Since 1990 the re-ported number of

new cases of prostatecancer has tripled,from fewer than100,000 annually toan estimated 317,100

this year. The jump in incidence is large-ly the result of the introduction of tests,beginning in the late 1980s, that can sig-nal the presence of previously undetect-able cancer. By measuring the amountof a protein called prostate-specific anti-gen (PSA) in a male adult’s blood, thetests may unmask a cancerous prostatefive years or more before other symp-toms arise.

On its face, extending PSA testing toall men seems an obviously desirablegoal. As a rule, the earlier someone’scancer is detected, the better the per-son’s prospects for cure. Andthis cancer now takes a hightoll: more than 40,000 menwill die of it in 1996, mak-ing it the second leadingcause of cancer death (afterlung cancer) and the sixthleading cause of death over-all among American men.Prostate cancer is often char-acterized as a disease thatolder men die with ratherthan of (because it oftenprogresses more slowly thanother cancers do). Its inci-dence, mortality rate andmean age at diagnosis are infact very similar to breastcancer statistics. Further-more, once prostate cancerreaches an advanced stage,there is no effective therapy.

Yet many physicians, poli-cymakers and patients are questioningthe wisdom of widespread PSA screen-ing. In addition to the billions of dollarsrequired for universal screening and sub-sequent potential treatment, they aredeterred by the fact that no one actuallyknows whether such testing would ben-efit the average man or reduce overallmortality for the population as a whole.

The favorable arguments are many.PSA is an effective screening tool: biop-sies reveal cancer in about a third ofmen with elevated PSA levels. Screeningclearly detects many tumors that would

be missed by the traditional rectal ex-amination, in which a physician feelsthe prostate. In addition, cancers detect-ed by PSA screening are almost alwayslarger and more aggressive than the in-dolent tumors found incidentally at au-topsy in men who die of other causes.

PSA testing also often detects cancerat an early stage, when it is most likelyto respond to treatment. Before PSA test-ing was introduced, two thirds of pros-tate cancers found had already spreadbeyond the prostate, making them es-sentially incurable. Most patients faceda choice between hormone therapy andremoval of the testes, neither of whichconferred more than a few years of sur-vival. Today nearly two thirds of pros-tate cancers detected in screening pro-grams and treated surgically are confinedto the gland and can thus be eradicated

by surgery or radiation.For such reasons, both the

American Cancer Society andthe American Urological As-sociation currently recom-mend that healthy men olderthan 50 years who have alife expectancy of at least 10years undergo both rectalexamination and PSA testingannually. Men at high riskfor prostate cancer, includingAfrican-Americans (whosediet and average health carestatus appear to predisposethem to the disease) andthose with a family historyof the disease, should begintesting at age 40.

At the same time, there isno unequivocal evidence thatearly detection through peri-odic screening with PSA mea-

surements (or rectal examinations, forthat matter) in fact reduces the chancesof death from prostate cancer.

Some critics point to mortality figuresas evidence that PSA testing does notsave lives. They note that the enormousrise in early detection through PSA hasnot yielded a substantial change in deathrates during the past decade. But thisargument does not hold water. Becauseprostate cancer often progresses moreslowly than other cancers, taking 10years or more to become deadly, de-creases in death rates would not be ex-

pected to show up for many years. IfPSA screening does influence mortality,the effect probably will not be notice-able until after the turn of the century.

Other concerns about the value of PSAscreening arise from the perhaps sur-prising fact that most growths of can-cerous cells within the prostate do notlead to serious illness or death. A thirdof men over age 50 harbor some formof the cancer, but only between 6 and10 percent will acquire the type likelyto lead to death or disability. And onlyabout 3 percent eventually die of it.

Most prostate tumors are tiny andconsist of well-differentiated or moder-ately differentiated cells; they are unlike-ly to cause clinical disease within the re-maining life expectancy of a man olderthan 70 years. A small proportion arelarge and contain highly irregular cellsthat metastasize early, killing patientswithin a few years of their spread to oth-er parts of the body. Unfortunately forsimple medical decision making, mostmalignancies detected today, especiallyby means of PSA tests, fall into an inter-mediate range whose variable naturalhistory makes it difficult to distinguishthose likely to progress rapidly fromthose that can safely be left alone.

Computer models of the value of ear-ly detection and treatment suggest thatscreening millions of men may offer lit-tle overall benefit to society in terms ofeither improved health or allocation ofscarce medical resources. Critics worryabout unnecessary costs and distress topatients. The two thirds of men who un-dergo biopsy as a result of elevated PSAonly to learn that they have no appar-ent cancer are exposed to unwarrantedstress and anxiety as well as some riskof infection and bleeding. To these neg-atives must be added the hazards oftreatment (which can include urinaryincontinence and impotence) for a fur-ther minority whose cancer would oth-erwise have remained undetected for therest of their lives. The widespread use ofPSA testing to screen men with no symp-toms of prostate cancer, then, couldmean that many tumors that would pre-viously have had no effect on people’slives will now be detected and treatedat substantial costs in dollars and in suf-fering. Only time will tell whether thecount of significant yet treatable cancers

114 Scientific American September 1996

Current Controversy

Does Screening for Prostate Cancer Make Sense?

Does Screening for Prostate Cancer Make Sense?

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uncovered—and the resulting sur-vival benefits—outweighs these costs.

Assuming that a prostate cancer,once detected, is both dangerous andstill potentially curable, there remainsconsiderable controversy about howto treat it. The three best understoodalternatives are “watchful waiting,” ex-ternal irradiation and surgical prosta-tectomy. The choice of treatment forany given case is a divisive issue forboth physician and patient. Each has itspros and cons, and there is no consen-sus on which is best.

Radical prostatectomy has been usedto treat prostate cancer since 1903. Since1984 the number of operations per-formed each year has increased morethan sixfold, with an estimated 160,000done in 1995. Its major advantage isthat if the disease is truly localized, can-cerous cells can be removed completely,effectively curing the patient in as manyas 70 percent of cases. More than fourout of five patients who have no detect-able PSA five years after surgery nevershow signs of recurrence.

The immediate price a patient paysfor this effectiveness is a major opera-tion with a stay in the hospital and anextended recovery. Longer-term side ef-fects may include several months of uri-nary stress incontinence (with a chanceof permanent incontinence between 3and 5 percent) and six months to a yearof erectile impotence (with a chance ofpermanent loss between 30 and 50 per-cent). The rate at which function returns(if it does) depends on the patient’s age,previous state of sexual function andthe extent of the operation to remove thecancer. Medical centers that have exten-sive experience with prostate surgeryalso tend to produce better results.

External irradiation can eliminate thecancer for the remaining life of the pa-tient while avoiding some of the imme-diate postoperative side effects. It hasits own risks, including diarrhea fromradiation-induced inflammation of therectum in the short term and chronicradiation injury to the rectum and grad-ual decline of sexual function over thelong term. Newer conformal radiationtherapy employs carefully shaped beamsto maximize the destruction of cancercells while limiting damage to surround-ing tissue. The technique reduces the riskof bowel damage to about one in 100and that of impotence to about one inthree. The National Cancer Institute’s

consensus conference on prostate cancer,held in 1987, concluded that the sur-vival rates for surgery and for radiationwere indistinguishable at both five and10 years after treatment.

Watchful waiting, the most conserva-tive option, avoids treatment-relatedrisks, but it subjects a man to constantanxiety about progression of his cancerand the possibility of a protracted, pain-ful death. Such conservative treatmentdoes not imply postponing therapy butrather a deliberate decision to forgo at-tempts to cure the cancer in the beliefthat a patient may well die of old age or

some other cause before the malignan-cy leads to debility or death. Such pa-tients should expect to need palliativetreatment, including hormones or radio-therapy, if the cancer progresses. Somestudies have suggested that no treatmentresults in survival rates equal to those ofsurgery or of radiation, but those stud-ies all suffer from flaws that make theminconclusive [see “The Dilemmas ofProstate Cancer,” by Marc B. Garnick;Scientific American, April 1994].

Cancerous prostate tissue can also betreated by cryotherapy (insertion of aprobe cooled with liquid nitrogen) orinterstitial seed implantation, whichemploys tiny radioactive pellets whoseintense radiation does not penetrate farenough to reach other tissue. Not enough

is known thus far about the side ef-fects or success rates of either meth-od to permit comparison with estab-lished therapies.

PSA testing has revolutionized ourunderstanding of prostate cancer and

led to a dramatic increase in its detec-tion. As a result, prostate cancers arebeing detected far earlier than before, ata time when most cancers can be treat-ed with a high probability of cure. Nev-ertheless, such screening, and the treat-ment of tumors once detected, remainsamong the most controversial subjectsin medicine.

Appropriate studies to determine thevalue of PSA testing in reducing theoverall rate of death from prostate can-cer—or in extending life in general (giv-en that so many prostate patients die ofother causes)—have simply not been

done. Some large, long-term random-ized trials and studies of easily trackedpopulations are now under way, includ-ing the NCI’s Prostate, Lung, Colon andOvarian Cancer Screening Trial. Evenso, results will not be available for atleast 10 years. Until then, men must de-cide for themselves whether the poten-tial life-extending benefits of PSA screen-ing and treatment outweigh the risks.

GERALD E. HANKS AND PETERT. SCARDINO specialize in prostatecancer research. Hanks is chair of thedepartment of radiation oncology atthe Fox Chase Cancer Center in Phila-delphia. Scardino is chair of the depart-ment of urology at the Baylor Collegeof Medicine in Houston.

Does Screening for Prostate Cancer Make Sense? Scientific American September 1996 115

The PSA test is in wide use.Should it be?

CLINICALLY UNIMPORTANT (80%)

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SMALL PERCENTAGE of the estimated eight million American men who have can-cerous cells in their prostate will be harmed by the disease. Of the cancers that could af-fect health, only about 6 percent are found by rectal examinations. Although critics ofPSA screening worry that it will catch mostly insignificant or untreatable cancers, it ap-pears to be detecting early, treatable ones instead ( green outline).

Copyright 1996 Scientific American, Inc.