In today’s fast-paced world, waiting — whether it’s at the doctor’s office, in line at the grocery store or for an Internet connection — is rarely considered a good thing.

But when it comes to certain medical conditions, delaying treatment while regularly monitoring the progress of disease — a strategy doctors refer to as “watchful waiting,” active surveillance or expectant management — may benefit some patients more than a rush to pharmaceutical or surgical options.

Patients want to know what they’re waiting for, says urologic oncologist E. David Crawford, MD, chairman of the Prostate Conditions Education Council and associate director of the University of Colorado Comprehensive Cancer Center.

The purpose is to watch in order to see whether a condition progresses. That way, patients and physicians know what kind of threat a disorder poses and they can make a better decision about how urgently treatment is needed. Some people might never need treatment, for instance with a slow-growing cancer. Other people can delay treatment for months or years.

Precancerous conditions may also be monitored with active surveillance. One example is ductal carcinoma in situ (DCIS), or abnormal changes in the ducts of the breast. DCIS may eventually progress into an invasive form of cancer, but most cases do not, so some physicians promote regular monitoring to avoid or delay the side effects of breast surgery, chemotherapy or radiation.

Often, active surveillance is associated with cancer treatment, particularly cancers that may progress slowly. There’s evidence that active surveillance offers particular benefit for prostate cancer, follicular lymphoma, myeloma and chronic lymphocytic leukemia. Ovarian, endometrial and uterine cancer might also warrant active surveillance at some point during treatment.

When Syd Ball, a nuclear engineer from Tennessee, was diagnosed with prostate cancer, he chose active surveillance over immediate surgery or radiation therapy.

“When I was diagnosed, it did shake me up,” Ball said. “Once I talked to the doctor, and got the statistics about my chances, then I felt there was no question about what to do. Being an engineer, if you give me the risk statistics on it, I’ll tend to believe that the best course of action is based on what my chances are.”

Watchful waiting allowed Ball and his physician to get a better idea of his risk — whether his cancer was growing and how quickly. If the cancer grew quickly, then he knew he should start treatment. If not, he could wait. Ball was not looking forward to possible treatment side effects that could interfere with his quality of life and wanted to delay or avoid them if possible.

The concept of active surveillance isn’t limited to cancer treatment. It occurs across a variety of medical conditions. Pediatricians or family doctors may recommend watchful waiting for children with ear infections, since many resolve without treatment from antibiotics.

Physicians who treat chronic lower back pain might employ watchful waiting, monitoring patients regularly instead of immediately performing surgery to see if symptoms resolve on their own or whether stress management, strengthening exercises and other strategies effectively manage pain.

The physicians of couples trying to conceive a child sometimes suggest watchful waiting for a period of time before starting infertility tests and treatments, because most healthy partners conceive within a year without added intervention.

Women with endometriosis whose pain isn’t severe, who do not want to have children or who are approaching menopause may choose active surveillance, rather than deal with the side effects of surgery or hormonal treatments. And women with ovarian cysts who have mild or no symptoms might be advised to delay active treatments until symptoms become severe, because surgery carries the risk of infection and bowel and bladder damage.

What Happens While You Wait?

Though it’s a common misconception among patients, watchful waiting isn’t just ignoring the disease or disorder, hoping it will go away. “Active surveillance is a term that defines the fact that it’s not just wishful waiting or delayed treatment,” Crawford says. Physicians actively monitor the situation, and if needed, will jump in and begin active treatment, he says.

If you and your physician agree that active surveillance is a good idea, you’ll need regular checkups, and, depending on your condition, medical testing, such as blood tests, biopsies or imaging scans like MRIs or CAT scans, will be part of your regular monitoring. For conditions like chronic back pain, your doctor may recommend you make changes to your dietary habits, exercise regimen or lifestyle.

“We don’t want to let things fall through the cracks. With active surveillance, frequently we would be following patients as often as you would when they are on treatment, checking tumor markers and monitoring for new problems or symptoms they might have,” says Deborah Armstrong, MD, an associate professor of both oncology and of gynecology and obstetrics at the Johns Hopkins University School of Medicine. “It is different from someone who is at the end of their treatment options. It’s not ‘Should I try this?’ That’s a different concept. The concept of watchful waiting is that you do plan that you will be starting treatment but you’re going to delay it.”

The length of time active surveillance is recommended varies from person to person and is based on a variety of factors, including your age and general health, how severe your symptoms are, how quickly the disease progresses and the risks of delay. Physicians may monitor some patients, such as Syd Ball, for more than a decade without changing course. In other cases, active surveillance may take place for only for a few months ─ or in the case of ear infections, a few days ─ before having to move on to active treatment.

Nikkie Hartmann, a public relations professional from Chicago, came to the process of active surveillance after more than a decade of battling papillary thyroid cancer. Hartmann, given a cancer diagnosis during her freshman year of college, underwent total thyroid removal surgery, as well as radioactive iodine treatments. Though her blood tests still show elevated levels of cancer markers, the side effects of the radioactive iodine treatments and lymph node biopsies have proved uncomfortable and time consuming ─ and the active surveillance offers a break from the treatments while keeping an eye on her disease.

“The doctor didn’t use the phrase watchful waiting or active surveillance, but he said ‘watch and wait,’” Hartmann said. Though she’s still monitored with blood tests and will require additional diagnostic testing and possible treatments if she chooses to have children, within the last year Hartmann and her doctors have adopted an active surveillance stance that delays radioactive iodine treatments and lymph node biopsies for now.

Knowing the side effects that biopsies and radioactive iodine treatments can cause, Hartmann says that she’s at peace with the decision. “I was relieved when they told me that they recommended watching and waiting,” Hartmann said.

Waiting Isn’t for Everyone

Active surveillance is not without risks, however. For some types of cancer, for example, there’s a risk that the cancer may be harder to control if treatment is delayed. Doctors do not recommend active surveillance for fast-growing, aggressive or late-stage treatable cancers.

For other conditions, such as chronic back pain or endometriosis, there’s the risk that painful symptoms may worsen during active surveillance, eroding quality of life and making it difficult to work.

Though active surveillance offers a delay in the physical symptoms caused by treatment, the emotional issues associated with this choice prove difficult for some patients to handle.

“A lot of difficulty comes from the historical context of how we’ve treated cancer,” said Jamie Studts, Ph.D., a psychologist who treats oncology patients and an associate professor at the University of Kentucky College of Medicine. “The idea is very foreign to people that you have cancer in your body and you’re not doing anything to get it out.”

It takes a significant discussion and a decision-making process shared between doctor and patient to understand the pros and cons and how that can be the best way to manage their care at a particular time, Studts says.

“The other problem is the perception of potential rationing of care,” Studts adds. Particularly if people don’t have resources, they could feel like they’re being mistreated or undertreated or not treated fairly if active surveillance is suggested.

But Dr. Armstrong offers reassurance that active surveillance doesn’t mean less face time with your physician: “I spend as much time with these patients as with patients I’m treating. At every point we say, ‘If we see this, we are going to do this. Let’s see what the disease looks like, then we’ll decide if we need to do treatment.’”

For some people, the anxiety of watchful waiting cannot be overcome, Armstrong said. Regardless of the statistics and the doctor’s recommendation, patients who could benefit from active surveillance sometimes insist on and receive treatment instead.

In addition, the influence of a family member or partner who doesn’t fully support active surveillance may erode a person’s initial decision to use it, Dr. Studts says.

Making the Decision

“Watchful waiting may allow people to have a good quality of life and have the tumor completely arrested. Take diabetes. You don’t cure diabetes, you manage it. With cancer, maybe we don’t have to get it all, maybe we can arrest it or stop it so it doesn’t spread or doesn’t affect major organ systems,” Studts said.

So how do you decide whether active surveillance is for you?

The starting point for making the decision is a trusting relationship with your physician, Armstrong says. “This is a situation where patients have to have trust in the physician, trust that the physician is doing the right thing. It’s easier to treat someone than it is to do watchful waiting. The main issue is that people need to be comfortable with the concept and their doctor is doing the right thing,” Armstrong says.

“Trust your gut if it doesn’t feel right and get a second opinion. You have to be your own advocate, and if you don’t feel comfortable, get more information,” Hartmann says.

This is reprinted with permission from the Center for Advancing Health’s Health Behavior News Service and/or Prepared Patient Forum What It Takes blog.

Article from http://www.cfah.org/hbns/index.cfm

A study to be published in August 2011 suggests that men are undergoing prostate cancer surgery with unrealistic expectations regarding their recovery of urinary control and sexual function, in spite of getting “the facts” in counselling sessions.

“Men have unrealistic expectations of urinary and sexual function after prostatectomy despite preoperative counseling,” says the study available online from the Journal of Urology.

Researchers recruited men who were scheduled to have a radical prostatectomy between June 2007 and November 2008. These men were given extensive counselling about the usual outcomes, including information about the statistical risk of incontinence and erectile dysfunction.

Then these men filled out a questionnaire before they had surgery (but after having received counselling). The questions asked them about what they expected in terms of their urinary, bowel, and sexual function at one year after the surgery. Of the men, 36 percent expected that, one year after surgery, they would have the same urinary control as before surgery, and 40 percent thought they would have the same sexual function. Surprisingly, even after counselling, some men expected to have better urinary and sexual function a year after surgery, 12 percent and 17 percent, respectively. This belief, says lead researcher Daniela Wittmann of the University of Michigan, is “out of step with reality.”

When the men completed a survey a year after surgery, 47 percent had attained lower than expected urinary control and 44 percent lower than expected sexual function.

The researchers speculate that the same “psychological mechanisms” that can help men heal—emotions such as optimism, for example—may be the cause of these unrealistic expectations.

“We can only [inform men] in terms of overall statistics; we can’t predict for the individual man, which means that, if in doubt, people tend toward being hopeful and optimistic,” Wittmann says.

Commenting on this study, Tracey Krupski of the University of Virginia suggests that support networks can really help new cancer patients facing these treatment side effects. Often, men need this support to approach their doctors with questions about these worrying but non-life-threatening side effects. And, if no treatment is effective or possible, a support network can help men adjust to the “new normal.”

According to Wittmann, involving the partners of men with prostate cancer is fundamental in counselling and in helping men cope with the realities of life after surgery.

“Sex is a partnered activity for most people. The partner can be very effective as part of an intimate team recovering from the side effects of this surgery,” she says.

See the new PCCN pages on coping with urinary incontinence and erectile dysfunction after prostate cancer treatment.

References:

Dianiela Wittmann and colleagues, 2011, Patient preoperative expectations of urinary, bowel, hormonal, and sexual functioning do not match actual outcomes 1 year after radical prostatectomy, Journal of Urology, vol. 186, no. 2, 494–499.

Article from http://www.prostatecancer.ca/PCCN.aspx

The most explicit call to date for expanding the use of active surveillance in the treatment of prostate cancer was made last week by the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of leading cancer centers. Updated guidelines from an NCCN panel urge clinicians to offer active surveillance to their patients whose prostate cancers are at low risk of progressing to life-threatening disease.

Active surveillance—in the past also called “watchful waiting” and “expectant management”—refers to a strategy of forgoing immediate treatment after a diagnosis of prostate cancer in favor of regularly scheduled testing and clinical exams to closely monitor the disease. Active surveillance can include prostate-specific antigen (PSA) testing, digital rectal exams (DRE), and prostate biopsies. If, at some point, there are indications that the disease is progressing—such as significant growth in the tumor or a rapid increase in PSA level or higher tumor grade on biopsy—definitive treatments such as surgery or radiation therapy can be pursued.

Of the more than 192,000 estimated prostate cancer cases diagnosed in 2009, about half may fall in the low-risk category, explained Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis.

Under the updated guidelines (available online with free registration), active surveillance should be recommended to men with low-risk prostate cancer who have a life expectancy of less than 10 years. Men with low-risk cancers have a relatively low PSA level and their tumors are small, confined to one side of the prostate, and have a low tumor grade, or Gleason score (see sidebar). The guidelines also established a new category of very-low risk, or clinically insignificant prostate cancer. In men with a life expectancy of up to 20 years who fall into this new category, the guidelines recommend advising only active surveillance as the preferred management approach.

“The entire [prostate cancer] treatment committee is concerned about the overdiagnosis and overtreatment of prostate cancer,” explained the panel’s chair Dr. James L. Mohler from the Roswell Park Cancer Institute. The impetus for the update, Dr. Mohler continued, was the publication last year of results from two large clinical trials of prostate cancer screening that showed there was significant overdiagnosis and overtreatment of cancers that likely would have never been a cause for concern.

“Most men find out that they have prostate cancer and what do they want? They want it gone,” Dr. Mohler said. “There are too many men suffering the side effects of treatment, and society is bearing the costs of those treatments. And too much of it is unnecessary.”

To that point, a study published last September estimated that, since 1986, as many as 1 million men have received definitive treatment for a prostate cancer (diagnosed as a result of PSA screening) that would have never threatened their lives. Despite the concerns about overtreatment and the call to expand active surveillance, Dr. Mohler stressed that it’s still an individual decision that patients must make in consultation with their physicians.

Although there are clear benefits to active surveillance in the appropriate patients, the guidelines panel noted that choosing this treatment approach is not a simple process or decision. In addition to the need for frequent exams and tests, from a disease perspective, waiting to see if the cancer progresses could eventually mean having to treat a more aggressive tumor, with a lower likelihood of cure and a greater risk of serious side effects.

The risk of such progression, Drs. Mann and Mohler agreed, is low. According to Dr. Mohler, the risk of a significant tumor grade increase is around 5 percent, and the risk of an increase in PSA is between 16 and 25 percent.

No data have been published from randomized clinical trials directly comparing active surveillance to immediate, definitive treatment. But based on the available evidence, Dr. Mann said, “In low-risk patients, active surveillance with delayed curative intervention is an acceptable strategy.” That contention is supported by two recently published studies (here and here) which both reported equivalent long-term cancer mortality outcomes in men who opted for active surveillance compared with those who received immediate, definitive treatment. (See the cancer research highlight in this issue on a comparative effectiveness study released last week.)

Dr. Paul Godley, a medical oncologist at the University of North Carolina Lineberger Comprehensive Cancer Center, said the recommendations are overdue. However, he noted, there are still questions about active surveillance that need to be worked out, including the appropriate trigger for transitioning to definitive treatment. “I think that will still be fairly subjective based on what the patient and his physician are comfortable with,” he said.

There’s also the matter of how clinicians will react to the updated recommendations, given that immediate, definitive treatment appears to be a fairly ingrained practice. An online poll conducted January 2009 via the New England Journal of Medicine, for instance, presented a case example of a 63-year-old man with low-risk prostate cancer. Among the respondents from the United States (not all of whom were clinicians), approximately 70 percent chose either radiation therapy or surgery over active surveillance as the preferred management option.

It is unclear, Dr. Godley said, whether the recommendation “will make the trend lines change a whole lot.” But, he continued, “it may make some physicians more comfortable with doing active surveillance themselves or referring patients to a group that is using it in their low-risk patients.”

—Carmen Phillips
Article from http://www.cancer.gov/

Initial, independent review of study data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health shows that selenium and vitamin E supplements, taken either alone or together, did not prevent prostate cancer. The data also showed two concerning trends: a small but not statistically significant increase in the number of prostate cancer cases among the over 35,000 men age 50 and older in the trial taking only vitamin E and a small, but not statistically significant increase in the number of cases of adult onset diabetes in men taking only selenium (10 percent for those taking selenium vs. 9.3 percent taking placebo). Neither of these findings proves an increased risk from the supplements and both may be due to chance.

The Southwest Oncology Group (SWOG), an international network of research institutions, coordinates SELECT at more than 400 clinical sites in the United States, Puerto Rico, and Canada.

Data and additional analyses of the SELECT trial were published online December 9, 2008, in JAMA. Among the specific results highlighted, the five-year rate of prostate cancer diagnosis in the four arms of the study was 4.43 percent in the placebo arm of the trial, 4.56 percent in the selenium arm, 4.93 percent in the vitamin E arm (the highest rate, but one that does not show a statistically significant difference from the placebo arm), and 4.56 percent in the selenium plus vitamin E arm.

Adherence to the study protocol dropped off from year one to year five (83 percent adherent vs. 65 percent at year five), which was expected and did not affect the trial outcome.

SELECT participants received letters in October 2008 explaining the study review and telling them to stop taking their study supplements. Participants will continue to have their health monitored by study staff, which may include regular digital rectal exams and PSA (prostate-specific antigen) tests to detect prostate cancer. Investigators intend to follow the participants for about three years to determine the long-term effects of having taken either supplement or placebo and to complete a biorepository of blood samples that will be used in extensive molecular analyses to give researchers a better understanding of prostate cancer, other cancers, and other diseases of male aging. This additional data collection is a vital part of the study.

Neither the men nor their physicians know which supplements or placebos the men have been taking, a procedure known as blinding or masking. As followup of the SELECT participants continues, the participants will continue to be blinded. A blinded followup may avoid unintentional bias and potentially false conclusions. However, at the request of a participant, they will be informed which supplement, if any, they received.

“SELECT was always designed as a study that would answer more than a single question about prostate cancer,” said Eric Klein, M.D., a study co-chair for SELECT, and a physician at the Cleveland Clinic. “As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so.”

SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer was not the primary outcome: a 1998 study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer surprisingly showed 32 percent fewer prostate cancers in men who took the supplement, and a 1996 study of 1,312 men and women with skin cancer who took selenium for prevention of the disease showed that men who took the supplement had 52 percent fewer prostate cancers than men who did not take the supplement.

Based on these and other earlier findings, in 2001, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.

It should be noted that in 2003, while SELECT was recruiting men, a different SWOG-sponsored study reported that the drug finasteride reduced the incidence of prostate cancer by 25 percent. When this was discovered, men on SELECT were informed and allowed to take finasteride (4.8 percent of men, not on the other SWOG study, took the drug at some time during the SELECT trial). Finasteride has not yet been approved by the U.S. Food and Drug Administration for prostate cancer prevention.

Except for skin cancer, prostate cancer is the most common type of cancer in men in the United States. In 2008, there will be an estimated 186,320 new cases of prostate cancer and 28,660 deaths from this disease in the United States. “Finding methods to prevent and treat prostate cancer remains a priority for the NCI, and with the aid of new molecular diagnostic tools and applications, we hope to continue to make headway in reducing deaths and new cases of this disease,” said NCI director John E. Niederhuber, M.D. “The science of cancer prevention is also leading toward individualized, molecular prevention, in which we will calculate risk and design preventive steps based on an individual’s genome.”

SELECT has been funded by NCI for $114 million, with additional monies from the National Center for Complementary and Alternative Medicine, and with substudies funded and conducted by the National Heart, Lung and Blood Institute, the National Institute of Aging and the National Eye Institute at NIH. The substudies were evaluating the effects of selenium and vitamin E on chronic obstructive pulmonary disease, the development of Alzheimer’s disease, and the development of macular degeneration and cataracts, and will continue without participants taking study supplements. An NCI-funded substudy is looking at the effects of the supplements on men who developed colon polyps.

“The SELECT trial owes a tremendous debt to our volunteers, the thousands of men who offered their time and enthusiastic participation, all in the interest of a future when prostate cancer can be prevented,” said Laurence H. Baker, D.O., chairman of the Southwest Oncology Group. SELECT investigators are analyzing the data and will submit the analysis for publication in a peer-reviewed medical journal.

Reference: Lippman SM, Klein EA, Goodman PJ, et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers. JAMA. Published online December 9, 2008.
Article from http://www.cancer.gov/

Laboratory experiments show that an extract of the skin of muscadine grapes can inhibit growth of prostate cancer cells in the laboratory. Investigators from the National Cancer Institute (NCI), part of the National Institutes of Health, and their research partners also show that muscadine grape skin extract (MSKE) does not contain significant amounts of resveratrol, another grape skin component that has been widely studied and shown to be of potential benefit in preventing prostate cancer growth. The results appear in the September 1, 2007, issue of Cancer Research.

Using a series of human prostate cancer cells, representing different stages of prostate cancer progression, the researchers showed that MSKE significantly inhibits the growth of cancerous, but not normal, prostate cells, primarily by inducing a process called apoptosis, or programmed cell death. Programmed cell death is one of the mechanisms the body uses to rid itself of cells with unrepaired genetic damage before those cells can duplicate themselves. In contrast, resveratrol seems to act by blocking the cell cycle, a sequence of steps that a cell passes through when it grows and divides into two identical cells. Both mechanisms are used by the body to prevent the development of cancer.

According to Jeffrey E. Green, M.D., chief of the Transgenic Oncogenesis and Genomics Section in NCI’s Center for Cancer Research (CCR), “These results show that MSKE may have potent antitumor activities in the lab that differ from the effects of resveratrol. Further studies of MSKE will be necessary to determine if this extract has potential as a chemopreventive or therapeutic agent.”

The fact that all of the cells studied, which cover the different stages of prostate cancer tumor progression, responded to MSKE suggests that the active compounds in this extract may inhibit tumor development at very early stages.

The muscadine grape (Vitis rotundifolia) is distinct from the more common red grapes used to produce red wines, a major source of resveratrol. The chemical constituents of muscadine grapes differ from most other grape varieties, as they are richer in chemicals called anthocyanins. Anthocyanins, which produce the red and purple colors of the grapes, have strong antioxidant activity and have shown several antitumor effects, including inhibition of DNA synthesis in breast cancer cells, of blood vessel growth in some tumors, and of enzymes involved in tumor spread. Muscadine grapes can be found growing wild from Delaware to the Gulf of Mexico and westward from Missouri to Texas.

While previous studies suggested that anthocyanins might suppress the cancer process, no rigorous study of the mechanisms underlying these effects has yet been done. Resveratrol, by contrast, has been widely examined. Although earlier studies showed that it can induce programmed cell death in prostate cancer cells, resveratrol did not significantly induce cell death in the prostate cell model system used for this muscadine study. The results of this study suggest that resveratrol may activate different antitumor mechanisms than MSKE.

Even though MSKE had significant inhibitory effects on the prostate cancer cells studied, it did not alter the growth rate of the normal human prostate cells in the lab, which served as controls. Ongoing studies of MSKE in animals will help to determine the underlying mechanisms of MSKE’s inhibitory effects in prostate cancer cells. The researchers hope that the lab effects of MSKE will be reproducible in testing on cancerous and normal prostate cells in animals. Should MSKE move on to trials in humans, Green says that since “muscadine grape products, including grape juice and grape wine, have been used in human studies without reported side effects, they may be relatively safe for use in clinical trials.”

Article from http://www.nih.gov/news/