40: Benign Prostatic Hyperplasia & Prostate Cancer

Disease processes involving the prostate gland are common in older men and can have a significant impact on their quality of life. The diagnostic evaluation and treatment plan of such conditions can be challenging for the primary care clinician, who must align the patients’ goals of care with the risks and benefits of the available testing and treatment options. This chapter discusses 2 common prostate issues that frequently occur in older adults: benign prostatic hyperplasia (BPH) and prostate cancer.

General Principles in Older Adults

BPH remains a common condition in older men that can lead to diminished quality of life. Based on autopsy data, the prevalence of BPH approaches 50% by the sixth decade of life and is close to 90% in men age 80 years and older. However, older men who are symptomatic from BPH underreport their symptoms to their clinicians and, therefore, are less likely to receive medical or surgical treatment for bothersome complaints.

Clinical Findings

Symptoms & Signs

When patients develop clinically significant BPH, they complain to clinicians of lower urinary tract symptoms (LUTS) such as increased urinary frequency, nocturia, urinary hesitancy, urine stream weakness, postvoid dribbling, and incomplete bladder emptying. Dysuria and hematuria are not commonly associated with BPH and may be an indication that another disease process is present.

The American Urological Association Symptom Index (AUA-SI) is a 7-item tool that health care providers can use to screen for symptomatic BPH as well as to assess a patient’s LUTS severity. Individual item scores are 0 for “not at all” to 5 for “almost always,” with a total maximum score of 35 (Table 40–1).

On physical examination, a digital rectal examination (DRE) may reveal a symmetrically enlarged prostate gland with a smooth and rubbery consistency. However, BPH may not be apparent on DRE in up to 52% of cases. Additionally, prostate size on DRE does not correlate with the severity of symptoms related to BPH. If significant urinary retention has resulted from a critically enlarged prostate gland, one may find a distended and tender bladder on palpation of the abdomen.

Laboratory Findings

There are no blood tests that confirm the presence of BPH. Though the American Urological Association (AUA) recommends obtaining a serum prostate-specific antigen (PSA) level when patients present with LUTS, it is for the purpose of identifying high PSA levels that might warrant further diagnostic work-up for prostate cancer. Although a PSA level above 2.0 ng/mL is correlated with a prostate volume greater than 40 mL in men older than age 60 years, PSA levels are not universally elevated in all cases of BPH, and other conditions, such as recent indwelling bladder catheter placement, prostatitis, and prostate cancer, can cause PSA elevations. In cases where it is necessary to determine prostate volume, ultrasound (either transabdominal or transrectal) of the prostate is the preferred imaging test. However, routine use of ultrasound or other imaging studies to diagnose BPH is currently not recommended.

Differential Diagnosis

When patients complain of LUTS, it is important to obtain additional history to augment information obtained through the AUA-SI. For example, nocturia may be caused by patients’ drinking habits prior to bedtime, as well as medications they have been instructed to take at night. Consequently, ask patients to keep a voiding diary, where they record what types of beverages they drink at what time of day, along with the times they urinate and estimates of urine volume with each void. Consider medications in the differential diagnosis, particularly if the patient is taking diuretics, medications with anticholinergic side effects that might lead to urinary retention (such as diphenhydramine), and nonprescription sympathomimetic decongestants that might exacerbate prostatic smooth muscle contraction (such as pseudoephedrine). Increased urinary frequency, urgency, and nocturia may be presenting symptoms of type 2 diabetes mellitus; if patients have a family history of diabetes and concomitant symptoms of polydipsia, polyphagia, and weight change, this may indicate new-onset diabetes rather than BPH.

If patients complain of dysuria, hematuria, fever, and chills in addition to those symptoms more commonly seen in BPH, obtain a urinalysis and urine culture to rule out UTI. Prostate cancer should be considered if patients present with systemic symptoms (such as anorexia, weight loss, and night sweats) and back pain and/or radiculopathy that might indicate bone metastases with nerve root compression. In addition, DRE may be notable for a nodular prostate, and PSA levels may be more markedly elevated in prostate cancer as compared to BPH. Prostatitis should be considered if patients complain of pain on ejaculation, the prostate is painful and edematous on palpation during DRE, and leukocytosis is seen on urinalysis. Nephrolithiasis should be considered when patients present with concomitant unilateral flank pain and gross or microscopic hematuria.

Certain historical factors, symptoms, signs, and testing results should trigger an immediate referral of the patient with LUTS to urology for further evaluation. These include a history of recurrent UTIs, underlying neurologic disease that could be associated with a primary bladder problem, a palpable bladder on exam, DRE findings that are suspicious for prostate cancer, elevated PSA levels, and hematuria.

Complications

Outlet obstruction from an enlarged prostate may lead to urinary retention, which, in turn, is associated with the development of recurrent UTIs, acute kidney failure, and chronic kidney disease. Acute urinary retention occurs in approximately 20% of cases.

Treatment

Severity of BPH symptoms should guide treatment recommendations.

Mild symptoms

If a patient’s AUA-SI score indicates symptoms of mild severity (score 0–7), counsel the patient on behavioral modifications, such as minimizing intake of caffeinated and alcoholic beverages, reducing daytime fluid intake if excessive, and eliminating nighttime fluid intake. There is no evidence to support the use of medications in this setting. Patients should also be followed periodically for worsening of symptoms (ie, watchful waiting) that might warrant medical or surgical intervention.

Moderate-to-Severe Symptoms

In addition to behavioral modifications, patients with moderately severe symptoms (AUA-SI score 7–35) who are bothered by their symptoms may benefit from medical therapy, which can be initiated by primary clinicians. α-Adrenergic blockers have been found to improve BPH symptoms significantly when compared to placebo, largely through inhibition of prostatic smooth muscle contraction that results in improved urine flow through the urethra. Although doxazosin and terazosin appear on the 2012 Beers Criteria for medications to use with caution in older patients, this warning applies to their use as primary medical therapy for hypertension and not symptomatic BPH. Orthostatic hypotension and arrhythmias are the most concerning potential adverse effects of these agents. Other side effects of note include dizziness (in up to 19% of cases), headaches, muscle weakness, nausea, and vomiting, dyspepsia, constipation, and diarrhea. When initiating these agents, start with the lowest possible dosages (doxazosin 1 mg or terazosin 1 mg at bedtime) and titrate upwards if needed for better symptom control and as tolerated by the patient. Patients and primary clinicians may prefer these older α blockers because they are inexpensive as compared to tamsulosin and alfuzosin. Tamsulosin should be initiated at 0.4 mg daily, although the dose may need to be increased to 0.8 mg to achieve symptom relief, which might result in increased cost to the patient (it is only available as a 0.4-mg capsule). The recommended and available dosage of alfuzosin is 10 mg daily. Of note, its bioavailability and serum concentrations increase by approximately 50% in the setting of stages II–IV chronic kidney disease (ie, in mild-to-severe renal impairment). Prazosin is no longer recommended for the treatment of BPH-related LUTS because of the associated high risk for adverse events.

Although there is no evidence for a causal relationship between α-blocker use and intraoperative floppy iris syndrome (IFIS), this association has been reported in the literature, with the risk being highest among patients taking tamsulosin as compared to other α blockers. Therefore, initiation of α-blocker therapy should be postponed until after any planned cataract surgeries. It is unknown whether discontinuing α-blocker therapy prior to cataract surgery is effective in preventing IFIS.

5α-Reductase inhibitors (5αRI) may be helpful in delaying progression of BPH, particularly in reducing patients’ risk for acute urinary retention and need for prostate surgery. They are most effective in patients with enlarged prostate glands (based on DRE, elevated PSA levels, and/or volume measurement obtained through ultrasound) and should only be used if this circumstance exists. However, some trials suggest that they are not as effective as doxazosin in treating LUTS in the short term. Two medications in this class are currently available: finasteride (dosed at 5 mg daily) and dutasteride (dosed at 0.5 mg daily). Of note, finasteride cannot be crushed and thus can only be given to patients who are able to swallow pills. Dutasteride has a half-life of 5 weeks; therefore, associated adverse side effects of erectile dysfunction and decreased libido may be long lasting in patients on this medication.

Additionally, long-term use (ie, greater than 4 years) of 5αRI and α-blocker combination therapy in patients with documented prostatic enlargement may be more effective than using 5αRI alone in delaying symptom progression, reducing rates of acute urinary retention, and reducing the need for prostate surgery. The 5αRI and α-blocker combinations that have been studied are finasteride with doxazosin and dutasteride with tamsulosin.

Patients may inquire about using complementary and alternative medicines (CAM) to treat BPH symptoms. Several products are currently available for over-the-counter purchase, including supplements containing saw palmetto (Serenoa repens), β-sitosterols, and stinging nettle (Urtica dioica). To date, there is insufficient high-quality evidence to support the effectiveness of these agents in reducing LUTS related to BPH.

Persistent Bothersome Lower Urinary Track Symptoms

In the event that medical therapy does not improve patients’ LUTS symptoms, they should be referred to urology for discussion of surgical interventions. Additionally, surgical therapy is indicated when patients have BPH-related renal insufficiency, recurrent UTIs, and bladder stones or gross hematuria caused by BPH. Surgical options include open prostatectomy, transurethral resection of the prostate (TURP), various laser therapies, and transurethral incision of the prostate (TUIP). The choice of which surgical approach to use will depend on the patient’s presentation, anatomy, and prostate size; the urologist’s experience with the different surgical techniques; the patient’s ability to tolerate the procedure based on the patient’s preexisting comorbid conditions; and the patient’s preferences based on the risk-to-benefit profiles of each individual surgical option. Although there are some minimally invasive therapies now available (specifically transurethral needle ablation of the prostate and transurethral microwave thermotherapy), questions exist about the durability of symptom relief following these procedures.

Prognosis

Increased mortality associated with BPH occurs only when complications arise (such as acute kidney failure or UTI) or in relation to medical or surgical therapies undertaken for the condition. The presence of BPH in itself is not associated with increased mortality.

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.

Screening

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.

Prevention

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.

Clinical Findings

Symptoms & Signs

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.

Laboratory Findings

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.

Diagnostics

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.

Treatment

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.

Advanced Prostate Cancer

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.

Complications

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.

Prognosis

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.