General Principles in Older Adults
Prostate cancer is the most common nonskin malignancy in men. More than 2 million men are currently living with the disease, and a projected 240,000 will be diagnosed in 2012. It is an especially important disease process in the older adult population given that the incidence and mortality rises steadily with age. The Surveillance Epidemiology and End Results (SEER) database estimates that from 2005–2009, 58% of those diagnosed with and 90% of those who died from prostate cancer were 65 years or older.
The prognosis of prostate cancer is largely based on the histologic severity and tumor burden at the time of diagnosis. Current screening modalities, including serum PSA and DRE, are not reliable in predicting associated morbidity and mortality of prostate cancer, thus leading to overdetection. This, coupled with a prostate cancer-specific 5-year survival rate of 99%, has led to mounting controversy among expert panels on general screening recommendations for average-risk men. Even more complex is how to approach the older adult patient with a large burden of competing comorbidities that will likely result in death prior to progression of the prostate cancer itself.
Both the incidence and prevalence of prostate cancer has increased since 1986 when the FDA approved the use of serum PSA testing, which has allowed diagnosis of prostate cancer in its earliest stages. The SEER estimates a 75% reduction in metastatic presentation of disease and a 42% reduction in prostate cancer-specific mortality associated with the widespread use of PSA screening.
However, an elevated PSA does not always confirm the diagnosis of prostate cancer. Other causes of prostatic cell hypertrophy, such as BPH and prostatitis, can present with elevations of PSA. Thus an elevated PSA may turn out to be a false-positive result, causing anxiety for the patient and the pursuit of unnecessary invasive diagnostic testing, such as prostate biopsy. Diagnostic testing also can lead to considerable adverse side effects (see “Diagnostics” below).
Expert panels disagree on the necessity and frequency of prostate cancer screening in all age groups. The United States Preventative Services Task Force (USPSTF) released guidelines in 2012 recommending against PSA screening in the general U.S. population, stating that the potential harms outweighed the risk of not screening. In contrast, the AUA and American Cancer Society (ACS) urge that providers offer screening to appropriate patients while engaging them in discussions about risks versus benefits of such screening. If there is then an informed decision by the patient to pursue PSA and DRE screening, after careful consideration of the potential risks and benefits of screening and diagnostic work-up for abnormal screening results, it should be offered. The AUA later released the following statement in response to the USPSTF’s current recommendation: “it is inappropriate and irresponsible to issue a blanket statement against PSA testing, particularly for at-risk populations, such as African American men.”
The majority of expert panels agree that the overall health status of an individual must be incorporated into the decision to screen. Those average-risk, asymptomatic patients with a life expectancy of less than 10 years will likely not benefit from routine screening. If the health care provider believes that a patient would not be an appropriate candidate for treatment if prostate cancer is detected, screening should not be offered. Thus, an individualized approach to prostate cancer screening must be adopted by health care providers. One must weigh the risks, benefits, and current uncertainties of scientific evidence, alongside the patient’s preferences, estimated life expectancy, and potential effects of treatment on the patient’s quality of life. See Chapter 8, “Prevention & Health Promotion,” for a comprehensive approach to screening decision making in the older patient.
Testosterone plays a significant role in prostate cancer. Knowing this, the National Cancer Institute launched the double-blind, placebo-controlled Prostate Cancer Prevention Trial (PCPT) to study the effects of the 5αRI, finasteride, on the development of prostate cancer. The study was stopped prematurely when significantly fewer men in the treatment arm developed prostate cancer. However, it was later determined that survival was similar for both treatment and control groups, with the predominance of prevented cases found to be of low histologic tumor grade. Of note, high-grade tumors were more common in the treatment group. This result raised questions about whether finasteride could in fact provoke progression of histologic changes. There have been ongoing investigations to further explain this finding.
Prostate cancer in its earlier stages is largely asymptomatic. As it becomes more advanced, LUTS can develop, including urinary urgency, frequency, hesitancy, and nocturia. Prostate cancer can also present as new-onset erectile dysfunction, or less frequently with hematuria or hematospermia, which is presence of blood in the urine or semen. A small number of patients may present when the cancer has already metastasized to distant sites. The most common site is bone, presenting with pain or a pathologic fracture.
On physical exam, prostate cancer can be detected through abnormalities on the DRE. These changes include asymmetry, distinct areas of induration, and frank nodules on the prostate gland. However, a negative DRE does not completely rule out prostate cancer, as only the posterior and lateral anatomy of the prostate gland are easily obtained digitally.
Elevations in serum PSA can be associated with prostate cancer but also frequently occur in benign conditions such as BPH. A general rule is that the higher the PSA, the higher the likelihood of detecting cancer on subsequent biopsy. Biopsy is usually recommended if PSA levels are greater than 10 ng/mL. For intermediate levels (PSA between 4 and 10 ng/mL), biopsy will be considered for most older men. However, only 20% of these biopsies will be positive for prostate cancer. Studies that have focused on using age-specific PSA reference ranges, PSA velocity, and free-PSA levels to assist in risk stratifying these intermediate PSA levels have largely failed to show superiority in predicting positive biopsy results. Recommendations for PSA levels less than 4 ng/mL are even less clear. There are a considerable number of patients diagnosed with prostate cancer whose PSA levels fall in the 2–4 ng/mL range. In the PCPT trial, 20% of localized cancers found on biopsy had serum PSAs between 2.6 and 3.9 ng/mL. Men can also experience fluctuations in their serum PSA levels, and thus confirmation of an abnormal PSA is advised prior to biopsy.
A histologic biopsy is required to confirm the diagnosis of prostate cancer after an abnormal PSA or DRE is found. Biopsies are most commonly obtained transrectally, guided with transrectal ultrasonography (TRUS) to increase accuracy. Alternatively, transperineal or transurethral approaches can be used if the transrectal approach is contraindicated. Obtaining a biopsy is a relatively quick and readily available office procedure, but it can have substantial associated morbidities. These include pain, bleeding in the form of hematuria or hematospermia, infection, urinary obstruction, and the potential psychological trauma of a positive result that may not require treatment. Given that approximately 75% of biopsies return negative, candidates must be selected carefully with the assistance of an experienced urologist.
Evidence for the most effective prostate cancer treatments in older adults is lacking. This population of patients is largely excluded from current therapeutic trials. Biopsy results, along with TNM (tumor, node, metastasis) and clinical staging, will guide the selection of initial therapy. Equally important to treatment selection is balancing a patient’s stated goals and preferences with the risks and benefits of each therapeutic option being considered. Involvement of an interdisciplinary team, including the primary care provider, oncologist, and urologist, will allow formulation of the most comprehensive, patient-centered treatment plan.
Localized Prostate Cancer
For localized, organ-confined prostate cancer, the goal of therapy is to balance the risk of death and morbidity with adverse effects that often occur with treatment. The decision on which treatment approach is most appropriate to pursue requires consideration of more than just the patient’s chronologic age. It should include the incorporation of the older adult’s performance status, comorbidity burden, nutritional status, social supports, and values and preferences.
Definitive treatment options include surgical resection through radical prostatectomy (RP) and radiation via external beam radiation therapy (EBRT) or brachytherapy. With recent advancements in technology, RP and EBRT have resulted in similar disease-specific and overall mortality rates. There are currently no randomized controlled trials comparing brachytherapy to RP or EBRT; therefore, it should be used in carefully selected patients with amenable anatomy.
Because 90% of prostate cancers are clinically localized to the prostate gland and carry a low risk for progression, observation through active surveillance or watchful waiting are also options for the appropriate low-risk patient. The goal of active surveillance is to monitor closely with PSA measurement and biopsy. Curative treatment is only pursued if disease progression is suspected. In contrast, watchful waiting entails close monitoring for the development of symptoms related to the prostate cancer, with palliative treatments offered if these occur. Watchful waiting is most commonly utilized as an option in the older adult patient with a high comorbidity burden. Observation management, in general, is more frequently chosen by men older than 75 years than in younger cohorts.
Androgen deprivation therapy (ADT) alone is not considered standard treatment of localized prostate cancer due to studies suggesting an associated shortened survival and increased mortality. It does still play a role as adjuvant therapy in locally advanced disease.
Treatment of advanced prostate cancer in older adults should largely focus on the promotion of quality of life. Although only approximately 5% of prostate cancers now present initially with metastasis, the symptom burden of these patients can be quite severe. ADT is considered first-line treatment for hormone positive cancers. This involves either surgical castration through bilateral orchiectomy or chemical castration often with gonadotropin-releasing hormone (GnRH) agonists and antiandrogens.
Castrate-resistant prostate cancer in a man with optimal health and functional status is generally treated with the first-line chemotherapeutic regimen of docetaxel and prednisone. The frequency and dosing of this regimen can be altered based on the patient’s response to therapy, including how well the patient tolerates associated side effects. For those patients who have severe symptom burden and are castrate-resistant, palliative options are also available. Use of analgesics, local radiation therapy, and bisphosphonates are helpful in treating symptoms associated with bone metastases. Radiation therapy has also been shown to be beneficial for relieving the symptom burden associated with pelvic disease.
Older men have higher surgical complication rates with RP. Urinary incontinence and erectile dysfunction are quite common and result from urinary sphincter and penile nerve damage, respectively. Nerve-sparing procedures have improved impotence rates, which have been as high as 90% in patients who underwent traditional RP. Urinary leakage has been shown to be more common with RP than other methods of treatment, affecting up to 35% of patients.
Gastrointestinal and genitourinary symptoms are the most common adverse effects of localized radiation therapy (RT). Some studies suggest that older patients may develop side effects earlier in treatment, although comorbidity burden is also thought to play an important role. Bowel urgency is more common with RT than in other treatments, but still only affects 3% of recipients long-term.
ADT therapy for the treatment of advanced prostate cancer also has several potential complications, including osteoporosis and fractures, metabolic syndrome, diabetes, and cardiovascular disease. Men also report experiencing vasomotor symptoms, gynecomastia, testicular atrophy, fatigue, and depression as a result of treatment. With such an extensive side-effect profile, the prescribing provider must consider the potential interactions with already present underlying comorbidities, as these may be exacerbated during treatment.
Sexual dysfunction is a common adverse effect that can result from all treatment options, with incidence rates between <5% and 60%. This potential adverse outcome should be discussed with patients prior to initiation of therapy as quality of life can be significantly compromised when it occurs.
A larger number of men who are diagnosed in or after their seventh decade of life die of prostate cancer than younger populations. This is especially true if a more advanced, higher grade cancer is present at the time of diagnosis. Still, in observational studies, prostate cancer-specific and overall survival rates remain quite high in older adults, with competing comorbidities more commonly the cause of mortality.
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