Treating Prostate Cancer

Transcription

1 CHAPTER 4 Treting Prostte Cncer here is controversy bout the optiml tretment for cliniclly loclized prostte cncer (i.e., cncer tht ppers not to hve spred beyond the prostte bsed on informtion vilble without performing surgery). 1 In the United Sttes, the preference is for ggressive tretment, with urologists generlly preferring rdicl prosttectomy (203, 318). However, recent reserch hs reveled considerble vribility in stge-specific tretments ctully dministered (219, 238, 247). In other developed countries, urologists hve tended to be more conservtive regrding both erly detection (78, 302, 303) nd tretment (5, 175, 364). Although observtionl studies exist to determine the outcomes of men who receive different tretments nd to mesure their risks of dverse outcomes, few well-designed trils exist to determine whether observed outcomes re ctully the result of the tretment or due to some other uncontrolled nd unmesured fctor. As shown in chpter 5, this uncertinty bout tretment effectiveness is the gretest impediment to evluting the cost-effectiveness of potentil Medicre prostte screening benefit. STRATEGIES TO DETERMINE CANCER STAGE One problem with current strtegies for erly detection of prostte cncer is tht screening will detect some cncers tht re not destined to cuse morbidity or mortlity nd do not need tretment, s well s some cncers tht hve lredy spred through the prostte cpsule nd re less likely to be cured or slowed by tretment. Unfortuntely, mny ptients my need to undergo surgicl stging procedure such s pelvic lymphdenectomy, or even rdicl prosttectomy itself, to estblish the true stge of their cncer. Better, less invsive stging tests might llow physicins to withhold tretment from ptients unlikely to benefit, spring both the risks nd costs of these procedures. In terms of determining preopertively whether cncers re likely to be insignificnt (which this bckground pper defines s well-differentited nd less thn 0.5 ml in volume), clinicins hve developed some lgorithms using dt from systemtic biopsies, nd if necessry, rebiopsies (338). Unfortuntely, however, other investigtors hve documented tht these lgorithms 1 As discussed in the preceding chpters, unless otherwise indicted, cncers tht re confined within the prostte, less thn 0.5 ml in volume, nd well differentited re ssumed not to pose ny thret to ptient s helth nd would not require tretment unless they grow or chnge in grde.

2 34 COSTS AND EFFECTIVENESS OF PROSTATE CANCER SCREENING IN ELDERLY MEN predict incorrectly in qurter to third of cses (98, 191, 192). As fr s predicting preopertively which tumors hve spred to other prts of the body, detection of metstsis to bone by using rdiogrphic bone scns is reltively strightforwrd, nd lgorithms do exist to help identify low-risk subsets of men in whom bone scns re unlikely to be helpful (84, 357). However, the use of other dignostic technologies (e.g., computerized tomogrphy (CT), mgnetic resonnce imging (MRI), trnsrectl ultrsound (TRUS)) hve not yet replced opertive pthologicl exmintions to determine if the cncer hs spred to the pelvic lymph nodes (76, 164, 281) or to determine if the cncer is extrcpsulr (97, 137, 285). Models tht use the results of multiple tests to ssess the probbility of orgn confinement nd lymph node involvement lso result in substntil misclssifiction rtes for most ptient groups (1, 191, 192, 267, 283, 369). While better stging techniques, such s moleculr stging strtegies currently under ctive investigtion (185), my llow better prediction of which tumors re likely to be dngerous enough to threten ptient s longevity but still potentilly curble, selective tretment of only those tumors most likely to benefit my still be prcticlly difficult. As shown lter in this chpter, evidence estblishing the effectiveness of tretment is currently wek. Once clinicin finds cncer, in the bsence of dt tht there is not t lest some net benefit from treting even pprently inconsequentil or unconfined cncers, ptients nd physicins my hve difficulty in forgoing therpy, even when the expected net benefits re clerly less thn for other types of cncers. Mny ptients with negtive bone scns undergo dissection of the pelvic lymph nodes to determine if the cncer hs spred in the region of the prostte prior to rdicl prosttectomy, one type of tretment with curtive intent. 2 Most clinicins would not proceed with rdicl prosttectomy in light of the discovery of involved pelvic nodes, lthough minority feel tht ggressive surgicl tretment of node positive disese improves outcomes (254, 375). Recently, some urologists hve begun to question the need for pelvic lymph node exmintion prior to rdicl prosttectomy mong men with better differentited tumors, or in men with lower prostte-specific ntigen (PSA) vlues (38, 102, 126, 138). Another new strtegy sometimes employed before rdicl prosttectomy is the use of hormonl drugs to decrese the likelihood tht the cncer is found to extend beyond the outside of the prostte cpsule or beyond the surfce of the surgiclly removed specimen (known s surgicl mrgin positivity). Controversy exists bout whether this tretment (known s ndrogen bltion therpy) ctully cuses shrinking of the tumor (regression) s opposed to only decresing PSA levels (223, 259, 321). Although recently presented clinicl tril suggests tht preopertive ndrogen bltion therpy ctully does cuse some regression (202), there is no evidence such tretment improves ptient outcomes with prolonged followup. THE EFFECTIVENESS OF TREATMENT This chpter exmines three strtegies for treting prostte cncer: 1) expectnt mngement (or wtchful 2 This exmintion cn be done s trditionl, open surgicl procedure or less invsively using lproscope tht requires only smll incision (188, 290, 304). It cn be done s seprte procedure, or s the first stge of combined pelvic lymph node exmintion nd rdicl prosttectomy.

3 CHAPTER 4 TREATING PROSTATE CANCER 35 witing ), 2) rdition therpy, nd 3) rdicl prosttectomy. Expectnt Mngement Expectnt mngement, commonly used strtegy for cliniclly loclized cncer worldwide (367), cn tke two bsic forms: 1) only monitoring the ptient for symptoms relted to cncer progression nd treting these symptoms s necessry or 2) monitoring for disese progression nd ttempting cure with rdition tretment or prosttectomy in tht circumstnce. Even in the United Sttes, where the pproch to prostte cncer is much more ggressive, 1990 study by the Americn College of Surgeons Commission on Cncer found tht lmost two-thirds of Stge A cncers were not ctively treted (238). Mny men with prostte cncer treted expectntly will hve evidence of locl progression by digitl rectl exmintion (DRE) over time (342). Locl progression of prostte cncer cn cuse symptoms from bldder outlet obstruction or invsion of surrounding tissues. Bldder outlet obstruction cn be treted mechniclly (by trnsrectl resection of the prostte (TURP) 3 or, less commonly, stenting). Tretment involving deprivtion of the mle hormone testosterone (n ndrogen) is often used s prt of n expectnt mngement therpy when the disese becomes symptomtic (168) or, more recently, for evidence of cncer progression in symptomtic men. 4 Clinicins cn ccomplish ndrogen deprivtion therpy by orchiectomy (surgicl removl of the testes) or by medicl mens with other hormones or drugs (301). The ltter option is more common despite considerbly higher costs nd the risk of ptient noncomplince, t lest prtilly becuse of ptient preference (53, 65, 311). 5 Although the initil response to hormonl therpy for dvnced prostte cncer is often grtifying, it is lso frequently short-lived, with the results of subsequent chemotherpy generlly disppointing (94, 108). Wht Is the Effect of Expectnt Mngement? Although the outcomes of expectnt mngement hve been studied round the world (3, 4, 114, 135, 175, 176, 249), few investigtors in the United Sttes hve done so (178, 366). A number of cse series of men with cliniclly loclized prostte cncer in wtchful witing strtegies hve been reported from round the world. As shown in tble 4-1, recent structured literture review nd synthesis of 23 nonexperimentl studies showed tht receiving expectnt mngement for loclized prostte cncer hd rtes of metstsis nd deth no different from rdicl prosttectomy nd lower thn rdition therpy (362). However, these comprisons re inferior to wellcontrolled, experimentl results (333, 362). This literture synthesis hs been criticized for the inclusion of series describing predominntly the outcomes of erly, inconsequentil Stge T1/A1 cncers, nd for including series using erly ndrogen deprivtion therpy (132, 360). In ddition, ptients receiving rdition therpy hd more poorly differentited ptients thn those receiving other tretment options. 3 TURP does not seem to hve n unfvorble impct on the prognosis of prostte cncer (372). 4 The effect of erly ndrogen deprivtion on the nturl history of cliniclly loclized prostte cncer is not well defined; some nonexperimentl studies demonstrted little effect (23, 114). 5 Recently, clinicins hve incresingly used combintion therpy involving two gents, GnRH gonist nd n ndrogen blocker (flutmide), with some evidence from clinicl trils tht this pproch increses medin survivl time to degree (94, 108).

4 36 COSTS AND EFFECTIVENESS OF PROSTATE CANCER SCREENING IN ELDERLY MEN TABLE 4-1: PATIENT CHARACTERISTICS AND OUTCOMES OF LOCALIZED PROSTATE CANCER TREATMENT Wtchful witing Rdition therpy Rdicl prosttectomy Medin (CI) n Medin (CI) n Medin (CI) n Ptient chrcteristics Age (69-73) 27 (64-66) 49 (61-64) 33 Percent of cncers poorly differentited (6-11) 19 (13-24) 45 (6-25) 22 Outcomes Annul mortlity rte All cuses ( ) 27 ( ) 45 ( ) 27 Cncer-specific ( ) 23 ( ) 22 ( ) 23 Metsttic rte ( ) 15 ( ) 17 ( ) 18 KEY: CI = 95% confidence intervl; n = number of studies, which vries since not ll studies supply ll dt of interest. SOURCE: Office of Technology Assessment, Dt from J.H. Wsson, C.C. Cushmn, R.C. Bruskewitz, et l, A Structured Literture Review of Tretment for Loclized Prostte Cncer, Archives of Fmily Medicine 2: , A literture synthesis of seven studies (586 ptients) of outcomes of men with plpble, cliniclly loclized cncers (Stge T2) reported since 1980 yielded rtes of metstsis, overll mortlity, nd prostte cncer-specific mortlity higher thn those presented in the Wsson review described bove (6). However, one would expect these higher rtes in n nlysis restricted to plpble cncers. Only two studies provided dt on cncer-specific survivl t 10 yers mong men treted expectntly with men of 84 percent. In this nlysis, the results of studies reporting outcomes of rdicl prosttectomy were better, while studies reporting outcomes for rdition therpy were worse. One of these expectnt mngement studies enrolled men with loclized prostte cncer from welldefined geogrphic re in Sweden between 1977 nd 1984 nd hs n unusully long durtion of followup (175, 176, 177). It excluded men with modertely or poorly differentited cncer or few men receiving curtive tretment, leving smple of 223 with men ge of 72. At 12.5 yers of verge followup, there hve been 23 prostte cncer deths in the cohort (10 percent), nd 148 deths from other cuses (66 percent). Ten-yer metstsis-free survivl (corrected for deths from other cuses) ws 83 percent. Tumor grde ws the dominnt predictor of prognosis. 6 6 Although this study hs been criticized for enrolling too mny older men nd too mny with insignificnt cncers discovered during TURP nd for hving insufficient followup to detect lte upsurge in hzrd of prostte cncer deth, neither ge nor stge (controlling for grde) ws n independent predictor of the prostte cncer deth rte in this study. In ddition, the study s T0l tumors ( unique stge different from T1 or A1) included tumors encompssing up to 25 percent of the volume of the TURP specimen (s opposed to up to 5 percent for T1 or A1 tumors in the United Sttes), nd there hs been no increse in hzrd rte noted with followup to 12.5 yers. Moreover, subset nlysis for men who would be considered cndidtes for rdicl prosttectomy yielded similr results. Concerns hve lso been rised bout identifiction of prostte cncer by mens of spirtion cytology, s ws generlly the mode of dignosis in this study (214, 296); however, this method hd similr results to core biopsy in one Scndinvin study (358).

5 CHAPTER 4 TREATING PROSTATE CANCER 37 Another recent study with long-term followup showed similr results. It presented dt from men dignosed with cliniclly loclized prostte cncer in Connecticut between 1971 nd 1980, nd treted with immedite or delyed hormonl therpy when necessry. Agin, grde, but not ge, predicted cncer-specific survivl. For men over 65, cuse-specific 15-yer survivls were: well differentited, 82 to 93 percent; modertely differentited, 67 to 78 percent; nd poorly differentited, 46 to 53 percent (194). Chodk nd collegues hve recently conducted met-nlysis including 828 men (men ge 70) enrolled in expectnt mngement studies from six centers with 10-yer djusted cncer survivl rtes: well differentited, 87 percent; modertely differentited, 87 percent; nd poorly differentited, 34 percent (82, 83). Grde ws once gin the dominnt independent determinnt of the rte of prostte cncer mortlity. The predicted metstsis-free survivl t 10 yers ws lower thn the survivl sttistics would indicte: 81, 58, nd 26 percent for well, modertely, nd poorly differentited disese, respectively. 7 The Risks of Expectnt Mngement The risks of expectnt mngement for cliniclly loclized cncer include ny higher rte of the development of metstses nd prostte cncer-specific mortlity tht this strtegy imposes over nd bove the rtes seen with ctive tretment. 8 The mgnitude of these dded risks, if ny, hs not been defined. More clerly, men mnged expectntly hve incresed risks of locl cncer progression compred with men treted with rdicl prosttectomy; however, the clinicl significnce nd qulity-of-life implictions of locl cncer progression hve not been well studied (343). Johnsson reported tht 22 percent of the men in his study developed evidence of progression by DRE to Stge T3 over 10 yers; however, he recently reported tht in only six cses were locl problems substntil nd resistnt to tretment (176). 9 Rdition Therpy Rdition therpy dministered for cure (lso known s rdiotherpy) usully involves x-rys from n externl source delivered in mximl doses to the prostte, lesser doses to the seminl vesicle (locted bove the prostte), nd miniml rdition to the smll bowel, rectum, nl cnl, nd urethr (270). Adjustments re mde in the dose nd trgets bsed on the specific tumor nd host. Much less commonly, rdioctive seeds re plced in the prostte s primry therpy, or in combintion with externl bem rdiotherpy, to increse the dose delivered to the prostte while better protecting nerby tissues. Ptients usully receive externl bem rdiotherpy in five weekdy tretments over six or seven weeks (20). Reserch is ctively underwy to identify new methods of rdiotherpy, such s three-dimensionl conforml therpy, tht my void underdosing the prostte while more effectively excluding surrounding norml tissues, reducing the ssocited risks (209). The reltively little ttention given to rdition therpy in the recently published literture on prostte cncer detection nd tretment my reflect the fct tht urol- 7 The reson for the discrepncy between the rte of metsttic disese nd prostte cncer mortlity, prticulrly for men with modertely differentited cncer, is not well understood; to some degree, erly detection of low burden of symptomtic metsttic disese with periodic bone scns in these series my explin some of the pprent dely between the development of metstses nd cncer deth implicit in these results (278). 8 Witing for signs of clinicl progression will result in fewer cncers being pthologiclly loclized t the time clinicins ttempt curtive tretment. 9 Thirty ptients did undergo TURP for obstructive symptoms, only bout hlf of whom hd cncer in the removed tissue (176).

6 38 COSTS AND EFFECTIVENESS OF PROSTATE CANCER SCREENING IN ELDERLY MEN ogists, who most often recommend rdicl prosttectomy for loclized prostte cncer, hve conducted these studies (362). However, s recent s 1990, study by the Americn College of Surgeons Commission on Cncer found tht rdiotherpy ws used more commonly thn rdicl prosttectomy in the United Sttes for every stge of prostte cncer (238). 10 In ddition, recent study suggested tht prostte cncer ptients in helth mintennce orgniztion settings were more likely to receive rdiotherpy rther thn surgery compred with ptients in fee-for-service settings (152). 11 How Effective Is Rdition Therpy? The effectiveness of rdiotherpy, compred with either expectnt mngement or rdicl prosttectomy, for reducing mortlity nd morbidity mong men with cliniclly loclized cncer hs not been well studied. A single rndomized clinicl tril of 97 men with Stge A2 or B cncers found significnt improvement in time-torecurrence with surgery compred with rdition, but no mortlity difference (269, 359). However, becuse mny ptients crossed-over to the other tretment fter rndomiztion nd the nlysis ws bsed on tretment given rther thn intention to tret, these conclusions my not be vlid. Although the results of only one imperfect clinicl tril re vilble, some dditionl evidence is vilble from two cohort studies 12 of ptients with cliniclly loclized cncer treted with rdiotherpy for cure -the Ptterns of Cre Studies (PCS) (161, 197) nd the Rdition Therpy Oncology Group (RTOG) study (#7706) (15). At 10 yers, overll survivl mong ptients receiving rdition ws no different thn expected survivl for ge-mtched men without cncer (63 percent in PCS nd 64 percent in RTOG). In the 1978 PCS, bout 83 percent of the 10 yer survivors hd no evidence of disese. For men with plpble, cliniclly loclized T2 cncers, overll survivl t 10 yers ws 46 percent (i.e., bout 20 percent lower thn for cncer-free men of similr ge), with bout 74 percent of the survivors clssified s disesefree (165). Rdition oncologists rgue tht, out to 10 yers, these outcomes re equivlent to rdicl prosttectomy, prticulrly given the unknown nodl sttus of the rdiotherpy ptients (87, 117, 161, 163, 165, 184, 208). In fct, for subset of men in RTOG study with negtive lymph node dissections, most of whom hd T2 cncers, cncer-specific survivl ws 86 percent fter 10 yers, with 79 percent metstsis-free survivl (162). In one of the literture reviews mentioned in the section on expectnt mngement, only one study ws found to hve strtified ptient outcomes following rdiotherpy by grde nd stge of disese (362). In ll the vilble cses of ptients treted with rdiotherpy, these men hd higher medin rtes of development of distnt metstses nd cncer- specific mortlity thn men treted with rdicl prosttectomy nd expectnt mngement, but they lso hd more men with poorly 10 Presumbly, some ptients who underwent surgicl exmintion of the pelvic lymph nodes prior to rdicl prosttectomy subsequently underwent rdiotherpy insted becuse of nodl involvement. 11 However, registry dt indicte tht for the U.S. popultion s whole, this trend reversed itself in 1991 with rdicl prosttectomy becoming the more commonly used tretment strtegy (166). 12 Cohort studies re often used to compre the outcomes of two groups of ptients similr in importnt chrcteristics other thn the outcome of interest -in this cse, tretment strtegy. Becuse of the inbility to control retrospectively for ll fctors tht might be relted to tretment choice nd outcome, the results of such study re inferior to prospectively rndomized clinicl tril.

7 CHAPTER 4 TREATING PROSTATE CANCER 39 differentited cncers thn series of either of the other tretments (tble 4-1). These nonexperimentl comprisons my lso be invlid becuse of the older ge of rdiotherpy ptients, nd the fct tht ptients with lymph node involvement re included in rdiotherpy series but excluded from surgicl series. Mny urologists worry tht evidence of residul cncer in mny men following rdiotherpy ugurs poorly for the prognosis of men treted this wy (51, 75, 183, 210, 294, 297, 327, 359). On the other hnd, rtes of biopsies fter rdiotherpy hve been lower in some recent smll series of Stge T1 nd T2 disese (cncers confined to the prostte) given rdition tretment in prticulr mnner (125), nd the prognosis for men with positive biopsies fter rdiotherpy is debted (275). Risks of Rdition Therpy Injury from rdiotherpy to the rdiosensitive tissues of the bldder nd urethr cn cuse cystitis 13 nd incontinence. Injury to the rectum cn cuse proctitis, 14 nd injury to the nerves nd blood vessels djcent to the prostte cn cuse impotence (205). Tble 4-2 provides estimtes of these risks bsed on structured review of the medicl literture published since 1981 (362). 15 This literture does not llow estimtion of the hzrds of rdiotherpy specificlly mong Medicre-ge men. However, preliminry nlysis of survey of complictions of externl bem rdiotherpy mong Medicreged men suggests tht bout 5 percent of men use pds to del with incontinence nd tht 35 percent hd noted no prtil or full erections since their tretments (27). These results compre fvorbly to published dt on the complictions of rdicl prosttectomy collected using the sme methods nd discussed below (127). Rdicl Prosttectomy The third tretment strtegy, rdicl prosttectomy, entils removing the entire prostte with the tissues tht cover it nd the seminl vesicles tht sit bove the glnd. In recent yers, modifiction of the procedure by Wlsh nd collegues nd better understnding of the ntomy of the re (50) hs llowed wider excision round the prostte, but with specil ttention to nerby nerves nd blood vessels to reduce blood loss nd post-opertive incontinence nd impotence. However, ttempts to preserve these nerves in cses of cpsulr penetrtion increses the risk of surgicl mrgin positivity 16 (267, 287). How Effective Is Rdicl Prosttectomy? Observtionl dt indicte tht men who undergo rdicl prosttectomy tend to do well with prognosis dependent on disese stge (331). Those with orgn-confined cncer hve low risk of recurrence nd norml life expectncies. For men with unconfined disese, one recent study noted loclized recurrence in 8 percent of men within five yers s opposed to metstses in 30 percent. 17 This suggests tht prosttectomy improves cncer control in the re round the prostte, even in situtions when the rte of development of metsttic disese elsewhere in the body my be unchnged (50, 248). 13 Cystitis is n inflmmtion of the bldder. 14 Proctitis is inflmmtion of the rectum. 15 As with rdicl prosttectomy, complictions from rdiotherpy my depend on the expertise of the rdiotherpist nd tretment center. While some rdition oncologists t mjor referrl centers my hve better outcomes thn reflected in tble 4-2, s reported recently by Shipley (312), ntionwide prostte cncer erly detection progrm my outstrip the cpcity of these centers. 16 Mrgin positivity refers to the discovery of cncerous tissue right up to the edge of the surgiclly removed tissue, rising the possibility tht the opertion my not hve removed ll of the cncer. 17 This is the opposite of the pttern described erlier for men who re treted by expectnt mngement.

8 40 COSTS AND EFFECTIVENESS OF PROSTATE CANCER SCREENING IN ELDERLY MEN TABLE 4-2: PERSISTENT ADVERSE OUTCOMES OF LOCALIZED PROSTATE CANCER TREATMENT (from literture published since 1981) ÁÁÁÁÁÁ Rdicl prosttectomy Externl bem rdition ÁÁÁÁÁÁ ÁÁÁÁÁÁ Mortlity Weighted men 1.1% 0.2% Smple size (number of men) ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 2.0% 0.0% Number of studies ÁÁÁÁÁÁ Any incontinence ÁÁÁÁÁÁ Weighted men 26.6% 6.1% Smple size (number of men) ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 16.0% 6.5% ÁÁÁÁÁÁ Complete incontinence ÁÁÁÁÁÁ Weighted men 6.8% 1.2% Smple size (number of men) ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 6.0% 1.0% ÁÁÁÁÁÁ Any bowel injury ÁÁÁÁÁÁ Weighted men 2.7% 11.4% Smple size (number of men) ,148.0 ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 1.5% 13.5% ÁÁÁÁ Bowel injury (requiring long-term tretment or colostomy) ÁÁÁÁ Weighted men 1.3% 2.3% Smple size (number of men) ,680.0 ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 1.0% 1.0% ÁÁÁÁ Stricture requiring long-term tretment ÁÁÁÁ Weighted men 12.4% 4.5% Smple size (number of men) ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 9.0% 2.5% ÁÁÁÁÁÁ Impotence ÁÁÁÁÁÁ Weighted men 84.6% 41.5% Smple size (number of men) ÁÁÁÁÁÁ Medin probbility ÁÁÁÁÁÁ 62.0% 44.0% ÁÁÁÁ ÁÁÁÁ Medin probbility cross reported studies. SOURCE: Office of Technology Assessment, Dt from J.H. Wsson, C.C. Cushmn, R.C. Bruskewitz, et l., A Structured Literture Review of Tretment for Loclized Prostte Cncer, Archives of Fmily Medicine 2: , 1993.

9 CHAPTER 4 TREATING PROSTATE CANCER 41 However, the ttributble benefit of rdicl prosttectomy is less cler. 18 The structured literture synthesis of prostte cncer tretment, lredy described in the discussion of expectnt mngement, found rtes of deth nd metstsis tht were not sttisticlly different for rdicl prosttectomy nd expectnt mngement (tble 4-1) (362). The good outcomes for men receiving rdicl prosttectomy noted in observtionl studies re in prt due to better preopertive stging, nd the exclusion of men whose cncer is found preopertively to hve spred to the pelvic lymph nodes. Hence, nonexperimentl comprisons of outcomes of expectnt mngement, rdition therpy, nd rdicl prosttectomy re potentilly confounded by different mixes of cncer mong these studies. Only one clinicl tril hs compred expectnt mngement nd rdicl prosttectomy directly. In Veterns Administrtion Coopertive Reserch Group (VA- CURG) clinicl tril, 61 men with cliniclly loclized prostte cncer were rndomized to rdicl prosttectomy nd 50 men to expectnt mngement; bout hlf hd cncers found t TURP nd hlf plpble cncers. After seven yers nd gin fter 15 yers, there is no sttisticlly significnt difference in survivl between the two tretment strtegies (54, 147). However, the tril s smll smple size impedes detection of ny rel difference tht my exist. 19 The Risks of Prosttectomy As indicted in tble 4-2, Wsson s synthesis of the medicl literture since 1981 indictes tht the medin risk of deth ssocited with rdicl prosttectomy itself is bout 1.1 percent; ny incontinence, 27 percent; complete incontinence, 7 percent; impotence, 85 percent (31 percent in two studies of the never-spring procedure); nd stricture (obstruction or nrrowing of the urethr) requiring long-term tretment, 12 percent. However, the definitions of dverse outcomes vry considerbly mong the studies, nd s with rdition therpy, the likelihood of these outcomes re likely to vry with the experience nd skill of the surgeon nd hospitl (50, 69, 276). On the other hnd, these my be lower-bound of the risks fced by typicl ptients since publiction bis my led to underestimtes (27). Furthermore, Medicre ptients my fce higher risks becuse of ge nd comorbidities. A recent survey tht used Medicre clims dt to choose ntionl probbility smple of men who hve received rdicl prosttectomy provides more generlizble estimtes of the risks ssocited with this procedure for Medicre beneficiries (127). 20 The results re presented in tble 4-3 nd stnd in contrst to the less frequent dverse outcomes suggested by the preliminry nlysis mentioned erlier of similr survey of Medicre-ge men (lbeit older ones) who underwent rdition therpy. Within this cohort of men over 65, the risk of these complictions ws not relted to ge t surgery. FOLLOWUP TREATMENT AFTER CURATIVE THERAPY After initil tretment by rdition or rdicl prosttectomy, clinicins often consider dditionl therpy if 18 The ttributble benefit is tht portion of the totl observed benefit in the treted popultion (i.e., extr yers of life) ctully due to rdicl prosttectomy s opposed to other cuses. 19 After seven yers, ptients undergoing rdicl prosttectomy hd probbility of deth 0.01 higher thn those receiving expectnt mngement. However, clcultion of 95-percent confidence intervl round this figure indictes tht the dt re ctully consistent with probbility of deth with rdicl prosttectomy s much s 0.07 lower thn tht for expectnt mngement s well s probbility s much s 0.09 higher thn tht for expectnt mngement. 20 The reserchers nlyzed Medicre clims dt nd performed survey bsed on ntionl probbility smple of 1,070 men who hd rdicl prosttectomies under Medicre between 1988 nd 1990; they oversmpled Msschusetts for subexperiment to determine whether mode of interview (personl, mil, or phone) gve different results. The method of interview did not ffect ny of the dt presented in this pper (127).

10 42 COSTS AND EFFECTIVENESS OF PROSTATE CANCER SCREENING IN ELDERLY MEN TABLE 4-3: ADVERSE OUTCOMES OF RADICAL PROSTATECTOMY AMONG MEDICARE BENEFICIARIES Condition Percent of men reporting Attributble 30-dy post-opertive mortlity 0.6% Crdiopulmonry complictions b Incontinence Wore pds or other devices for incontinence c 31.0 Dripped more thn few drops dily 23.0 Underwent surgicl tretment for incontinence 6.0 Hd ctheter 2.0 Impotence Hd bility to hve erections prior to surgery 90.0 No full or prtil erections since surgery 61.0 Hd erections firm enough for intercourse in previous month 11.0 Underwent medicl/surgicl tretment for stricture, 2-4 yers fter surgery 20.0 Totl 30-dy post-opertive mortlity (1%) minus probbility of deth for other cuses. b Congestive hert filure, myocrdil infection, pulmonry embolism, or respirtory filure. c Over 80% of these men reported dripping every dy, indicting these pds nd devices were not just used prophylcticlly. SOURCE: Office of Technology Assessment Dt from F.J. Fowler, M.S. Brry, A. Romn, et l. Ptient-Reported Complictions nd Follow-up Tretment After Rdicl Prosttectomy, The Ntionl Medicre Experience: (Updted June 1993), Urology 42(6): , there is evidence of recurrence, spred, or indictions tht the ptients re t high risk of such problems. For men who hve hd rdition tretment, the clinicin cn consider slvge rdicl prosttectomy with evidence of locl progression (297, 370), but the results re usully disppointing (67). After initil tretment by rdicl prosttectomy, clinicins often consider djuvnt rdition or ndrogen deprivtion therpy for men t higher risk of hrboring residul cncer, prticulrly those with positive surgicl mrgins or PSA test vlues tht do not fll to femle levels, lthough it is controversil whether these djuvnt tretments improve survivl (77, 373). Furthermore, clinicins follow ptients closely for evidence of recurrent disese with periodic DRE nd PSA testing (35, 289). Men with evidence of recurrence re often considered for dditionl tretment with rdition. As is the cse for men treted expectntly, ndrogen deprivtion therpy my be instituted for men with loclly symptomtic cncer recurrence, for men who develop distnt metstses, or for some men without symptoms but progressive bnormlity on DRE or rising PSA. In the survey of Medicre-ge men who underwent rdicl prosttectomy between 1988 nd 1990 discussed bove, 5 percent reported followup rdition therpy within the first yer (probbly for residul disese), nd nother 13 percent underwent rdition therpy between the beginning of the second nd the end of the fourth yer of followup (probbly for evidence of recurrence). Ten percent of men hd hormonl therpy prescribed in the four yers following their opertion, nd 15 percent hd n orchiectomy.