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Screening for Prostate Cancer in Long-Term Care

Citation

Pages 22 - 28

Authors

Holly M. Holmes, MD, and James S. Goodwin, MD

Prostate cancer is a common disease and is the second leading cause of cancer-related death in men. However, many older men with prostate cancer will die from comorbid illness rather than cancer. Survival from prostate cancer with available treatment options, including surgery, radiation, androgen suppression, and watchful waiting, is mediated by age, tumor grade, and comorbid illness. Due to the long natural history of prostate cancer and the presence of competing comorbidities, the majority of elderly men with newly diagnosed prostate cancer will not benefit from curative therapy. Even more relevant to the long-term care population is the further lack of benefit from diagnosing early-stage prostate cancer in men with advanced age, multiple comorbidities, and a high prevalence of dementia. Thus, in the long-term care population, a rational approach to the detection of prostate cancer is to evaluate suspected symptomatic or metastatic disease exclusively. (Annals of Long-Term Care: Clinical Care and Aging 2009;17[11]:22-28)
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Introduction

Although prostate cancer is a common cause of cancer-related mortality in men, the majority of men with prostate cancer will not die from the disease. Most patients present with localized disease, and men who are diagnosed with low-grade prostate cancer are more likely to die from comorbidities rather than from the cancer.1,2

With increasing age and increasing number and severity of comorbid illnesses, the impact of the stage of prostate cancer at diagnosis on survival diminishes. Thus, the benefit of diagnosing earlier stage disease through regular screening is not achieved, while the risk of physical and emotional discomfort that may result from screening persists.

The purpose of this review is to discuss recommendations for the evaluation of prostate cancer in men residing in long-term care (LTC). As such patients have multiple comorbidities and a limited life expectancy, a discussion of the detection and subsequent treatment of prostate cancer in this vulnerable population is warranted. Due to the indolent nature of the disease, the high incidence in elderly men, and the risk-benefit ratio for treating prostate cancer in men with a life expectancy of 10 years or less, screening for prostate cancer in LTC settings should not be routine. Symptoms of prostate cancer should be evaluated and treated, but a diagnosis of prostate cancer should be pursued only when symptomatic disease is suspected.

Background

Prostate cancer is the most common cancer in men. In the United States in 2007, over 200,000 new cases of prostate cancer were diagnosed, and 27,000 deaths were attributed to prostate cancer. Despite the fact that prostate cancer is the second leading cause of cancer death in men, it causes only about 3% of all deaths in men.3

The incidence of prostate cancer in the United States rose significantly between 1987 and 1992. This increase is attributable to the widespread screening for prostate cancer using the prostate-specific antigen (PSA) test. Figure 1 shows the trend of increasing incidence of prostate cancer in the Surveillance, Epidemiology, and End Results Program.

The most significant risk factor for the development of prostate cancer is age. Most new cases of prostate cancer are diagnosed in men over the age of 65 years. Prostate cancer becomes increasingly common with advancing age; at autopsy, an estimated 50% of men age 80 years and older have evidence of prostate cancer.1 A review of more than 19,000 routine autopsies in men age 40 years and older showed that 8.2% had prostate cancer, and roughly half of these were not clinically apparent.4 Other risk factors for the development of prostate cancer include genetic and environmental factors, race, and family history. Men who have a first-degree relative with prostate cancer are twice as likely to be diagnosed with the disease. Race is a significant factor in incidence, stage at diagnosis, and mortality from prostate cancer. African Americans have higher rates of prostate cancer incidence and mortality than whites, Hispanics, and other populations.1

Cancer is less prevalent in institutionalized elderly persons as compared to community-dwelling individuals. Approximately 20% of men age 85 years and older have cancer, but only 5.7% of institutionalized older men have cancer.5 Prostate cancer accounts for about 10% of new cancers diagnosed in the nursing home (NH).6 Lower cancer rates in LTC populations could be due to decreased screening and reporting rates in such patients, who are more likely to be frail and cognitively impaired. Another potential explanation for the lower cancer rate is host factors, attributable to conditions such as frailty, that may create a less conducive environment to the development of cancer.5

Prostate cancer is generally asymptomatic on presentation, and approximately 90% of men are diagnosed with localized disease.3 The diagnosis of prostate cancer is made after an abnormal PSA test and/or abnormal digital rectal exam (DRE) leads to a transrectal ultrasound and biopsy. Symptoms of urinary frequency, nocturia, and hesitancy are more likely due to benign prostatic hypertrophy and not due to prostate cancer.7 A small number of men—6.4% of men with prostate cancer in the National Cancer Data Base in 1998—are diagnosed with metastatic disease, which can present with symptoms of bony pain or spinal cord compression.8

Impact of the PSA Test

More than half of men in the United States have reported regular PSA screening.9 Although mortality from prostate cancer has decreased, no study has established an effect on mortality from PSA screening.9 Due to lead time bias and increasing efficacy of available treatments, the improvement in mortality may not be related to the use of PSA testing.9 PSA testing increases the lead time for prostate cancer detection by 5-15 years, but long-term studies of prostate cancer treatment outcomes enrolled patients who were not diagnosed with PSA testing.10 The estimated likelihood of detecting clinically insignificant disease in a 75-year-old man is 56%.10

A PSA level below 4.0 ng/mL most likely indicates benign disease. Values above 10.0 ng/mL are indicative of cancer. However, values between 4.0 ng/mL and 10.0 ng/mL are not diagnostic and prompt further testing with a transrectal ultrasound and biopsy. In the Prostate Cancer Prevention Trial, which compared the effect of finasteride to placebo on prostate cancer prevalence in a 7-year period, men in the placebo arm underwent annual PSA and DRE testing, and they were asked to undergo a prostate biopsy after an abnormal DRE or a PSA above 4.0 ng/mL and at the end of the study, regardless of PSA and DRE results. Sixty-five percent of men in the placebo arm who had DRE and PSA results available underwent at least one prostate biopsy. Of the biopsies performed in the trial, 21.9% showed cancer; 20.6% of those were Gleason grade 7 or greater, and 4.7% were Gleason grade 8 or greater.9 However, 15% of men with a PSA result of 4.0 ng/mL or less had prostate cancer on biopsy.11 Overall, the results of the trial supported the challenge that no clear cutpoint with high specificity and sensitivity for the PSA exists; rather, there is a spectrum of prostate cancer risk among all values for the PSA.

 

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Treatment Options

Treatment for prostate cancer includes watchful waiting (which may include observation or active surveillance with regular PSA testing and prostate biopsy), surgery (radical prostatectomy), radiation therapy (including external-beam radiation therapy and brachytherapy), and androgen deprivation therapy. The treatment decision must include a consideration of the risk of progression, morbidity, or mortality without treatment, and costs, side effects, and the benefits of each treatment.12

Few high-quality randomized controlled trials have been conducted to establish differences between the available treatments when used in localized disease. Obvious benefit has not been established for any of the treatments, and all of the treatments have associated harms. Most of the studies of outcomes for each treatment option have enrolled patients before the widespread use of PSA testing to detect prostate cancer. In addition, many trials did not evaluate outcomes on the basis of patient age at diagnosis or histologic grade or tumor stage, factors known to affect survival in prostate cancer.12

Radical Prostatectomy

Most men diagnosed with prostate cancer, especially younger men with localized disease, undergo radical prostatectomy. In the one major randomized controlled trial comparing surgery with watchful waiting, radical prostatectomy reduced metastasis by 10.2% and local tumor progression by 25% as compared to watchful waiting in men younger than age 75 with localized disease, and resulted in an absolute reduction in overall mortality of 5.3% after 10 years.13 However, the reduction in disease-specific mortality was seen almost entirely in patients younger than age 65.13 Figure 2 shows the effect of age on survival comparing surgery to watchful waiting. Complications of prostatectomy include urinary incontinence, sexual dysfunction, and bowel dysfunction, including diarrhea and lower gastrointestinal (GI) bleeding. Using more recent nerve-sparing techniques, up to 85% of men recover erectile function.14

Radiation Therapy

Several trials have compared different radiotherapy modalities, and no regimen is better than any other in reducing prostate cancer or overall mortality.12 In men with low-grade disease, higher radiation doses improved rates of PSA relapse, with 10-year disease-free survival rates of 85% versus 58% with lower radiation doses.15 Combining radiation with 6 months of androgen deprivation therapy resulted in 8-year overall survival rates of 61% with radiation alone versus 74% for radiation with androgen deprivation in men with localized prostate cancer and one unfavorable prognostic factor (PSA > 10 ng/mL, Gleason 7-10, extracapsular disease, or seminal vesicle invasion).16 However, men with an Adult Comorbidity Evaluation 27 score of 2 (moderate decompensation of 1 organ system) or 3 (moderate decompensation in 2 organ systems or severe decompensation of an organ system) had no difference in all-cause mortality between radiotherapy alone versus radiotherapy plus androgen deprivation therapy.16 Figure 3 shows the effect of comorbidity on survival in the two groups. Nonrandomized data show that survival for men with a PSA greater than 10 ng/mL who received radiation versus surgery was similar.12 The complications of radiation therapy include urinary and/or fecal incontinence as well as radiation proctitis. Rectal bleeding occurs in 20% of men who receive brachytherapy and 30% who receive conformational radiation therapy.17

Androgen Suppression

Half of men diagnosed with prostate cancer receive androgen deprivation therapy.18,19 Androgen suppression is indicated initially in locally advanced disease and in recurrence. Treatment with androgen suppression results in osteoporosis, increased risk of falls, increased risk of fractures, and the development of frailty syndrome.18,20-22 Androgen deprivation also negatively impacts comorbidities, including diabetes mellitus and coronary artery disease.23 Treatment with neoadjuvant androgen deprivation in men who undergo radical prostatectomy does not prevent PSA progression, and one trial showed no overall and no disease-specific benefit of androgen deprivation after 6 years.12 A study with 10-year follow-up data showed that men receiving primary androgen deprivation therapy had a lower prostate cancer–specific survival, and no increased overall survival. Men with poorly differentiated cancers had an improved prostate cancer–specific survival, but no increase in overall survival.24

Watchful Waiting

In a study of outcomes after 20 years of follow-up in men with localized prostate cancer treated either with watchful waiting or androgen suppression therapy, few men with low-grade tumors died due to prostate cancer, and most men with high-grade tumors died from prostate cancer, regardless of age at diagnosis.25 To date, trials comparing radiation therapy, surgery, and watchful waiting support the use of watchful waiting in men with localized disease who have a life expectancy of less than 10 years.12

Adverse Effects of Treatment

In general, men who receive treatment for prostate cancer experience higher rates of adverse effects than those who choose watchful waiting. In men who undergo prostatectomy, 18% have moderate-to-severe urinary leakage, and 27% reported distress due to symptoms.12 Androgen deprivation causes hot flashes and gynecomastia, but causes fewer GI and genitourinary effects than radiation therapy. Late GI toxicity, especially rectal bleeding, is more common after radiation therapy, and occurs in about 40% of men who get radiation.26 Urinary side effects are more common after surgery as opposed to radiation or androgen deprivation. Sexual dysfunction is common in all three groups, with impotence rates as high as 60%. Radiation can also cause urethral strictures and hematuria.12 Androgen deprivation therapy is the most widely used treatment and is used for the treatment of systemic disease, either initially or after biochemical recurrence following localized therapy, as well as for treatment of metastatic disease. For systemic disease, androgen suppression is often continued life-long, resulting in adverse effects that men experience for many years.27

Health-related quality of life is reduced by prostate cancer as well as its treatment. Urinary and sexual symptoms are associated with a decline in functional scores, as well as other scores in quality-of-life instruments. This may be mediated by comorbidities, especially diabetes and vascular disease, as well as by socioeconomic status.28 Screening and treatment decisions contribute to anxiety, and after many years, anxiety is lower in patients who undergo surgery versus those who choose watchful waiting.29

Recurrence of Prostate Cancer

Recurrence of prostate cancer after prostatectomy or radiation can occur after long periods of time, around 10 years or longer. Approximately one-third of patients who undergo prostatectomy will have a recurrence of a high PSA within 10 years. PSA doubling time, Gleason score, and time from surgery to recurrence can all help to predict survival after recurrence. For example, men with a PSA doubling time of less than 3 months, who recur less than 3 years after surgery, and have a Gleason score of 8 or greater, have a 51% prostate cancer–specific survival after recurrence.30

Metastatic Disease

Metastatic prostate cancer is not common but is associated with a poor prognosis. One-third of men with metastatic prostate cancer will be alive in 5 years. Prostate cancer most commonly metastasizes to bone, followed by lung, liver, pleura, and adrenals.4 Men with metastatic prostate cancer may present with bony pain, lower urinary tract symptoms (such as frequency, urgency, or urinary retention), progressive renal dysfunction, or anemia and bone marrow failure.31

The initial treatment for metastatic prostate cancer is androgen suppression. Androgen suppression may be initiated immediately or upon experiencing symptoms, but there is no difference in overall survival between the early versus late initiation of treatment.32 Around 18-24 months after initiating androgen suppression therapy for metastasis, nearly all patients develop hormone refractory cancer. Advanced or metastatic hormone-refractory prostate cancer is incurable and progressive. Hormone refractory disease results in a progressive decline and death, with a median life expectancy of 6-12 months after androgen withdrawal, depending on symptoms and performance status. Recent studies with docetaxel have shown an increase in overall survival, as well as a reduction in pain and other symptoms.33

Metastatic disease frequently causes symptoms, including lower urinary tract symptoms, bone pain, fractures, spinal cord compression, renal dysfunction, and impaired quality of life. About one-half of men with metastatic disease will have symptoms that require intervention. Lower urinary tract symptoms may be treated with a transurethral resection of the prostate or with a chronic indwelling catheter. Progressive renal dysfunction due to outflow obstruction may be treated with a nephrostomy tube. Patients with symptomatic anemia may require blood transfusion, but red blood cell colony stimulating factors such as erythropoietin have limited use due to high cost-benefit ratio. Bony metastasis is treated with analgesics and bisphosphonates, and approximately 10% of patients with bony metastasis will have ongoing pain despite the use of analgesics. Bone pain due to pathologic fractures usually requires surgical fixation followed by radiation therapy. Spinal cord compression in metastatic disease is usually treated with corticosteroids and radiation therapy and is rarely managed surgically.31 

 

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The Impact of Tumor Grade and Comorbidities on Survival

Comorbidity is an important predictor of non-prostate mortality, and tumor stage and grade are important predictors of prostate cancer mortality. Most men will die from comorbid illness rather than prostate cancer. To demonstrate the impact of tumor grade, only 7% of men who have a low-grade cancer with a Gleason score between 2 and 4 die from prostate cancer. However, 53% of men with a high-grade cancer died from the disease within 10 years.2 Patients with high-risk disease or a high Gleason score are more likely to die from prostate cancer, regardless of comorbid illnesses. Even in men age 75 and older, those with high-grade prostate cancer are more likely to die from complications of prostate cancer rather than from comorbid illnesses.25 However, most men will be diagnosed with low- or intermediate-grade tumors, and thus their survival will depend on the number and severity of comorbidities.

Prostate Cancer in LTC Residents

One in seven men who were age 65 or older in 1990 will spend at least one year in a NH.34 Men in LTC settings are likely to be frail, cognitively impaired, and have comorbid illnesses. Men have a significantly higher risk of death than women in NHs.35 However, men in LTC settings are heterogeneous, and their life expectancy is influenced by many factors, including gender, age, comorbidities, and functional status. Given the advanced age of the LTC population, prostate cancer is likely very prevalent in such patients. In general, cancers that are diagnosed in patients already residing in NHs are more likely to be late or unstaged diseases, with high 3-month mortality rates after diagnosis of 48%, and low hospice use even in the presence of metastasis.6 However, prostate cancer comprises about 10% of these new cases and has not been specifically examined in LTC. The optimal strategy for the diagnosis of prostate cancer in men residing in LTC must consider the above factors that contribute to benefit, risk, cost, and consequences of screening and subsequent treatment.

Prostate Cancer and Dementia

The benefit of diagnosing early-stage prostate cancer in LTC settings is further diminished by the impact of dementia on prostate cancer mortality. More than half of NH residents have dementia.36 The presence of dementia is associated with increased cancer and noncancer mortality in men subsequently diagnosed with prostate cancer, and adjusting for stage at diagnosis has no impact on cancer mortality.37 Given the additional ethical concerns about using a screening test that may lead to more invasive diagnostic testing and psychologic distress, screening for prostate cancer may not be appropriate in men with dementia in LTC settings.

Current Recommendations for Prostate Cancer Screening

The American Urological Association (AUA) recommends getting a baseline PSA test at the age of 40 for men interested in early detection, and offering regular prostate cancer screening with a PSA and DRE for well-informed men. Although some studies had shown that the PSA and DRE together were better than either alone, one study showed that the DRE did not improve upon the PSA in the ability to detect prostate cancer. For this reason, the AUA recommendation is to screen with a PSA and a DRE, but not the DRE alone. Transrectal ultrasound is used to follow up an abnormal PSA and/or DRE in order to obtain a prostate biopsy, but there is no role for the use of transrectal ultrasound in prostate cancer screening. While acknowledging the reduced benefit of screening men with a life expectancy of less than 10 years, the AUA statement points out the need to discuss the risks and benefits of screening and diagnosis of prostate cancer, and to educate patients that diagnosis does not automatically warrant treatment.7

Considering the benefits and risks of screening for prostate cancer and of its subsequent treatment, the United States Preventive Services Task Force (USPSTF) recommends cessation of prostate cancer screening in men age 75 years and older. This roughly equates to men who have a life expectancy of less than 10 years.38 The American Cancer Society (ACS) guidelines do not recommend routine prostate cancer screening. Similar to the USPSTF guideline, the ACS suggests offering testing with a PSA and DRE annually starting at age 50 in men with at least a 10-year life expectancy.39

Prostate Cancer Screening in LTC

Given the frailty and increased mortality of the NH population, according to the USPSTF and ACS guidelines, most men in NH settings should not undergo screening for prostate cancer. Men who reside in LTC are not likely to live long enough to benefit from prostate cancer screening or treatment for localized disease. About half of 85-year-old men in LTC with one comorbid illness and loss of one activity of daily living will have a life expectancy between 1.5 and 4.9 years. This means that the healthiest 25% of 85-year-old men in LTC will live beyond 4.9 years. At 10 years, however, only 5% of all NH patients are still alive.34

The most important point relevant to LTC patients is that the stage of prostate cancer has a vanishingly small impact on survival in patients with a combination of advanced age and comorbidities. However, the diagnosis of prostate cancer can still have a major impact on quality of life, because screening for prostate cancer is usually followed by biopsies, treatments such as radiation or surgery, medications with systemic side effects, and further serial evaluations. Therefore, the benefit of screening in men with advanced age and multiple comorbidities is substantially diminished because the benefit from diagnosing prostate cancer at an early stage versus a late stage goes away, while the physical and emotional costs are high.

The potential pros of screening for prostate cancer with a PSA and DRE in younger, healthier men in order to diagnose a treatable disease at an early stage are not apparent in men residing in LTC, and are counterbalanced by the cons of following up an abnormal screening test with further examinations that may result in pain and anxiety to diagnose a disease not likely to cause symptoms or early mortality. Rather than performing routine screening, symptoms of back pain and bone pain, new-onset erectile dysfunction, or signs of spinal cord compression warrant a work-up that includes an evaluation for prostate cancer with a PSA and DRE.7 Although men who present with symptomatic cancers may have urinary difficulty or hematuria, urinary symptoms are more likely to be caused by benign hypertrophy rather than cancer.8 Men with symptoms of prostate cancer found to have an abnormal DRE and/or PSA should be referred to a urologist, radiation oncologist, or genitourinary oncologist for further evaluation when treatment for symptomatic disease is desired.

Summary and Recommendations

Prostate cancer is a common but generally indolent disease, and most men will die from comorbid illness rather than prostate cancer. Furthermore, comorbid illness has an impact on the outcomes of available therapies for prostate cancer, such that many older men will die from comorbidities and will not live long enough to benefit from therapy for prostate cancer with curative intent in the setting of localized disease. However, advanced or metastatic prostate cancer can present with symptoms that affect quality of life and may have focused treatment strategies. Thus, we recommend that men in LTC should not receive PSA or DRE screening. An appropriate approach would be to evaluate symptoms and treat symptomatic prostate cancer when it is identified. Evaluation for prostate cancer in LTC settings should be restricted to men who have suspected symptoms of prostate cancer.

Dr. Holmes is supported by a Hartford Geriatrics Health Outcomes Research Scholars Award. The authors report no relevant financial relationships.

Dr. Holmes is at The University of Texas M.D. Anderson Cancer Center, Department of General Internal Medicine, Ambulatory Treatment, and Emergency Care, Houston; and Dr. Goodwin is at The University of Texas Medical Branch, Department of Internal Medicine, and Sealy Center on Aging, Galveston.

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