Positive surgical margins in nephron-sparing surgery: risk factors and therapeutic consequences

World Journal of Surgical Oncology

Andres Jan Schrader²  Konrad Steinestel¹  Sandra Steffens³  Julie Steinestel² 

[1] Department of Pathology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany;Department of Urology, Münster University Medical Center, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany;Department of Urology, Hannover University Medical School, Carl-Neubergstr. 1, 30625 Hannover, Germany

关键词: Survival review;    Prognosis;    R1;    Therapeutic relevance;    Positive surgical margins;    Renal cell carcinoma;   

Others  :  1148381
DOI  :  10.1186/1477-7819-12-252

 received in 2014-03-18, accepted in 2014-07-20,  发布年份 2014

【 摘 要 】

The increased use of nephron-sparing surgery to treat localized renal cell carcinoma (RCC) lends weight to the question of the value of microscopically positive surgical margins (PSM) in cases with a tumor bed macroscopically free of residual tumor. The aim of this article is to highlight the data available on risk factors for PSM, their clinical relevance, and possible therapeutic consequences. For this purpose, publications on the incidence and relevance of PSM after partial nephrectomy from the last 15 years were examined and evaluated. We summarize that PSM are generally rare, regardless of the surgical procedure, and are seen more often in connection with an imperative indication for nephron-sparing surgery as well as a central tumor location. Most studies describe that PSM lead to a moderate increase in the rate of local relapses, but no study has thus far been able to demonstrate an association with shorter tumor-specific overall survival. Intraoperative frozen section analysis had no positive influence on the risk of definite PSM in most trials. Therefore, we conclude that PSM should definitely be avoided. However, in cases with a macroscopically tumor-free intraoperative resection bed, they should lead to close surveillance of the affected kidney and not to immediate (re)intervention.

【 授权许可】

   
2014 Steinestel et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF, Sinescu IC: EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010, 58:398-406.
• [2]Campbell SC, Novick AC, Belldegrun A, Blute ML, Chow GK, Derweesh IH, Faraday MM, Kaouk JH, Leveillee RJ, Matin SF, Russo P, Uzzo RG: Guideline for management of the clinical T1 renal mass. J Urol 2009, 182:1271-1279.
• [3]Minervini A, Serni S, Tuccio A, Siena G, Vittori G, Masieri L, Giancane S, Lanciotti M, Khorrami S, Lapini A, Carini M: Simple enucleation versus radical nephrectomy in the treatment of pT1a and pT1b renal cell carcinoma. Ann Surg Oncol 2012, 19:694-700.
• [4]Coffin G, Hupertan V, Taksin L, Vaessen C, Chartier-Kastler E, Bitker MO, Roupret M: Impact of elective versus imperative indications on oncologic outcomes after open nephron-sparing surgery for the treatment of sporadic renal cell carcinomas. Ann Surg Oncol 2011, 18:1151-1157.
• [5]Peycelon M, Hupertan V, Comperat E, Renard-Penna R, Vaessen C, Conort P, Bitker MO, Chartier-Kastler E, Richard F, Roupret M: Long-term outcomes after nephron sparing surgery for renal cell carcinoma larger than 4 cm. J Urol 2009, 181:35-41.
• [6]Hansen J, Sun M, Bianchi M, Rink M, Tian Z, Hanna N, Meskawi M, Schmitges J, Shariat SF, Chun FK, Perrotte P, Graefen M, Karakiewicz PI: Assessment of cancer control outcomes in patients with high-risk renal cell carcinoma treated with partial nephrectomy. Urology 2012, 80:347-353.
• [7]Becker F, Roos FC, Janssen M, Brenner W, Hampel C, Siemer S, Thuroff JW, Stockle M: Short-term functional and oncologic outcomes of nephron-sparing surgery for renal tumours >/=7 cm. Eur Urol 2011, 59:931-937.
• [8]Hegele A, Skrobek L, Schrader AJ: Update Urooncology: news with clinical relevance from major scientific meetings 2013. Aktuelle Urol 2014, 45:21-32.
• [9]Huang WC, Levey AS, Serio AM, Snyder M, Vickers AJ, Raj GV, Scardino PT, Russo P: Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol 2006, 7:735-740.
• [10]Klarenbach S, Moore RB, Chapman DW, Dong J, Braam B: Adverse renal outcomes in subjects undergoing nephrectomy for renal tumors: a population-based analysis. Eur Urol 2011, 59:333-339.
• [11]Scosyrev E, Messing EM, Sylvester R, Campbell S, Van Poppel H: Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol 2014, 65:372-377.
• [12]Huang WC, Elkin EB, Levey AS, Jang TL, Russo P: Partial nephrectomy versus radical nephrectomy in patients with small renal tumors–is there a difference in mortality and cardiovascular outcomes? J Urol 2009, 181:55-61.
• [13]Thompson RH, Boorjian SA, Lohse CM, Leibovich BC, Kwon ED, Cheville JC, Blute ML: Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol 2008, 179:468-471.
• [14]Weight CJ, Lieser G, Larson BT, Gao T, Lane BR, Campbell SC, Gill IS, Novick AC, Fergany AF: Partial nephrectomy is associated with improved overall survival compared to radical nephrectomy in patients with unanticipated benign renal tumours. Eur Urol 2010, 58:293-298.
• [15]MacLennan S, Imamura M, Lapitan MC, Omar MI, Lam TB, Hilvano-Cabungcal AM, Royle P, Stewart F, MacLennan G, MacLennan SJ, Canfield SE, McClinton S, Griffiths TR, Ljungberg B, N'Dow J, Ucan Systematic Review Reference Group, E. A. U. Renal Cancer Guideline Panel: Systematic review of oncological outcomes following surgical management of localised renal cancer. Eur Urol 2012, 61:972-993.
• [16]Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, Colombel M, Klotz L, Skinner E, Keane T, Marreaud S, Collette S, Sylvester R: A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011, 59:543-552.
• [17]Minervini A, Di Cristofano C, Lapini A, Marchi M, Lanzi F, Giubilei G, Tosi N, Tuccio A, Mancini M, Della Rocca C, Serni S, Bevilacqua G, Carini M: Histopathologic analysis of peritumoral pseudocapsule and surgical margin status after tumor enucleation for renal cell carcinoma. Eur Urol 2009, 55:1410-1418.
• [18]Minervini A, Serni S, Tuccio A, Raspollini MR, Di Cristofano C, Siena G, Vittori G, Saleh O, Lapini A, Carini M: Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single-centre study. BJU Int 2011, 107:1394-1399.
• [19]Carini M, Minervini A, Masieri L, Lapini A, Serni S: Simple enucleation for the treatment of PT1a renal cell carcinoma: our 20-year experience. Eur Urol 2006, 50:1263-1268.
• [20]Steffens S, Junker K, Roos FC, Janssen M, Becker F, Henn D, Wegener G, Siemer S, Hofmann R, Schrader M, Stockle M, Thuroff JW, Hartmann A, Kuczyk MA, Schrader AJ, German Renal Tumor Network: Small renal cell carcinomas - How dangerous are they really? Results of a large multicenter study. Eur J Cancer 2014, 4:739-745.
• [21]Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, Marechal JM, Klotz L, Skinner E, Keane T, Claessens I, Sylvester R: A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2007, 51:1606-1615.
• [22]Schnoeller TJ, De Petriconi R, Hefty R, Jentzmik F, Waalkes S, Zengerling F, Schrader M, Schrader AJ: Partial nephrectomy using porcine small intestinal submucosa. World J Surg Oncol 2011, 9:1-5.
• [23]Sutherland SE, Resnick MI, Maclennan GT, Goldman HB: Does the size of the surgical margin in partial nephrectomy for renal cell cancer really matter? J Urol 2002, 167:61-64.
• [24]Castilla EA, Liou LS, Abrahams NA, Fergany A, Rybicki LA, Myles J, Novick AC: Prognostic importance of resection margin width after nephron-sparing surgery for renal cell carcinoma. Urology 2002, 60:993-997.
• [25]Marszalek M, Carini M, Chlosta P, Jeschke K, Kirkali Z, Knuchel R, Madersbacher S, Patard JJ, Van Poppel H: Positive surgical margins after nephron-sparing surgery. Eur Urol 2012, 61:757-763.
• [26]Borghesi M, Brunocilla E, Schiavina R, Martorana G: Positive surgical margins after nephron-sparing surgery for renal cell carcinoma: incidence, clinical impact, and management. Clin Genitourin Cancer 2013, 11:5-9.
• [27]Masson-Lecomte A, Yates DR, Bensalah K, Vaessen C, de la Taille A, Roumiguie M, Doumerc N, Bruyere F, Soustelle L, Droupy S, Roupret M: Robot-assisted laparoscopic nephron sparing surgery for tumors over 4 cm: operative results and preliminary oncologic outcomes from a multicentre French study. Eur J Surg Oncol 2013, 39:799-803.
• [28]Patard JJ, Pantuck AJ, Crepel M, Lam JS, Bellec L, Albouy B, Lopes D, Bernhard JC, Guille F, Lacroix B, De La Taille A, Salomon L, Pfister C, Soulie M, Tostain J, Ferriere JM, Abbou CC, Colombel M, Belldegrun AS: Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication. Eur Urol 2007, 52:148-154.
• [29]Kwon EO, Carver BS, Snyder ME, Russo P: Impact of positive surgical margins in patients undergoing partial nephrectomy for renal cortical tumours. BJU Int 2007, 99:286-289.
• [30]Zigeuner R, Quehenberger F, Pummer K, Petritsch P, Hubmer G: Long-term results of nephron-sparing surgery for renal cell carcinoma in 114 patients: risk factors for progressive disease. BJU Int 2003, 92:567-571.
• [31]Lau WK, Blute ML, Weaver AL, Torres VE, Zincke H: Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clinic Proceedings 2000, 75:1236-1242.
• [32]Gill IS, Kavoussi LR, Lane BR, Blute ML, Babineau D, Colombo JR Jr, Frank I, Permpongkosol S, Weight CJ, Kaouk JH, Kattan MW, Novick AC: Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol 2007, 178:41-46.
• [33]Marszalek M, Meixl H, Polajnar M, Rauchenwald M, Jeschke K, Madersbacher S: Laparoscopic and open partial nephrectomy: a matched-pair comparison of 200 patients. Eur Urol 2009, 55:1171-1178.
• [34]Gong EM, Orvieto MA, Zorn KC, Lucioni A, Steinberg GD, Shalhav AL: Comparison of laparoscopic and open partial nephrectomy in clinical T1a renal tumors. J Endourol 2008, 22:953-957.
• [35]Bernhard JC, Pantuck AJ, Wallerand H, Crepel M, Ferriere JM, Bellec L, Maurice-Tison S, Robert G, Albouy B, Pasticier G, Soulie M, Lopes D, Lacroix B, Bensalah K, Pfister C, Thuret R, Tostain J, De La Taille A, Salomon L, Abbou C, Colombel M, Belldegrun AS, Patard JJ: Predictive factors for ipsilateral recurrence after nephron-sparing surgery in renal cell carcinoma. Eur Urol 2010, 57:1080-1086.
• [36]Duvdevani M, Mor Y, Kastin A, Laufer M, Nadu A, Golomb J, Zilberman D, Nativ O, Ramon J: Renal artery occlusion during nephron-sparing surgery: retrospective review of 301 cases. Urology 2006, 68:960-963.
• [37]Duvdevani M, Laufer M, Kastin A, Mor Y, Nadu A, Hanani J, Nativ O, Ramon J: Is frozen section analysis in nephron sparing surgery necessary? A clinicopathological study of 301 cases. J Urol 2005, 173:385-387.
• [38]Gill IS, Matin SF, Desai MM, Kaouk JH, Steinberg A, Mascha E, Thornton J, Sherief MH, Strzempkowski B, Novick AC: Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol 2003, 170:64-68.
• [39]Lifshitz DA, Shikanov SA, Deklaj T, Katz MH, Zorn KC, Eggener SE, Shalhav AL: Laparoscopic partial nephrectomy: a single-center evolving experience. Urology 2010, 75:282-287.
• [40]Porpiglia F, Fiori C, Terrone C, Bollito E, Fontana D, Scarpa RM: Assessment of surgical margins in renal cell carcinoma after nephron sparing: a comparative study: laparoscopy vs open surgery. J Urol 2005, 173:1098-1101.
• [41]Permpongkosol S, Colombo JR Jr, Gill IS, Kavoussi LR: Positive surgical parenchymal margin after laparoscopic partial nephrectomy for renal cell carcinoma: oncological outcomes. J Urol 2006, 176:2401-2404.
• [42]Link RE, Bhayani SB, Allaf ME, Varkarakis I, Inagaki T, Rogers C, Su LM, Jarrett TW, Kavoussi LR: Exploring the learning curve, pathological outcomes and perioperative morbidity of laparoscopic partial nephrectomy performed for renal mass. J Urol 2005, 173:1690-1694.
• [43]Porpiglia F, Fiori C, Bertolo R, Scarpa RM: Does tumour size really affect the safety of laparoscopic partial nephrectomy? BJU Int 2011, 108:268-273.
• [44]Breda A, Stepanian SV, Liao J, Lam JS, Guazzoni G, Stifelman M, Perry K, Celia A, Breda G, Fornara P, Jackman S, Rosales A, Palou J, Grasso M, Pansadoro V, Disanto V, Porpiglia F, Milani C, Abbou C, Gaston R, Janetschek G, Soomro NA, de la Rosette J, Laguna MP, Schulam PG: Positive margins in laparoscopic partial nephrectomy in 855 cases: a multi-institutional survey from the United States and Europe. J Urol 2007, 178:47-50.
• [45]Frank I, Colombo JR Jr, Rubinstein M, Desai M, Kaouk J, Gill IS: Laparoscopic partial nephrectomy for centrally located renal tumors. J Urol 2006, 175:849-852.
• [46]Venkatesh R, Weld K, Ames CD, Figenshau SR, Sundaram CP, Andriole GL, Clayman RV, Landman J: Laparoscopic partial nephrectomy for renal masses: effect of tumor location. Urology 2006, 67:1169-1174.
• [47]Scoll BJ, Uzzo RG, Chen DY, Boorjian SA, Kutikov A, Manley BJ, Viterbo R: Robot-assisted partial nephrectomy: a large single-institutional experience. Urology 2010, 75:1328-1334.
• [48]Benway BM, Bhayani SB, Rogers CG, Porter JR, Buffi NM, Figenshau RS, Mottrie A: Robot-assisted partial nephrectomy: an international experience. Eur Urol 2010, 57:815-820.
• [49]Benway BM, Bhayani SB, Rogers CG, Dulabon LM, Patel MN, Lipkin M, Wang AJ, Stifelman MD: Robot assisted partial nephrectomy versus laparoscopic partial nephrectomy for renal tumors: a multi-institutional analysis of perioperative outcomes. J Urol 2009, 182:866-872.
• [50]Mellon MJ, Lucas SM, Kum JB, Cheng L, Sundaram C: A comparison of pathologic outcomes of matched robotic and open partial nephrectomies. Int Urol Nephrol 2013, 45:381-385.
• [51]Verze P, Fusco F, Minervini A, Antonelli A, Bianchi G, Bocciardi A, Cosciani Cunico S, Ficarra V, Fiori C, Giancane S, Longo N, Martorana G, Novara G, Porpiglia F, Rocco F, Rovereto B, Schiavina R, Serni S, Simeone C, Volpe A, Carini M: Simple enucleation versus standard partial nephrectomy for clinical T1 renal tumors: Intraoperative, early post-operative and pathological outcomes from a prospective multicenter comparative study (RECORd Project). Eur Urol Suppl 2013, 12:e172.
• [52]Minervini A, Ficarra V, Rocco F, Antonelli A, Bertini R, Carmignani G, Cosciani Cunico S, Fontana D, Longo N, Martorana G, Mirone V, Morgia G, Novara G, Roscigno M, Schiavina R, Serni S, Simeone C, Simonato A, Siracusano S, Volpe A, Zattoni F, Zucchi A, Carini M: Simple enucleation is equivalent to traditional partial nephrectomy for renal cell carcinoma: results of a nonrandomized, retrospective, comparative study. J Urol 2011, 185:1604-1610.
• [53]Saranchuk JW, Touijer AK, Hakimian P, Snyder ME, Russo P: Partial nephrectomy for patients with a solitary kidney: the Memorial Sloan-Kettering experience. BJU Int 2004, 94:1323-1328.
• [54]Lee DJ, Hruby G, Benson MC, McKiernan JM: Renal function and oncologic outcomes in nephron sparing surgery for renal masses in solitary kidneys. World J Urol 2011, 29:343-348.
• [55]Wszolek MF, Kenney PA, Lee Y, Libertino JA: Comparison of hilar clamping and non-hilar clamping partial nephrectomy for tumours involving a solitary kidney. BJU Int 2011, 107:1886-1892.
• [56]Bensalah K, Pantuck AJ, Rioux-Leclercq N, Thuret R, Montorsi F, Karakiewicz PI, Mottet N, Zini L, Bertini R, Salomon L, Villers A, Soulie M, Bellec L, Rischmann P, De la Taille A, Avakian R, Crepel M, Ferriere JM, Bernhard JC, Dujardin T, Pouliot F, Rigaud J, Pfister C, Albouy B, Guy L, Joniau S, van Poppel H, Lebret T, Culty T, Saint F: Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery. Eur Urol 2010, 57(3):466-471.
• [57]Yossepowitch O, Thompson RH, Leibovich BC, Eggener SE, Pettus JA, Kwon ED, Herr HW, Blute ML, Russo P: Positive surgical margins at partial nephrectomy: predictors and oncological outcomes. J Urol 2008, 179:2158-2163.
• [58]Raz O, Mendlovic S, Shilo Y, Leibovici D, Sandbank J, Lindner A, Zisman A: Positive surgical margins with renal cell carcinoma have a limited influence on long-term oncological outcomes of nephron sparing surgery. Urology 2010, 75:277-280.
• [59]Ani I, Finelli A, Alibhai SM, Timilshina N, Fleshner N, Abouassaly R: Prevalence and impact on survival of positive surgical margins in partial nephrectomy for renal cell carcinoma: a population-based study. BJU Int 2013, 111:E300-E305.
• [60]Venigalla S, Wu G, Miyamoto H: The impact of frozen section analysis during partial nephrectomy on surgical margin status and tumor recurrence: a clinicopathologic study of 433 cases. Clin Genitourin Cancer 2013, 11:527-536.
• [61]Timsit MO, Bazin JP, Thiounn N, Fontaine E, Chretien Y, Dufour B, Mejean A: Prospective study of safety margins in partial nephrectomy: intraoperative assessment and contribution of frozen sections [abstract 638]. Eur Urol Suppl 2006, 5:182.
• [62]Palermo SM, Dechet C, Trenti E, Mian C, Lodde M, Comploj E, Mazzoleni G, Hanspeter E, Ambrosini Spaltro A, Mayr R, Pycha A: Cytology as an alternative to frozen section at the time of nephron-sparing surgery to evaluate surgical margin status. Urology 2013, 82:1071-1075.
• [63]Sterious SN, Simhan J, Smaldone MC, Tsai KJ, Canter D, Wameedh E, Li T, Helstrom J, Viterbo R, Chen DY, Greenberg RE, Kutikov A, Al-Saleem T: Is there a benefit to frozen section analysis at the time of partial nephrectomy? Can J Urol 2013, 20:6778-6784.
• [64]Hillyer SP, Yakoubi R, Autorino R, Isac W, Miocinovic R, Laydner H, Khalifeh A, Stein RJ, Haber GP, Kaouk JH: Utility of intraoperative frozen section during robot-assisted partial nephrectomy: a single institution experience. J Endourol 2013, 27:324-327.
• [65]Hagemann IS, Lewis JS Jr: A retrospective comparison of 2 methods of intraoperative margin evaluation during partial nephrectomy. J Urol 2009, 181:500-505.
• [66]Khalifeh A, Kaouk JH, Bhayani S, Rogers C, Stifelman M, Tanagho YS, Kumar R, Gorin MA, Sivarajan G, Samarasekera D, Allaf ME: Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind). J Urol 2013, 190:1674-1679.
• [67]Haferkamp A, Kurosch M, Pritsch M, Hatiboglu G, Macher-Goeppinger S, Pfitzenmaier J, Pahernik S, Wagener N, Hohenfellner M: Prognostic factors influencing long-term survival of patients undergoing nephron-sparing surgery for nonmetastatic renal-cell carcinoma (RCC) with imperative indications. Ann Surg Oncol 2010, 17:544-551.
• [68]Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H: An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the sign score. J Urol 2002, 168:2395-2400.
• [69]Sundaram V, Figenshau RS, Roytman TM, Kibel AS, Grubb RL 3rd, Bullock A, Benway BM, Bhayani SB: Positive margin during partial nephrectomy: does cancer remain in the renal remnant? Urology 2011, 77:1400-1403.
• [70]Ray ER, Turney BW, Singh R, Chandra A, Cranston DW, O'Brien TS: Open partial nephrectomy: outcomes from two UK centres. BJU Int 2006, 97:1211-1215.