Elderly Man With Elevated PSA Level

A 79-year-old man has an elevated prostate-specific antigen (PSA) level(11.3 ng/mL). About 1 month earlier, when he was hospitalized for a seriousurinary tract infection (UTI), his PSA level was 13.3 ng/mL. The more recentlevel was obtained after he received antibiotic therapy for the UTI.

HISTORY
The patient has had symptoms of urinary tract obstruction for severalyears; these have recently worsened, and he now experiences nocturia 4 or 5times a night. For many years, he has had chronic obstructive pulmonary disease(COPD), associated with a smoking history of 55 pack-years; symptomsinclude a daily productive cough and dyspnea on exertion. He uses a varietyof nebulizers and theophylline.

The patient remains active and plays golf weekly. He lives at home withhis wife, who had a minor stroke several years ago. Although she has recoveredand has no major disability, she no longer drives, and her husband hasbecome the main caretaker in the household.

PHYSICAL EXAMINATION
The patient appears his stated age. There is mild expiratory wheezing inthe upper lung fields. Heart beat is regular, with an increased P₂ sound. Percussionof the bones reveals no tenderness.

LABORATORY AND IMAGING RESULTS
Results of a chemistry panel are normal. Alkaline phosphatase level is slightlyelevated at 250 U/L (normal, less than 225 U/L), but hepatic transaminase levelsare normal. Hemoglobin level is 16.2 g/dL; hematocrit is 52%; and white blood celland platelet counts are normal. Chest film findings of a low diaphragm and hyperinflationare consistent with COPD. An ECG shows a borderline P pulmonale andlarge R waves in the precordium but is otherwise normal.

Which of the following options is most appropriate for this patient?

• Perform a biopsy, and if the results are positive for prostate cancer,obtain a metastatic workup. If results of the workup are negative, proceedwith a radical prostatectomy.
• Perform a biopsy, and if the results are positive for prostate cancer,obtain a metastatic workup. If results of the workup are positive, refer thepatient to an oncologist for chemotherapy prior to any surgery.
• Proceed with a transurethral prostatic resection (TUPR) to relieve symptoms,and obtain bone studies to detect metastatic disease. Defer furthertherapy pending symptoms of metastatic disease.
• Proceed with TUPR to relieve symptoms, and obtain bone studies to detectmetastatic disease. Initiate hormonal therapy for any metastatic diseaseimmediately following the operation.

CORRECT ANSWER: C
This case illustrates the controversy that surrounds themanagement of prostate cancer generally-and thescreening for and management of prostate cancer in elderlymen specifically

Factors that favor a conservative approach. Studieshave shown that men 70 to 74 years of age can expectto live 10 or more years; thus, prostate cancer results inincreased mortality even at that age. Therefore, some expertshave recommended that such men should be offeredthe more aggressive therapies used in youngermen.¹ However, this patient is older than the men in thesestudies. Moreover, several factors lend further support toa more conservativeapproachhere. First, thepatient has clinicallysignificantCOPD and perhapseven earlypulmonary hypertension(evidencedby aslightly elevatedhemoglobin leveland hematocrit,and suspiciousfindings onECG). Thus, thisman is at significantlyincreasedrisk for perioperative complications from general anesthesia.Also, his COPD has probably compromised hislongevity. Second, the patient is his wife's caretaker; anycomplications from a surgical procedure could have a potentiallydisastrous effect at home.

Radical prostatectomy (choice A) is inappropriateon several counts. This difficult procedure requires generalanesthesia and has both short- and long-term sideeffects, including impotence and urinary incontinence,which are more common in older men.² In addition,most studies indicate that the survival benefit of this procedure,as a cure for prostate cancer, does not becomeevident until 10 or more years afterwards, in comparisonwith other therapies, such as radiation.² Thus, few centersroutinely offer radical prostatectomy to patientsolder than 70 years.

Chemotherapy for metastatic disease (choice B) is aneven less appropriate option. The record of chemotherapyfor prostate cancer is mediocre at best, and in any eventsuch treatment is only palliative. No survival benefit hasbeen demonstrated. If this patient does have occultmetastatic disease (ie, in the bones), it is asymptomatic,and few experts would recommend chemotherapy at thistime.

The data about the effectiveness of early hormonaltherapy (choice D) in this setting are conflicting. Severalstudies have shown that men without evidence of metastasisor with early metastasis live longer if they receive hormonaltherapy at the time of prostatectomy.³ However,other studies have shown that even without hormonaltherapy, the interval between the detection of surgicaland/or biochemical evidence of metastasis and the developmentof clinical metastasis is long-8 years in onestudy.⁴ This would be a long time for a man who is 79years old. Also bear in mind that this therapy is primarilypalliative and that it has side effects (eg, osteoporosis andfatigue). Although some experts might offer hormonaltherapy to this patient, its use remains controversial.

This patient's COPD and age make a 10-year lifeexpectancy conjectural, and his social situation makesany serious complications of surgery highly problematic.Thus, a conservative approach-TUPR to relieve symptomsof obstruction, and "watchful waiting"(unless resultsof bone studies are alarming)-is optimal here.

Outcome of this case. The patient underwent an uneventfulTUPR, and Gleason grade 4 prostate cancer wasfound. Results of a bone scan were normal. His PSA level6 months after surgery was 9 ng/mL and has been stable.He has resumed all his previous activities and continuesto do well at home.

References:

REFERENCES:1. Albertsen PC, Hanley JA, Gleason DF, Barry MJ. Competing risk analysis ofmen aged 55 to 74 years at diagnosis managed conservatively for clinically localizedprostate cancer. JAMA. 1998;280:975-980.
2. Ko YJ, Bubley GJ. Prostate cancer in older men. Oncology (Huntingt). 2001;15:1113-1131.
3. Messing EM, Manola, J, Sarosdy M, et al. Immediate hormonal therapy comparedwith observation after radical prostatectomy and pelvic lymphadenectomyin men with node-positive prostate cancer. N Engl J Med. 1999;341:1781-1788.
4. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progressionafter PSA elevation following radical prostatectomy. JAMA. 1999;281:1591-1597.