There’s also a tremendous amount of existing information about the impact of dietary factors on growth of cancer cells in the laboratory. However, as is the case with many promising new medications, what may look like a home run in the Petri dish or laboratory rodent is frequently a foul ball in the human body. For this reason, the review in this chapter focuses on major studies that have evaluated cancer risk reduction in real people; thousands and thousands of real people!

TAKE THE BALL BY THE HORNS

No, the title of this chapter doesn’t contain a typo. My wife is the queen of the mixed metaphor. On more than a few occasions, she’s had our friends in stitches with her uncanny ability to mix words and phrases. However, “Take the Ball by the Horns” wasn’t a Jill Maguire original. It’s my way of conveying that people who truly care about reducing their risk of cancer need to take an active, maybe even aggressive role in the process. For many, it may not mean literally taking a ball out to play a regular game of soccer or basketball. Regular walking, running, biking, swimming, or other vigorous physical activity will serve the purpose. Many people are able to get that type of activity while they work. Most of us, however, need to carve out leisure time for the purpose. As with many aspects of life, if it’s important enough, we’ll find the time!

Can a book about health improvement truly be complete without a chapter on exercise? Most folks love it or hate it. They find it a source of pleasure and stress relief or dread it like a form of torture. Some guys look forward to their weekend ballgame, and may even prepare for it by running and lifting weights two or three days during the week. Others look forward to sitting on the couch to watch a ballgame. Some women look forward to their morning run as the highlight of their day, a time when they feel most awake and alive. Others look forward to sleeping that extra hour, too exhausted to even think about regular exercise. Regardless of one’s emotions about exercise, however, most people acknowledge “it’s good for you.” In fact, for many who don’t get pleasure from their exercise, the only reason that they get up early or head to the gym after a long day at the office is because they feel they’re sustaining or improving their health. Most people think about the obvious benefit to their heart from regular cardiovascular activity. Some are concerned about maintaining or improving their appearance, slimming a waistline, or increasing muscle mass. Few, however, think about cancer prevention as a reason to exercise.

Cancer development is often a complex process. Multiple factors act together within our bodies to cause cancer, so it seems wise to have multiple methods to combat them. Avoiding known carcinogens and being vigilant about nutrition are critical, though they may not be sufficient to minimize risk. Regular physical activity can be viewed as an added level of insurance against a cancer diagnosis.

This chapter reviews the best scientific studies available regarding the role of exercise in reducing cancer risk. The focus is on the “big four”: breast cancer, colorectal cancer, lung cancer, and prostate cancer. Some of the results may be surprising.

UTERINE CANCER

Bonnie’s Story

Bonnie was a 72-year-old homemaker who enjoyed baking and spending time with her many nieces and nephews. She had a history of high blood pressure, diabetes, and obesity. She had gone through menopause (“the change of life,” as she described it) at age 55. However, over the past three months, she had noticed that she was getting vaginal bleeding again. She thought that was odd, since she hadn’t had any periods for over 15 years. Bonnie went to her gynecologist, who performed a general pelvic examination that was unremarkable. Since the vaginal bleeding was clearly abnormal, she performed a biopsy of Bonnie’s endometrium (inner lining of the uterus) which revealed adenocarcinoma, uterine cancer. (To be continued….)

Cancer of the uterus is one of the most common gynecologic malignancies. It’s estimated to be diagnosed in 43,000 women in 2010 in the United States, with 8,000 deaths. The median age at diagnosis is 62 years old, and it’s rarely diagnosed before age 30. A woman’s lifetime risk of a uterine cancer diagnosis is 2.5%, or one in 40 women. The overall survival at five years from diagnosis for all stages combined is 83%, according to NCI’s SEER statistics. This relatively high survival rate for uterine cancer is because over two-thirds of patients are diagnosed with localized disease and that group has a five-year survival rate of 96%. Five-year survival for those with regional spread is 67% and for those with metastatic uterine cancer is 17%.

Risks and Causes

Women who have early menarche (start of menstruation; “periods”) and those who’ve never been pregnant and delivered a child (nulliparous) are at increased risk of developing uterine cancer. Women who have taken estrogen pills over years are also at increased risk, although this risk can be minimized by taking progestins for 10 or more days per month. Obesity is also closely linked to an increased risk of uterine cancer. Women who have polycystic ovary syndrome are at increased risk. Lastly, there’s an approximately one in 200 chance of uterine cancer developing in patients who are taking a medication called tamoxifen to reduce their risk of breast cancer. In general, however, the large benefit of tamoxifen in decreasing future breast cancer risk greatly outweighs the small risk of developing uterine cancer for these women.

Signs and Symptoms

The most common symptom of cancer of the uterus is postmenopausal bleeding from the vagina. Once women have gone through menopause (the “change of life”), their menstruation (“periods”) should stop altogether. Although there are occasionally benign reasons for postmenopausal vaginal bleeding, this symptom should always prompt a visit to the gynecologist.

Diagnosis

If a woman presents to her gynecologist with the complaint of postmenopausal bleeding, after the doctor does a thorough physical examination, an endometrial biopsy is usually performed. Contrary to what many people believe, a Pap test (which is done to screen for cancer of the cervix) is not a good test for uterine cancer. The gynecologist must directly biopsy the endometrium (inner lining of the uterus) in order to make a diagnosis of uterine cancer. Among the women who are diagnosed with uterine cancer, about 75% are found to have a type called endometrioid adenocarcinoma. Less commonly, patients may develop sarcomas of the uterus. The most common subtype of uterine sarcoma is called a carcinosarcoma or mixed muellerian tumor, while other types include leiomyosarcoma and stromal sarcoma.

Staging

Laboratory evaluation should include a complete blood count, serum chemistries including kidney and liver function, as well as a CA125 level. This blood test serves as a reasonable measure of the extent of microscopic uterine cancer that exists throughout the body and may be elevated in 60% of patients. If a woman’s CA125 level is well above normal before surgery, there’s a very good chance that cancer has spread outside the uterus. Imaging generally includes CT of the chest, abdomen and pelvis for patients with locally advanced disease, or if the primary tumor is a type of sarcoma. Patients also undergo cystoscopy and proctoscopy by a gynecologic oncologist, a surgical specialist in the treatment of female cancers. These tests involve direct visualization of the lining of the bladder and rectum, respectively, to ensure that cancer hasn’t grossly invaded these nearby organs, which would indicate more advanced stage. While uterine cancer staging has classically been the FIGO system, the AJCC TNM system is now also widely used. Although most women have stage I disease that’s limited to the endometrium or myometrium (deep muscle wall of the uterus), some patients present with more advanced diseased that’s spread to other parts of the pelvis including lymph nodes. When metastases occur, they do so most commonly to the lungs or liver. The five-year survival by stage is approximately as follows: stage I-90%, stage II-70%, stage III-40%, and stage IV-10%.

After the stage, the next most important factor for predicting survival of uterine cancer is the grade of the tumor. Grade describes how aggressive the cells appear under the microscope, or how different the cells appear from normal uterine cells. Other factors that may predict prognosis for women with uterine cancer include patient age and overall condition, the presence or absence of cancer cells in lymphatic and blood vessel spaces, and the level of the patient’s hemoglobin (the protein in blood that carries oxygen).

Treatment

The mainstay of treatment for cancer of the endometrium or uterus is surgical removal of the uterus, fallopian tubes, and ovaries by a gynecologic oncologist. This procedure is called a total abdominal hysterectomy, bilateral salpingo-oophorectomy, (TAH/BSO). During the surgery, sterile water is rinsed through the pelvis and abdomen, and the “washings” are sent with the surgical specimen so that the pathologist may review both to ensure that no cancer cells have escaped into these areas. Pelvic lymphadenectomy (removal or dissection of lymph nodes in the pelvis) has been part of the standard operation in the United States. At least two major RCTs have shown no benefit to pelvic lymphadenectomy in terms of survival or cancer recurrence. However, results of the lymph node dissection are often used in the United States to guide postoperative treatment recommendations. Comparisons of laparotomy (conventional open surgery) versus laparoscopy (making small incisions and placing a fiberoptic camera within the abdomen to guide surgery) have shown a small benefit to patients’ quality of life with laparoscopy. Gynecologic oncologists at major cancer centers are now often performing these surgeries with robot assistance. In addition to the common surgical risks of bleeding, infection, and postoperative pain, side effects of hysterectomy for uterine cancer include nausea, small risk of bowel obstruction, and sexual dysfunction.

Very early stage patients don’t require any postoperative treatment. Those with stage I disease that either invades deeply into the uterine muscle wall or has more aggressive, higher grade cancer cells may benefit from local postoperative internal radiation therapy (RT). These treatments are delivered to the top of the vagina, which is the most likely place for cancer to return following surgery. This type of internal RT is most commonly delivered on an outpatient basis by a radiation oncologist, a physician who specializes in the treatment of cancers with radiation. High dose rate (HDR) brachytherapy treatments are delivered in a few (usually three) outpatient weekly sessions. “Brachy” is Greek for “short,” which describes the distance over which the internal RT travels. The treatment is called vaginal brachytherapy (VBT). The radiation oncologist places a cylinder into the patient’s vagina which contains a central channel through which the radiation source travels from the HDR brachytherapy machine. The prescribed amount of RT is then delivered to the top portion of the vagina painlessly over a short time (five to 15 minutes) during each session. The RT dose to normal tissues even a couple of inches away from the top of the vagina with VBT is very low. Most women tolerate this treatment without acute side effects other than the mild discomfort of having the cylinder inserted into the vagina. An uncommon, long-term side effect called vaginal stenosis (scarring of the tissues at the top of the vagina) may cause pain. The risk of vaginal stenosis can be minimized by use of a vaginal dilator that keeps the tissues flexible and healthy.

Patients who have evidence of cancer cells outside the uterus but within the pelvis may benefit from postoperative pelvic external beam RT. As mentioned above, a pelvic lymphadenectomy is routinely performed during surgery in the United States in order to help guide recommendations for postoperative treatment. Most women who have aggressive features of the primary cancer but don’t undergo a lymph node dissection should have postoperative RT to the pelvis in order to improve local control. In these patients, RT decreases the risk of cancer returning in the pelvis. Many women in Europe are treated in this manner, since pelvic lymphadenectomy is performed much less frequently there. However, even after a formal lymph node dissection is performed, some patients may benefit from postoperative pelvic RT. These include women with multiple positive lymph nodes and other high-risk features including tumor invasion of blood vessels or lymphatics extensively. In an RCT that enrolled over 500 women with uterine cancer, women whose tumors invaded nearby blood vessels had three times the risk of dying of their cancer. This same trial showed that for patients with stage I cancer, only those whose cancers invaded into deep uterine muscle or were high grade benefited from RT to the pelvis.

Postoperative pelvic RT was tested in another major RCT called the PORTEC (postoperative radiation therapy in endometrial cancer) study. In this European trial, women did not have pelvic lymph nodes removed. Postoperative RT to the pelvis decreased the chance of cancer returning in the pelvis, but didn’t improve patients’ overall survival. The more recent PORTEC-2 trial from the Netherlands randomized patients with “high-intermediate risk” stage I and IIa uterine cancer to three VBT treatments versus four-and-a-half weeks of daily external beam RT to the pelvis. VBT resulted in fewer bowel side effects and similar survival to pelvic RT. Therefore, the investigators recommended that VBT should be the standard postoperative treatment for this group of women. Side effects of pelvic RT include acute irritation of the bladder and bowels that usually gets better by two to three weeks after RT is completed. There’s a small risk of long-term problems with urination or bowel movements chronically after postoperative pelvic RT. The chance of a severe complication (such as one that would require surgery to repair) with standard pelvic RT is about 3%, according to the PORTEC trial results.

Patients who have advanced disease and are in good overall condition should receive postoperative chemotherapy for improved survival. Some of the medications that are used in the systemic treatment of uterine cancer include carboplatin, cisplatin, cyclophosphamide, doxorubicin, and paclitaxel. A very effective combination that’s used in the United States is cisplatin and doxorubicin. A recent RCT performed by the Gynecologic Oncology Group (GOG) revealed no clear survival benefit to adding paclitaxel to the other two drugs. Another interesting GOG trial revealed that cisplatin and doxorubicin chemotherapy improved survival over RT to the whole abdomen for women with advanced disease. The combination of carboplatin and paclitaxel is also commonly used. Acute side effects of chemotherapy for uterine cancer include fatigue, nausea, vomiting, poor appetite, decreased blood counts, joint aches, and rare chance of long-term injury to heart, nerves, kidneys, or hearing.

Women who are diagnosed with metastatic uterine cancer that’s spread to other organs, such as the liver or lungs, don’t live any longer by having their uterus removed. Women with metastatic disease who are in good condition or are having symptoms are usually treated with similar chemotherapy agents to those with locally advanced disease. Side effects are also similar.

Bonnie’s Uterine Cancer Treatment & Outcome

Bonnie’s gynecologist referred her to a gynecologic oncologist, who performed a total abdominal hysterectomy, bilateral oophorectomy (TAH/BSO), with pelvic washings and lymph node dissection. Her tumor invaded into the uterine muscle layer to a depth of 1.5 cm of a total thickness of 2.0 cm and was grade 2. She had no cancer in multiple lymph nodes. Her stage was T1cN0M0. She recovered over four weeks and was referred to a radiation oncologist. This specialist recommended postoperative VBT to the top of the vagina to decrease the risk of the cancer returning there. She underwent three of these weekly outpatient treatments in the radiation oncology clinic with mild discomfort but no major side effects. Bonnie is alive without evidence of disease eight years later. She continues to win the county pie baking contest every year!