P (RCC) was first done in the late 1930s and reported in

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1 Pulmonry Resection of Metsttic Renl Cell Crcinom Robert J. Cerfolio, MD, Mrk S. Allen, MD, Clude Deschmps, MD, Richrd C. Dly, MD, Steven L. Wllrichs, BS, Victor F. Trstek, MD, nd Peter C. Pirolero, MD Sections of Generl Thorcic Surgery nd Biosttistics, Myo Clinic nd Myo Foundtion, Rochester, Minnesot Between 965 nd 989, 96 consecutive ptients (64 men nd 32 women) underwent complete pulmonry resection for metsttic renl cell crcinom. Medin ge ws 63 yers (rnge, 33 to 82 yers). Medin time between nephrectomy nd pulmonry resection ws 3.4 yers (rnge, 0 to 8.4 yers). Forty-eight ptients hd solitry metstsis, 6 hd two, 8 hd three, nd 4 hd more thn three. Wedge excision ws performed in 62 ptients, segmentectomy in 3, lobectomy in 25, bilobectomy in 3, nd pneumonectomy in 3. Fourteen ptients hd repet thorcotomy for recurrent metstsis; 34 other ptients lso hd complete resection of limited extrpulmonry disese. There were no opertive deths. Medin follow-up ws 3 yers (rnge, 70 dys to 9.0 yers). Overll 5-yer survivl ws 35.9%. Ptients with solitry metstsis hd 5-yer survivl of 45.6% compred with 27.0% for ptients with multiple metstses (p < 0.05). Ptients with tumor-free intervl greter thn the medin of 3.4 yers hd better survivl (p = 0.05) thn those with tumor-free intervl less thn or equl to 3.4 yers. Fiveyer survivl for ptients who underwent repet thorcotomy or hd complete resection of extrpulmonry disese did not differ from overll survivl. We conclude tht resection of renl lung metstsis is sfe nd effective, tht ptients with solitry metstsis hve better survivl thn those with multiple metstses, tht resectble extrpulmonry disese does not necessrily contrindicte pulmonry resection, nd tht repet thorcotomy is wrrnted in selected ptients with recurrent lung metstses. (Ann Thorc Surg 994;57:33944) ulmonry resection of metsttic renl cell crcinom P (RCC) ws first done in the lte 930s nd reported in 938 by Brney nd Churchill [l]. They performed this procedure on 55-yer-old womn who subsequently survived for 23 yers. Since then, mny ptients hve undergone similr procedures. Yet, pulmonry resection remins controversil, nd the fctors tht determine long-term survivl re not completely understood. Most series re limited by smll numbers of ptients. Few reports hve ddressed the role of repet thorcotomy for recurrent cncer nd the role of pulmonry resection in the presence of limited extrpulmonry disese. The purpose of this review ws to nlyze our experience with pulmonry resection for metsttic RCC nd to identify those fctors ssocited with prolonged survivl. Mteril nd Methods Between Jnury, 965, nd December 3, 989, 47 consecutive ptients underwent thorcotomy for metsttic RCC t our institution. Ninety-six ptients underwent complete resection. Resection ws considered complete if ll known pulmonry cncer ws removed t thorcotomy. The remining 5 ptients who hd pulmo- Presented t the Twenty-ninth Annul Meeting of The Society of Thorcic Surgeons, Sn Antonio, TX, Jn 25-27, 993. Address reprint requests to Dr Allen, Myo Clinic, 0 First St SW, Rochester, MN nry biopsy only or incomplete resections were excluded from further nlysis. Only ptients tht hd cler cell renl crcinom were included. Ptients who hd complete resections of ll known extrpulmonry disese were lso included. The records of ll 96 ptients were reviewed for ge nd sex, dimeter, grde, TNM clssifiction, nd mngement of the primry RCC; tumor-free intervl; loction, dimeter, grde, nd number of pulmonry metstses; number nd extent of pulmonry resection, complictions, nd long-term survivl. All RCCs were stged postsurgiclly by the TNM clssifiction system of the Americn Joint Committee for Cncer Stging nd End Results Reporting (Tble ) [2]. Opertive mortlity included ptients who died within 30 dys fter thorcotomy or those who died lter but during the sme hospitliztion. Survivl ws estimted by the Kpln-Meier method using the dte of pulmonry resection s the strting point [3]. The influence of vribles on survivl ws nlyzed using the log-rnk test for discrete vribles [4] nd the proportionl hzrds model of Cox for continuous vribles [5]. Vlues of p less thn 0.05 were considered sttisticlly significnt. Clinicl Findings The medin ge of the 96 ptients (64 men nd 32 women) ws 63 yers (rnge, 3 to 82 yers) t the time of their first thorcotomy. The RCC ws locted in the right kidney in 40 ptients nd in the left in 56. A rdicl nephrectomy ws performed in 93 ptients, rdicl nephrectomy plus by The Society of Thorcic Surgeons /94/$7.00

2 340 CERFOLIO ET AL Ann Thorc Surg 994;5733% Tble. RCC Stging System-TNM Clssifiction T T2 T3 T3b T3c T4 NO N N2 N3 MO M Stge I Stge I Stge Stge IV Clssifiction Description Any size, no renl distortion Renl distortion Invdes perinephric tissue (ft), through cpsule Invdes renl vein Invdes renl vein nd infrdiphrgmtic inferior ven cv Invdes djcent structures No nodes involved with tumor Single node involved Multiple regionl nodes involved Fixed nodes No metsttic nodules Metsttic lesions T NO MO, T2 NO MO T3 NO MO T3b NO MO, T3c NO MO, ny T with N-3 T4 NO MO, ny T or N with M tumor thrombus excision in 2 ptients, nd heminephrectomy in ptient. The tumor ws grde in 6 ptients, grde 2 in 57, grde 3 in 2, nd grde 4 in 2 ptients. Medin tumor dimeter ws 8.0 cm (rnge, 2.5 to 8.0 cm). The neoplsm ws postsurgiclly clssified s stge I in 36 ptients, stge I in 34, stge I in 2, nd stge IV in 5 ptients. Ten ptients hd T renl tumors, 27 hd T2, 35 hd T3, hd T3b, 3 hd T3c, nd ptient hd T4. Lymph nodes were clssified s NO in 94 ptients nd either N or N2 in ptient ech. Distnt metstses were bsent in 92 ptients (MO); the remining 4 ptients ll hd pulmonry metstsis (Ml). Sixty-eight ptients hd no djuvnt tretment fter pulmonry resection; 3 hd rdition, 7 hd chemotherpy, 5 hd immunotherpy, nd 3 hd vrious combintions. Pulmonry metstses were symptomtic in 85 ptients (88.5%). Symptoms in the remining ll ptients included hemoptysis in 6, cough in 3, pin in, nd cough nd pin in. Computed tomogrphy (CT) ws vilble during the ltter time period of this study nd ws performed in 72 ptients. CT predicted the correct number of metsttic nodules in 5 of the 72 utients (70.8%). In 2 ptients (29.2%), 79 dditionl metsttic nodules were found t thorcotomy (Tble 2). All ptients were evluted preopertively for locl recurrence of their RCC. Abdominl CT ws the proce- Tble 2. Accurcy of Computed Tomogrphy in Finding Pulmonry Nodules Number of Metstses Number of CT Accurcy Predicted by CT Ptients ("/.I Multiple 4 00 CT = computed tomogrphy. dure most commonly performed. Bone nd brin or liver scns were performed if clinicl or lbortory findings suggested metstses in these res. All pulmonry resections were performed t our institution. Pulmonry resection followed nephrectomy in 92 ptients. No ptient hd spontneous regression of their pulmonry metstsis fter nephrectomy. Four ptients hd concomitnt pulmonry resection nd nephrectomy. The medin intervl between nephrectomy nd the dignosis of pulmonry metstsis ws 3.4 yers (rnge, 0 to 8.4 yers). Lterl thorcotomy ws performed in 92 ptients nd medin sternotomy in 4 ptients. No ptient underwent stged or simultneous bilterl thorcotomies. Fifty-three ptients hd wedge excisions; 23 of these were multiple. A lobectomy ws performed in 25 ptients, pneumonectomy in 3, segmentectomy in 3, nd bilobectomy in 3. Another 6 ptients hd wedge excision combined with lobectomy nd 3 ptients hd wedge excision combined with segmentectomy. At opertion, pulmonry metstses were unilterl in 92 ptients (52 right nd 40 left) nd bilterl in 4 ptients. Two hundred thirty-nine metstses were resected in these 96 ptients (Fig ). Forty-eight ptients (50%) hd solitry pulmonry metstsis, 6 hd two, 8 hd three, 4 hd four, 3 hd five, 2 hd six, 2 hd seven, hd eight, hd 7, nd hd 23. The medin dimeter of the pulmonry metstses ws 2.0 cm (rnge, 0.5 to 7.0 cm). Six ptients lso hd RCC in intrpulmonry lymph nodes (Nl), 4 ptients by direct extension nd 2 by metstsis. Five other ptients hd metstses to N2 lymph nodes nd ptient to N3 lymph node. The metsttic pulmonry lesions were Broders' grde in 7 ptients, grde 2 in 55, grde 3 in 28, nd grde 4 in 6. Eleven ptients hd second thorcotomy, nd 3 of these ptients hd third thorcotomy. Eight ptients underwent reopertion on the ipsilterl thorx. The medin intervl between the first nd second thorcotomy ws 4 months (rnge, month to 0 yers); the intervl between the second nd third thorcotomy ws 3 months, 57 months, nd 2 yers. Eleven reopertions were wedge excision only; the remining three were segmentectomy, lobectomy, nd pneumonectomy in ptient ech. Thirty-four ptients hd resection of limited extrpul- Fig I. Locution of the 239 renl cell metstses.

3 Ann Thorc Surg 994; CERFOLIO ET AL 34 monry disese. All ptients hd solitry metstsis tht were locted in the bone in, brin in 0, bdominl cvity in 8, sclp in 2, nd thyroid, pncres, nd neck in ptient ech. Four ptients hd extrpulmonry disese resected from 6 months to 3 yers before pulmonry resection; the remining 30 ptients hd their extrpulmonry disese resected up to 2 months fter thorcotomy. Seven of the ltter 30 ptients hd extrpulmonry metstsis discovered t the sme time s pulmonry metstsis. Results Complictions occurred in 9 ptients nd included tril fibrilltion in 6 (6.3%), pneumoni in 2 (2.%), nd prolonged ir lek (4 dys) in ptient (%). There were no opertive deths. Follow-up ws complete in ll ptients nd rnged from 70 dys to 9 yers (medin, 3.0 yers). Metsttic RCC recurred in 52 ptients (54.2%)(Tble 3). Recurrence ws to multiple orgn systems in 7 ptients nd involved the lungs in 6 ptients. In 2 other ptients, recurrence ws limited to the lungs. Altogether, recurrence fter pulmonry resection involved the lungs in 8 ptients (34.6%). Twenty-two ptients re currently live, none with evidence of cncer. Seventy-four ptients re ded, 52 from recurrent RCC. Overll estimted 5-yer survivl ws 35.7% (Fig 2) nd did not differ for the three decdes of this study. Survivl ws not influenced by ge, sex, RCC TNM clssifiction, pulmonry signs nd symptoms, loction or dimeter of the pulmonry metstses, or extent of pulmonry resection. Only the number of pulmonry metstses nd tumor-free intervl influenced survivl. Five-yer survivl for ptients with solitry metstsis ws 45.6% compred with 27.0% (Fig 3) for ptients with multiple metstses (p < 0.05). Similrly, 5-yer survivl for ptients with tumor-free intervl more thn 3.4 yers ws 45.4% compred with 26.0% (Fig 4) for ptients less thn or equl to 3.4 yers (p < 0.0). The 62 ptients who underwent wedge excision only hd 5-yer survivl of 3.7% (medin, 3.7 yers) s compred with 42.8% (medin, 4.2 yers) for the 34 ptients who hd either pneu- Tble 3. Loction of Recurrence Loction Bone Lung Brin AbdomenAiver Crcinomtosis Lung nd bone Lung nd brin Lung nd ribs Brin nd bones Adrenl Pncres Thyroid Extremity No. of Ptients Fig 2. Overll probbility of survivl (deth from ny cuse) of the 96 ptients undergoing curtive pulmon y resection of cler cell renl crcinom metsttic to the lung. Zero time on the bsciss represents the dte of pulmonry resection. monectomy, lobectomy, or segmentectomy (p = not significnt). The 5 ptients who hd pulmonry biopsy only or incomplete resection hd 5-yer survivl of only 6.7% (medin, 5 months). Survivl of the 34 ptients who hd extrpulmonry disese resected did not differ significntly from the 62 ptients without extrpulmonry disese (Fig 5). The 30 ptients who hd extrpulmonry disese resected fter thorcotomy hd 5-yer survivl of 37.5%; however, none of the 4 ptients tht hd their extrpulmonry disese resected before thorcotomy survived longer thn 3 yers 7 months. Five-yer survivl for the ptients from the dte of their second thorcotomy ws 30.8% nd did not differ significntly from the 33.3% survivl observed for the 85 ptients who hd only one thorcotomy (Fig 6). Two of the 3 ptients who underwent third thorcotomy died 6 nd 8 yers fter their lst resection of other cuses. The 00 ru.- > $ 60 rn c K Q) 40 $2 (I) Solitry - 2 TWO P c \ Fig 3. Probbility of survivl (deth from ny cuse) of the 48 ptients undergoing curtive pulmon y resection of solit y renl cell crcinom metsttic to the lung s compred with 48 ptients with multiple pulmonry metstses (p < 0.05). Zero time on the bsciss represents the dte of pulmonry resection.

4 342 CERFOLIO ET AL Ann Thorc Surg 994;57: > 5 60 fn Y C 8 40 t 0 \ > 3.4 yrs \ \ - I 3.4 yrs ** P c 0.0 \ ', I I I I I I l l I II Fig 4. Probbility of survivl (deth from ny cuse) of the 48 ptients undergoing curtive pulmon y resection of renl cell crcinom metsttic to the lung with tumor-free intervl of less thn or equl to 3.4 yers s compred with 48 ptients with tumor-free intervl of greter thn 3.4 yers (p < 0.0). Zero time on the bsciss represents the dte of pulmonry resection. remining ptient is live without recurrence 3 yers fter the third thorcotomy. Comment Ech yer in the United Sttes RCC develops in pproximtely 25,000 ptients, nd this represents pproximtely 3% of ll dult mlignncies [6]. Twenty-five to 30% of these ptients hve metstses t the time the RCC is dignosed, nd 30% to 50% will develop pulmonry metstses lter [7, 8. The 5-yer survivl of ptients with unresected metsttic RCC is only 2.7% [9]. Chemotherpy, rdition therpy, nd immunotherpy hve not been proven to be effective tretment for metsttic disese [lo-5, nd surgery remins the only effective tretment for ptients with limited metsttic RCC. Evlution of ptients with history of RCC who present with pulmonry nodule should include history nd physicl exmintion. RCC cn metstsize to unusul loctions such s the pncres, thyroid, gllbldder, iris, nd epididymis [6]; thus, the preopertive evlution should be thorough. Old chest roentgenogrms should be exmined to determine if the nodule ws present in the pst. Chest CT should be obtined to serch for dditionl pulmonry nodules or medistinl denopthy. The CT should lso include the liver, drenls, nd bed of the resected kidney to exclude bdominl recurrence. If no evidence of bdominl recurrence is found nd the ptient is n cceptble surgicl risk, the pulmonry nodule should be resected. We fvor lterl thorcotomy for unilterl disese nd medin sternotomy for bilterl disese. At opertion, the lung should be plpted crefully nd ll nodules locted before beginning resection. Enlrged lymph nodes should be resected. Although thorcoscopy hs been used recently to resect metsttic nodules [7], we believe tht this is n indequte curtive tretment. Becuse thorcoscopy does not llow dequte plption of the remining lung, nodules not visulized on CT will remin undetected. Our dt indicte tht pproximtely onethird of the ptients hd dditionl nodules resected t thorcotomy tht were not detected by CT. We hve reported similr findings for colorectl pulmonry metstses [ 8. Thus, thorcoscopy lone would probbly result in lower 5-yer survivl. Consequently, thorcoscopic resection of metsttic nodules should be limited to dignosis only. Resection cn usully be ccomplished by wedge excision. Occsionlly, it is necessry to perform segmentectomy, lobectomy, or even pneumonectomy. In our series, ptients who hd more extensive resection tended to hve better survivl, lthough not sttisticlly significnt. In ptients with bilterl metstses, complete resection cn often be ccomplished by medin sternot $60 fn CI c 8 40 t v) c C 8 40 t ---- Single - Multiple Fig 5. Probbility of survivl (deth from ny cuse) of the 62 ptients undergoing curtive pulmon y resection of renl cell crcinom metsttic to the lung without extrpulmon y disese s compred with 34 ptients with limited extrpulmony disese (p = not significnt). Zero time on the bsciss represents the dte of pulmonry resection. n Fig 6. Probbility of survivl (deth from ny cuse) of 82 ptients undergoing single thorcotomy for renl cell crcinom metsttic to the lung s compred with 4 ptients who underwent multiple thorcotomies for recurrent renl cell crcinom to the lungs. Zero time on the bsciss represents the dte of the lst thorcotomy.

5 Ann Thorc Surg 994: CERFOLIO ET AL 343 omy. However, if the lesions re locted posteriorly in the left lower lobe, bilterl stged thorcotomies my be preferble lterntive. Differentiting RCC pulmonry metstsis from primry lung cncer cn be difficult t times. Lymph node involvement from hemtogenous metstsis to the lungs is unusul. In the present series, only 2 ptients hd lymph node metstses. Consequently, if extensive lymph node metstses re present, the pulmonry nodule my be primry lung cncer rther thn n RCC metstsis. If the lesion cnnot be differentited from primry lung cncer t the time of opertion, the lesion should be mnged s lung cncer with lobectomy nd medistinl node dissection. In our series, ptients with solitry pulmonry nodule hd 5-yer survivl of 45.6%. Although the survivl of ptients with multiple pulmonry metstses ws significntly less (27.0%), it ws better thn the nturl history of unresected metsttic disese. Thus, pulmonry resection is wrrnted for selected ptients with multiple pulmonry metsttic nodules, including ptients with bilterl nodules. However, when CT revels numerous nodules, resection is less likely to be beneficil. An erlier study from our institution demonstrted 5-yer survivl of 27% [9]. Our present survivl of 35.7% is slightly better becuse ptients who hd incomplete resection were excluded. Our previous study demonstrted tht both disese-free intervl nd the dimeter of the lrgest nodule resected ffected survivl. In the present study, the dimeter of the lrgest nodule resected ws not significnt predictor of survivl. The erlier study my hve reched different conclusion becuse of the smller number of ptients involved. Other uthors hve reported vrying dt. Tobisu nd collegues [] in 990, nd Pogrebnik nd co-workers [2] in 99, demonstrted no difference in survivl mong ptients with single versus multiple pulmonry metstses. However, Ktzenstein nd collegues [22] in 978, nd our present study demonstrted tht ptients with multiple metstses hd lower 5-yer survivl. These differences my be ttributble to the lrger number of ptients in our series. Usul criteri for resectbility in ptients with pulmonry metstsis is the bsence of extrpulmonry disese. However, our 5-yer survivl of ptients who hd limited extrpulmonry disese resected ws similr to tht observed for ptients without extrpulmonry metstsis. We hve reported similr findings for colorectl pulmonry metstses [8]. Although ptients with limited extrpulmonry disese represent selected popultion, combined pulmonry nd extrpulmonry resection ppers to offer resonble chnce for cure, nd we continue to recommend resection in these ptients. Close surveillnce is necessry to detect recurrent disese. We recommend binnul chest roentgenogrm nd chest CT. Follow-up must be lifelong becuse recurrent pulmonry metstses developed s long s 0 yers fter the first thorcotomy nd 2 yers fter the second. Fourteen ptients hd repet thorcotomy. Their 5-yer survivl ws similr to tht observed for our ptients with single thorcotomy. Importntly, ptients undergoing repet thorcotomy hd no increse in either morbidity or mortlity. Moreover, ll of our ptients who underwent third thorcotomy were live t lest 5 yers fter the first resection. Hence, we continue to recommend repet thorcotomies for recurrent metsttic RCC in selected ptients. We conclude tht pulmonry resection of metsttic renl cell crcinom is sfe nd effective, tht ptients with solitry metstsis hve better survivl thn those with multiple metstses, tht resectble extrpulmonry disese does not necessrily contrindicte pulmonry resection, nd tht repet thorcotomy is wrrnted in selected ptients with recurrent lung metstses. References. Brney JD, Churchill EJ. Adenocrcinom of the kidney with metstsis to the lung. J Urol 939;42: Behrs OH, Myers MH (eds). Americn Joint Commission on Cncer: Mnul for stging of cncer, 2nd ed. Phildelphi: Lippincott, 983: Kpln EL, Meier P. Non-prmetric estimtion from incomplete observtions. J Am Stt Assoc 958;53:457-&. 4. Pet0 R, Pet0 J. Asymptoticlly efficient rnk nd invrint procedures. J R Sttist SOC, Series A 972;35: Cox DR. Regression models nd life-tble (with discussion). J R Sttist SOC, Series B 972;34: Boring CC, Squires TS, Tong T. Cncer sttistics, 99. Cncer 99;4:% Dekernion JB, Rmming KP. The nturl history of metsttic renl cell crcinom: computer nlysis. J Urol 978; : Ptel NP, Lvenwook RW. Renl cell cncer: history nd results of tretment. J Urol 978;9: Riches E. The nturl history of renl tumors. In: Tumors of the kidney nd ureter. Edinburgh: Churchill Livingstone, 984: Poster DS, Bruno S, Pent JS. Current sttus of chemotherpy, hormonl therpy, nd immunotherpy in the tret- ment of renl cell crcinom. Am J Clin Oncol 982;5:5?-60.. Luderer RC, Opipri ML, Perrott AL. Tretment of metsttic renl cell crcinom: review of experience nd world literture. J Am Oncol Assoc 978;7759M Rosenberg SA, Lotze MT, Moul LM. A progress report on the tretment of 57 ptients with dvnced cncer using lymphokine ctivted killer cells nd interleukin-2. N Engl J Med 987;36: Thompson JA, Lee DJ, Cox W. Recombinnt interleukin-2 toxicity, phrmcokinetics, nd immunotherpy effects in phse I tril. Cncer Res 987;47: Bukowski RM, Osgood 8, Sergi J. Phse INIB tril of interleukin-2 nd interferon-2. Results in metsttic renl cell cncer. J Urol 988;39:283A. 5. Rosenberg SA, Lotze MT, Yng JC. Experience with use of high dose interleukin-2 in tretment of 652 cncer ptients. Ann Surg 989;:47p Tbr WS, Mchio AM, Aftimus GP. Metsttic renl cell crcinom-renl tumors. Proceedings of First Interntionl Symposium on Kidney Tumors. New York Liss, Dowling RD, Ferson PF, Lndreneu RJ. Thorcoscopic resection of pulmonry metstses. Chest 992;02:45&4. 8. McAfee MK, Allen MS, Trstek VF, et l. Colorectl lung metstses: results of surgicl excision. Ann Thorc Surg 992;53:78M. 9. Jett JR, Hollinger CG, Zinsmiester AR, Pirolero PC. Pulmonry resection of metsttic renl cell crcinom. Chest 983;84: Tobisu K, Kkigie T. Surgicl tretment of metsttic renl cell crcinom. Jpn J Clin Oncol 990;:263-7.

6 344 CERFOLIO ET AL Ann Thorc Surg 994; Pogrebnik HW, Hs G, Linehn WM, Rosenberg SA, Pss HI. Renl cell crcinom: resection of solitry nd multiple metstses. Ann Thorc Surg 992;54: Ktzenstein AL, Purvis R Jr, Gmelich J, Askin F. Pulmonry resection for metsttic renl denocrcinom. Cncer 978; 4 : DISCUSSION DR JACK A. ROTH (Houston, TX): I believe this report represents n importnt contribution. Resection of isolted pulmonry metstses is n ccepted tretment modlity, nd it remins ccepted despite the complete bsence of prospective clinicl trils definitively documenting efficcy. This cceptnce is bsed on the retrospective review of cses tht document long-term survivl in ptients such s the ones tht hve just been presented who do not hve ny other curtive tretments vilble. Survivl t 5 yers for some groups of ptients with isolted pulmonry metstses fter resection is superior to the overll survivl of ptients with primry lung cncer. Nevertheless, mny ptients do not pper to benefit from resection of their metstses, nd it would be extremely helpful to the surgeon to be ble to select in dvnce those ptients for whom resection offered high probbility of fvorble outcome. The report by Dr Cerfolio nd his collegues provides help by identifying some of these prognostic fctors. However, I think severl cvets should be mentioned. The prognostic fctors they identify re not sufficiently precise to be used to exclude ptients from surgery. In their study, ptients with multiple metstses still hd 27% 5-yer survivl, lthough this ws lower thn the group hving solitry metstsis. It my not be pproprite to exclude ptients with dverse prognostic fctors from surgicl resection if there re no other potentilly curtive tretment options nd if the morbidity of the surgery is felt to be low. Ptients with isolted pulmonry metstses re very heterogeneous group. For exmple, it is not possible to extrpolte dt on prognostic fctors from ptients with dult soft tissue srcoms to ptients with other tumor histologies. Prognostic fctors, such s the number of metstses resected nd tumor doubling time, my be predictive for srcom ptients but not for other types of histologies. For osteogenic srcom nd soft tissue srcom the number of metstses resected, three or fewer, ws predictive of improved survivl. Tumor doubling time ws predictive for soft tissue srcoms, but not for osteogenic srcom. For brest nd melnom, these predictive fctors my not lwys pply. I would like to point out the very heterogeneous survivl rtes t 5 yers for these vrious histologies. Our experience t M.D. Anderson with respect to reopertion for srcom ptients does gree with the Myo Clinic experience for reopertion for hypernephrom. Although these groups re not completely comprble, I think this does point out tht n ggressive surgicl pproch to these ptients cn be beneficil. For exmple, here re three groups of ptients hving only one, two, or three resections of dult soft tissue srcoms. The medin survivl is essentilly identicl for ll three groups tht hd resections. I hve severl questions for Dr Cerfolio nd ssocites. Wht criteri did you use to distinguish between metstsis nd secondry primry cncer in ptients with solitry lung lesion? Some of your ptients hd very prolonged disese-free intervl, suggesting second primry lesion. Do you give djuvnt therpy before or fter resection of the metstses, nd if so, wht is the proper timing for surgery? Hypernephrom is quite responsive to some types of biologic therpy such s interleukin-2 or interferon. There were 3 ptients in your series tht hd pneumonectomy. Wht do you feel re the pproprite indictions for pneumonectomy for metsttic hypernephrom, nd wht ws the outcome for these ptients? I congrtulte Dr Cerfolio nd ssocites on their excellent presenttion nd thnk The Society for the privilege of discussing this report. DR BENEDICT D. T. DALY (Boston, MA): We enjoyed this report very much. I noted tht the series ended in 989, which prompts two or three comments nd question. Since 988 we hve operted on number of ptients with metsttic hypernephrom fter interleukin-2 therpy. Ptients with metstses limited to the lung hve in generl fllen into two groups. In the ptients with single nodules tht hve remined stble fter interleukin-2 therpy we hve undertken resection for cure. The other group of ptients re those who hve multiple pulmonry nodules nd no evidence of disese elsewherethese we hve tended to follow. Over the course of time most of the nodules in this group will remin stble, but one or two of the nodules my increse in size. In these ptients we hve resected the enlrging nodule nd ll of the other nodules in the ipsilterl chest. The enlrging nodules hve invribly contined cncer, the stble nodules in mny cses hve been inflmmtory, nd in other cses hve contined cncer. The third observtion we hve mde is tht when operting on these ptients in proximity to interleukin-2 therpy nd by tht I men within the first 4 to 6 months, there cn be enlrged hilr nodes with n intense perivsculr rection secondry to perinodl inflmmtion, mking resection difficult. I would like to sk the uthors if they hve hd ny experience in resecting hypernephrom in ptients fter interleukin-2 therpy nd if so, hve they estblished ny guidelines for mngement. DR CERFOLIO: Thnk you, Drs Roth nd Dily for your comments. To nswer Dr Roths questions first, we gree tht the prognostic fctors tht we identified re not precise, nd they, by themselves, should not preclude pulmonry resection. Deciding if lung neoplsm is primry cncer versus metstsis cn be difficult. In this study pulmonry neoplsm ws considered metstsis if the histologic fetures were similr to the originl primry cncer. Cliniclly, if there is ny equivoclity s to the histologicl nture of pulmonry nodule, the lesion should be treted s primry lung cncer. One of your questions, Dr Roth, ddressed djunctive tretment. We did hve 3 ptients who were treted with interleukin-2, but s Dr Dly mentioned, the dt were preliminry. Most of our ptients received different doses nd different schedules tht re currently being recommended. Therefore, we cn mke no conclusions s to the vlue of preopertive interleukin-2. Doctor Roths lst question ws the criteri for pneumonectomy. In generl, the number of pulmonry metstses did not dictte this procedure; rther the extent of centrl disese ws more importnt. Of course, good pulmonry function ws mndtory. Doctor Dly, I believe I hve lredy nswered your question bout interleukin-2.