Das lokal begrenzte Nierenkarzinom – Bildgebung in Diagnose und Nachsorge: Wieviel ist nötig? Bernd J. Schmitz-Dräger Fürth

Primärdiagnose Urol J. 2012 Fall;9(4):662-6. Pre-operative imaging may overestimate the kidney tumor size. Nasseh HR, Falahatkar S, Ghanbari A, Bagheri Chenari H. Urology Research Center, Razi Hospital, Guilan University of Medical Sciences, Guilan, Iran. Nasseh_hamid@yahoo.com PURPOSE: To compare the kidney tumor size on radical nephrectomy pathology specimen with size estimated by computed tomography (CT) scan and ultrasonography. MATERIALS AND METHODS: The tumor size on pathology specimen of 40 patients who had undergone radical nephrectomy at our center from March 2003 until March 2009 was compared with pre-operative CT scan and ultrasonography findings. The paired t test was used to compare the means. RESULTS: The participants included 40 patients, 25 men and 15 women, with the mean age of 64.12 ± 10.75 years (range, 42 to 79 years). All tumors were renal cell carcinoma. Mean tumor size on pathology specimen was 6.2 ± 1.1 cm. Mean tumor size estimated by pre-operative CT scan and ultrasonography was 7.34 ± 1.83 cm and 7.4 ± 1.96 cm, respectively (P = .001). Tumor stage did not affect this significant difference. There was not any significant difference between tumor size estimated by CT scan or ultrasonography (P = .39). CONCLUSION: Computed tomography scan and ultrasonography both may overestimate renal tumor size. This point must be considered in clinical staging and treatment selection. Multicenter prospective comparison is suggested. Urologenportal 2

Primärdiagnostik: klinische Fragen Erkennung einer Raumforderung Diskriminierung zwischen benigner/maligner Raumforderung Größe und Lage Nierenvenenbefall Infiltration von Nachbarorganen (Nebennieren/Leber) Gefäßversorgung der Niere Funktion&Morphologie der kontralateralen Niere Lymphknoten-/Fernmetastasen 3

Primärdiagnostik: klinische Fragen CT und MRI sind in der Primärdiagnostik des Nieren-tumors gleichwertig. Beide Verfahren erlauben keine Abgrenzung des Onko-zytoms und des fett-armen Angiomyolipoms von malig-nen Tumoren (LoE: 3). Evtl. PET-CT Urologenportal Empfehlung: A Ljungberg B et al. EAU Leitlinie 2013 4

Primärdiagnostik: Maligne oder benigne? 815 konsekutive Patienten mit Nierentumorresektion wegen Tumoren <7 cm Durchmesser ohne Metastasen oder Gefäßinvasion Histologie n % Maligne Tumoren 681 83,6 Oncocytoma 87 10,6 Angiomyolipom 17 2 Nierenzysten 10 1,2 Zystisches Nephrom 5 0,6 Metanephrisches Adenom 8 1 Andere 7 0,9 J Urol. 2006 Dec;176(6 Pt 1):2391-5; discussion 2395-6. Incidence of benign lesions for clinically localized renal masses smaller than 7 cm in radiological diameter: influence of sex. Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P. Department of Urology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. PURPOSE: We determined the incidence of benign renal lesions in patients undergoing definitive surgery for localized renal masses 7 cm or less in maximum radiological diameter, and assessed preoperative and clinical parameters associated with benign histology. MATERIALS AND METHODS: The records of 1,184 patients who underwent consecutive partial or radical nephrectomies between January 2000 and January 2005 were retrospectively reviewed. We excluded 208 patients with lesions more than 7 cm in maximum radiological diameter, 17 with evidence of renal vein or vena caval invasion, 75 with suspected or documented metastatic disease, 28 with a history of renal cell carcinoma and 41 with no available imaging. Logistic regression was done to determine clinical factors associated with benign renal masses, including radiological tumor size, cystic vs solid appearance, patient sex, age, presenting symptoms and race. RESULTS: Of 815 nephrectomies in our data set 134 (16.4%) were associated with benign lesions, including oncocytoma in 87 (10.7%), angiomyolipoma in 17 (2%), simple cysts in 10 (1.2%), metanephric adenoma in 8 (1%), cystic nephroma in 5 (0.6%) and other in 7. On multivariate logistic regression analysis only sex was significantly associated with benign histology with females having an OR of 1.8 (95% CI 1.2 to 2.6, p = 0.002). Tumor size was not independently associated with benign histology (p = 0.13). CONCLUSIONS: A significant number (16.4%) of benign lesions less than 7 cm in radiological diameter were operated on based on suspicious preoperative imaging. Women had almost twice the likelihood of having a benign lesion. Snyder ME et al. J Urol 2006 5

Zystische Raumforderung der Nieren Nierenzysten Bosniak >3 sollten operativ behandelt werden. LoE 3 Empfehlung C Ljungberg B et al. EAU Guidelines 2013 6

Die Rolle des PET-CT ist ungeklärt MRT vs. CT Unklarer CT-Befund Schwangerschaft KM-Allergie Vena cava-Befall Die Rolle des PET-CT ist ungeklärt Urologenportal Ljungberg B et al. EAU Leitlinie 2013 7

Primärdiagnostik: klinische Fragen Die Darstellung der Gefäßversorgung erfolgt bevorzugt durch die Kontrast-verstärkte biphasische CT-Angiographie. Bei bekannter KM-Allergie kann alternativ eine biphasische MRT- Angiographie (MRA) erfolgen. but less sensitive and accurate than CT angiography for detecting supernumerary vessels (22). Ljungberg B et al. EAU Leitlinie 2013 8

T-Staging – Präzision der Bildgebung Tumorgröße im CT/ Ul-traschall um ca. 20% überschätzt cT4-Diagnose im CT: Overstaging in 60% der Fälle! Urol J. 2012 Fall;9(4):662-6. Pre-operative imaging may overestimate the kidney tumor size. Nasseh HR, Falahatkar S, Ghanbari A, Bagheri Chenari H. Urology Research Center, Razi Hospital, Guilan University of Medical Sciences, Guilan, Iran. Nasseh_hamid@yahoo.com PURPOSE: To compare the kidney tumor size on radical nephrectomy pathology specimen with size estimated by computed tomography (CT) scan and ultrasonography. MATERIALS AND METHODS: The tumor size on pathology specimen of 40 patients who had undergone radical nephrectomy at our center from March 2003 until March 2009 was compared with pre-operative CT scan and ultrasonography findings. The paired t test was used to compare the means. RESULTS: The participants included 40 patients, 25 men and 15 women, with the mean age of 64.12 ± 10.75 years (range, 42 to 79 years). All tumors were renal cell carcinoma. Mean tumor size on pathology specimen was 6.2 ± 1.1 cm. Mean tumor size estimated by pre-operative CT scan and ultrasonography was 7.34 ± 1.83 cm and 7.4 ± 1.96 cm, respectively (P = .001). Tumor stage did not affect this significant difference. There was not any significant difference between tumor size estimated by CT scan or ultrasonography (P = .39). CONCLUSION: Computed tomography scan and ultrasonography both may overestimate renal tumor size. This point must be considered in clinical staging and treatment selection. Multicenter prospective comparison is suggested. Margulis V et al Nasseh H et al., Urol J 2012; Margulis V et al., Cancer 2007 9

Thorax in 2 Ebenen als Minimaldiagnostik M-Staging CT Thorax Thorax in 2 Ebenen als Minimaldiagnostik Knochenszintigramm oder CT-Schädel bei klinischem Verdacht auf Metastasen (aP, Schmerzen) Empfehlung: A Ljungberg B et al. EAU Leitlinie 2013 10

Active Surveillance Indikation: Ältere und/oder multimorbide Patienten mit kleinen Tumoren Friederikenstift LoE: 3 Ljungberg B et al. EAU Leitlinie 2013 11

Medianer Durchmesser 2 cm Mediane Nachbeobachtung 2 Jahre Active Surveillance 154 Patienten mit 172 Tumoren Medianer Durchmesser 2 cm Mediane Nachbeobachtung 2 Jahre Inverse Korrelation zwischen initialer Größe und Wachstum Intervention bei 68/172 Tumoren (39%) Davon 84% maligne Metastasen bei 2/154 Patienten (1,3%) LoE: 3 Crispen PL, et al. Cancer 2009 12

Active Surveillance Parameter Fortsetzung AS Intervention p Alter (J) (Median) 74 (35 – 87) 66 (35 – 88) .0001 Geschlecht (m) (%) 73 71 .856 Durchmesser bei Diagnose (cm) (Median) 2 (0,8 – 9) 2 (0,4 – 12) .442 Dauer Follow-up (Monate) 29 (12 – 156) 21 (12 – 96) .0007 Wachstum cm/Jahr (Median) 0,17 (-0,63 – 2,47) 0,26 (-1,4 – 1,6) .023 Wachstum (%) (Median) 6,9 (-25 – 75) 12,8 (-42 – 160) .015 LoE: 3 Crispen PL, et al. Cancer 2009 13

Bildgebung in der Tumornachsorge Postoperative Komplikationen Nierenfunktion Lokalrezidiv nach Heminephrektomie oder Ablation Rezidiv in der kontralateralen Niere Lymphknoten-/Fernmetastasen J Urol. 1996 Jun;155(6):1868-73. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. Lerner SE, Hawkins CA, Blute ML, Grabner A, Wollan PC, Eickholt JT, Zincke H. Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA. PURPOSE: We investigated the outcome of nephron sparing surgery in patients with low grade and low stage (Robson stage II or less) renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 185 patients treated with nephron sparing surgery and 209 matched for patient age and sex, and tumor stage and grade who were treated with radical nephrectomy. Kaplan-Meier survival curves were constructed for progression and survival end points. Multivariate analysis was performed to determine the tumor characteristics independently correlated with progression and cancer death. RESULTS: No significant difference was observed with respect to progression-free, crude or cancer specific survival between the nephron sparing surgery and radical nephrectomy groups. Less than 5% of the patients treated with conservative nephron sparing surgery had local recurrence. Tumor size was a strong independent predictor of outcome, whereas Robson stage was not. Patients treated with radical nephrectomy had a significant cancer specific and progression-free survival advantage when controlling for tumor diameter and grade. However, no difference was observed in patients with primary tumor diameters of 4 cm. or less. CONCLUSIONS: Robson staging is inaccurate in predicting tumor behavior. Patients with tumors larger than 4 cm. and a normal contralateral kidney may be best served by radical nephrectomy rather than elective nephron sparing surgery. However, nephron sparing surgery may result in an outcome similar to that of radical nephrectomy for low grade, low stage renal cell carcinomas of 4 cm. or smaller. Cancer. 2008 Jul 1;113(1):84-96. doi: 10.1002/cncr.23520. Survival rates after resection for localized kidney cancer: 1989 to 2004. Russo P, Jang TL, Pettus JA, Huang WC, Eggener SE, O'Brien MF, Karellas ME, Karanikolas NT, Kagiwada MA. Urology Service, Department of Surgery, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. russop@mskcc.org BACKGROUND: Mortality rates from kidney cancer have continued to rise despite increases in the detection of smaller renal tumors and rates of renal surgery. To explore the factors associated with this treatment-outcome discrepancy, the authors evaluated how changes in tumor size have affected disease progression in patients after nephrectomy for localized kidney cancer, and they sought to identify the factors associated with disease progression and overall patient survival after resection for localized kidney cancer. METHODS: In total, 1618 patients with localized kidney cancer were identified who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center from 1989 to 2004. Patients were categorized by year of surgery: from 1989 to 1992, from 1993 to 1996, from 1997 to 2000, and from 2001 to 2004. Tumor size was classified according to the following strata: <2 cm, from 2 cm to 4 cm, from 4 cm to 7 cm, and >7 cm. Disease progression was defined as the development of local recurrence or distant metastases. Five-year progression-free survival (PFS) was calculated for patients in each tumor size strata according to the year of operation using the Kaplan-Meier method. The patient-, tumor-, and surgery-related characteristics associated with PFS and overall survival (OS) were explored using univariate analysis, and all significant variables were retained in a multivariate Cox regression analysis. RESULTS: Overall, the number of nephrectomies increased for all tumor size categories from 1989 to 2004. A tumor size migration was evident during this period, because the proportion of patients with tumors <2 cm and with tumors from 2 cm to 4 cm increased, whereas the proportion of patients with tumors >7 cm decreased. One hundred seventy-nine patients (11%) developed disease progression after nephrectomy. Sixteen patients (1%) developed local recurrences, and 163 patients (10%) developed distant metastases. When 5-year PFS was calculated for each tumor size strata according to 4-year cohorts, trends in PFS did not improve or differ significantly over time. Compared with historic cohorts, patients in more contemporary cohorts were more likely to undergo partial nephrectomy rather than radical nephrectomy and were less likely to undergo concomitant lymph node dissection and adrenalectomy. Multivariate analysis demonstrated that pathologic stage and tumor grade were associated with disease progression, whereas patient age and tumor stage were associated with overall patient survival. CONCLUSIONS: Despite an increasing number of nephrectomies and a size migration toward smaller tumors, trends in 5-year PFS and OS did not improve or differ significantly over time. These findings require further research to identify causative mechanisms, and they argue for the consideration of active surveillance for patients who have select renal tumors and a re-evaluation of the current treatment paradigm of surgically removing solid renal masses on initial detection. 14

Nierenfunktion Vor der Therapieentscheidung Abklärung der Nierenfunktion soweit eine Funktionseinschränkung vermutet wird. Empfehlung: B Ljungberg B et al. EAU Leitlinie 2013 15

Nierenfunktion Gute Korrelation zwischen funktionellem Nierenparenchym-Volumen im CT und (99m)Tc – DTPA-Scan Nur untersucht für chronische Obstruktion! Morrisroe SN et al. J Urol 2010; Sarma D et al., Indian J Urol J 2012 16

Nachsorge - Prinzipien Eine Rezidivsuche ist nur dann sinnvoll, wenn eine therapeutische Konsequenz gezogen werden kann! Die Bedeutung des Rezidivnachweises hat mit der Einführung der TT eine neue Bedeutung erlangt. Ziel der Rezidivsuche ist ein Tumornachweis, so lange eine operative Entfernung möglich ist. Ansonsten Beschränkung auf (Erhalt der) Nierenfunktion 17

Nachsorge – Empfehlungen I Ein Rö-Thorax in 2E sollte wegen geringer Sensitivität beim der Diagnose kleiner Lungenfiliae nicht erfolgen. Ultraschall sollte auf Grund einer begrenzten Sensitivität nicht als alleiniges bildgebendes Verfahren genutzt werden. PET/ PET-CT und Knochenszintigramm sind wegen geringer Sensitivität und Spezifität keine Standardverfahren Ljungberg B et al. EAU Leitlinie 2013 18

Bildgebung in der Tumornachsorge Lokalrezidiv nach Organ-erhaltender Tumorresektion Scand J Surg. 2004;93(2):126-31. Nephron-sparing surgery--strategies for partial nephrectomy in renal cell carcinoma. Ljungberg B. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden. Borje.Ljungberg@urologi.umu.se The use of partial nephrectomy for renal cell carcinoma has continuously changed in the clinical practice. Previously it was mostly used in imperative cases, in patients with a solitary kidney or in patients with a risk of renal failure. An increased number of incidentally detected renal cell carcinomas are diagnosed due to the advances of the radiological methods. These tumours tend to be smaller and generally with a lower stage. The reported excellent results of partial nephrectomy have promoted the use of nephron-sparing surgery also in patients with a normal contralateral kidney and tumours smaller than 4-5 cm. The technical outcome is excellent with a low operative morbidity and a good oncologic control. Therefore partial nephrectomy has become a standard technique in the treatment of properly selected patients. Laparoscopy with its reduced postoperative pain and shorter rehabilitation time, has encouraged the interest in minimally invasive nephron sparing surgical techniques. Although low, the risk of local tumour recurrence and surgical complications are higher after nephron-sparing surgery compared with radical nephrectomy. Furthermore, long-term renal function remains adequate in most patients with a normally functioning contralateral kidney also after radical nephrectomy. Albeit these facts, there is convincing evidence justifying nephron-sparing surgery to be used routinely for patients with a small renal cell carcinoma and a normal functioning contralateral kidney. Ljungberg B. Scand J Surg 2004 19

Nachsorge – Empfehlungen II Ljungberg B et al. EAU Leitlinie 2013 20

Risiko-stratifizierte Nachsorge - Algorithmus Keine Empfehlung für Active Surveillance! Empfehlung: C Ljungberg B et al. EAU Leitlinie 2013 21

Vielen Dank!