Prognostic Factors of Papillary Renal Cell Carcinoma: Results From a Multi-Institutional Series After Pathological Review

Herrmann, Edwin; Trojan, Lutz; Becker, Frank; Wülfing, Christian; Schrader, Andres Jan; Barth, Peter; Stöckle, Michael; Hammerschmied, Christine G.; Staehler, Michael; Stief, Christian G.; Haferkamp, Axel; Hohenfellner, Markus; Legal, Wolfgang; Wullich, Bernd; Bolenz, Christian; Klein, Tobias; Noldus, Joachim; Bierer, S. Beth; Hertle, L.; Brenner, W.; Roos, Frederik C.; Michel, Maurice Stephan; Walter, Bernhard; Gerß, Joachim; Otto, Wolfgang; Hartmann, Arndt

doi:10.1016/j.juro.2009.10.026

Cited by 21 publications

(15 citation statements)

References 28 publications

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“…Either both or at least 1 of these variables has been reported as predictors of outcome in a recently published large series of papillary RCCs [14–17]. In addition to the results of our study, the aforementioned series highlight the importance of T stage and Fuhrman grade in defining the prognosis of patients with papillary RCC.…”

Section: Discussionsupporting

confidence: 74%

“…In addition to the results of our study, the aforementioned series highlight the importance of T stage and Fuhrman grade in defining the prognosis of patients with papillary RCC. Moreover, variables such as patient’s age, sex, and multifocality were consistently irrelevant for prognosis in ours and other studies [14–16]. Finally, another pathologic feature that has gained attention recently as a putative prognosticator of outcome is the subtype of papillary RCC, according to the classification of Delahunt and Eble [18].…”

Section: Discussionmentioning

confidence: 53%

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Immunoexpression status and prognostic value of mammalian target of rapamycin and hypoxia-induced pathway members in papillary cell renal cell carcinomas

Chaux¹,

Schultz²,

Albadine³

et al. 2012

Human Pathology

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Summary Dysregulation of the mammalian target of rapamycin and hypoxia-induced pathways has been consistently identified in clear cell renal cell carcinomas. However, experience with non–clear cell renal cell carcinoma subtypes is scant. In this study, we evaluated the immunohistochemical expression of upstream (PTEN and phosphorylated AKT) and downstream (phosphorylated S6 and 4EBP1) effectors of the mammalian target of rapamycin pathway, as well as related cell-cycle proteins (p27 and c-MYC), and a member of the hypoxia-induced pathway (HIF-1α) in 54 patients with papillary renal cell carcinoma treated by nephrectomy. PTEN was lower in tumor than in normal kidney, and loss of PTEN expression was found in 48% of the patients. In tumor tissues, phosphorylated S6, 4EBP1, and HIF-1α were higher than in normal kidney. Conversely, scores of p27 were lower in tumor than in normal kidney. Finally, scores of c-MYC and phosphorylated AKT were similar in tumor and in normal kidney. Overall mortality and cancer-specific mortality were 24% and 11%, respectively. Tumor progression was observed in 17% of the patients. None of the tested biomarkers predicted cancer-specific mortality or tumor progression. As expected, patients with high T-stage tumors had higher hazard ratios for cancer-specific mortality (hazard ratio, 6.9) and tumor progression (hazard ratio, 6.7). Patients with higher Fuhrman grades also had higher risks for cancer-specific mortality (hazard ratio, 11.4) and tumor progression (hazard ratio, 4.5). In summary, our study provides evidence of dysregulation of the mammalian target of rapamycin and hypoxia-induced pathways in papillary renal cell carcinoma. Immunohistochemistry for members of the mammalian target of rapamycin pathway and for HIF-1α lacked prognostic significance in our cohort.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 53%

Immunoexpression status and prognostic value of mammalian target of rapamycin and hypoxia-induced pathway members in papillary cell renal cell carcinomas

Chaux¹,

Schultz²,

Albadine³

et al. 2012

Human Pathology

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“…pT1a and pT1b; pT2a and pT2b; and pT3a and pT3b), and the classification did not predict RFS and CSS in multivariable analysis once adjusted for the other covariates. Previous studies had addressed the prognostic role of the previous version of the pathological stage of the primary tumour in pRCC series, showing an independent predictive role for 2002 T stage [4,8,10,12,13,20,21]. However, all of the studies clustered localized and locally advanced pRCC into two subgroups (pT1–2 vs pT3–4), again emphasizing the inadequacy of the staging system generated for ccRCC in stratifying the outcome of pRCC.…”

Section: Discussionmentioning

confidence: 99%

“…Cancer‐specific survival (CSS) estimates at 5 years were reported in the range 70–87% for pRCC [4,6–8,10–13], with stage and grade being the most recognized prognostic factors, although several studies provided conflicting results. The prognostic role of tumour subtype is controversial, with some studies supporting it [9,10] and many others refuting it [4,7,8,13].…”

Section: Introductionmentioning

confidence: 99%

Prognostic factors in a large multi‐institutional series of papillary renal cell carcinoma

et al. 2011

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Study Type – Prognosis cohort series (multi‐centre) Level of Evidence 2b What's known on the subject? and What does the study add? The relatively low prevalence of papillary RCC and the limited number of patients enrolled in most of the surgical series limit meaningful conclusions with respect to cancer‐related outcome and independent prognostic information. Patients with papillary RCC have relatively a low risk of tumour recurrence and cancer‐related death after surgery. Pathological lymph node stage, presence of metastases and Fuhrman nuclear grade were the main independent predictors of cancer‐related outcomes, whereas only a non‐statistically significant trend was found for the 2009 pathological T stage. OBJECTIVES To investigate cancer‐related outcomes and prognostic factors of papillary renal cell carcinoma (pRCC) in a large multicentre data set. Oncological outcome and prognostic factors of pRCC have been limitedly evaluated in comparison with the most common RCC subtype, clear cell RCC. PATIENTS AND METHODS From a multicentre retrospective database, including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007, 577 patients with pRCC were identified. Univariable and multivariable Cox regression models were performed to identify prognostic factors predictive of recurrence‐free survival (RFS) and cancer‐specific survival (CSS) after surgery. RESULTS At a median (interquartile range) follow‐up of 39.2 (21.7–72) months, 81 (14%) patients had experienced disease progression and 63 (11%) patients had died from disease; the 5‐year RFS estimate was 85.5%. In multivariable analysis, pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007) and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of RFS; the 5‐year CSS estimate was 87.9%. In Cox multivariable analysis, an independent predictive role was reconfirmed for mode of presentation (pooled P= 0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P= 0.049) and Fuhrman nuclear grade (pooled P= 0.037). CONCLUSIONS Patients with pRCC have a low risk of tumour recurrence and cancer‐related death after surgery. Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS, whereas only a non‐statistically significant trend was found for the 2009 pathological T stage.

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“…Previous studies suggest that pRCC is associated with a lower risk of renal vein or IVC extension [23] and that patients with pRCC of pT3 or greater at baseline have an unfavourable prognosis [24]. Another study of 2157 patients, including 245 with pRCC and 1912 with cRCC, found that pRCC patients with a venous tumour thrombus experienced significantly lower CSS rates compared to cRCC patients, and also that the presence of a venous tumour thrombus was an independent prognostic factor for pRCC but not for cRCC [11].…”

Section: Discussionmentioning

confidence: 99%

Type II papillary histology predicts poor outcome in patients with renal cell carcinoma and vena cava thrombus

Kim¹,

You²,

Jeong³

et al. 2012

BJU International

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E 6 7 3What ' s known on the subject? and What does the study add? In patients with pRCC, the presence of venous tumour thrombus is known to be a predictor of poorer outcomes. However, a paucity of data is available regarding the prognostic signifi cance of histology in patients with RCC and IVC thrombus.In our series, we found that patients with type II pRCC had signifi cantly poorer outcomes when compared to those with cRCC. Although the lack of effective treatment for patients with metastatic pRCC may have contributed to these adverse outcomes, type II papillary histology was independent predictor not only of CSS but also of RFS. OBJECTIVE• To analyze the prognostic impact of papillary histology on oncological outcomes in patients with renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus. PATIENTS AND METHODS• We reviewed the medical records of 74 patients who underwent radical nephrectomy and IVC thrombectomy between 1990 and 2010 for clear cell or papillary RCC.• We compared the clinicopathological features and clinical outcomes of 62 patients with clear cell RCC (cRCC) and 12 with papillary RCC (pRCC).• All cases of pRCC were subdivided into type I or type II.• The prognostic role of papillary histology on recurrence-free survival (RFS) and cancer-specifi c survival (CSS) was estimated using Cox ' s regression models. RESULTS• Upon reclassifi cation of the pRCC subtype, all 12 patients with pRCC had type II tumours.• Patients with type II pRCC were signifi cantly younger ( P = 0.028) and were more probably women ( P = 0.025) than those with cRCC • The 2-and 5-year CSS rates were 81.1% and 53.6% in cRCC patients, and 28.1% and 0% in type II pRCC patients, respectively. All eight patients with non-metastatic type II pRCC developed disease recurrence at a median interval of 6 months after surgery, whereas 25 of 44 (56.8%) patients with non-metastatic cRCC experienced such recurrence at a median interval of 10 months after surgery.• Patients with type II pRCC showed signifi cantly lower CSS ( P < 0.001) and RFS ( P = 0.002) than those with cRCC.• On multivariate analysis, type II papillary histology was an independent predictor of CSS (hazard ratio, 3.73; P = 0.003) and RFS (hazard ratio, 3.15; P = 0.015). CONCLUSIONS• Type II papillary histology appears to be predominant in cases of pRCC with IVC thrombus.• Patients with type II pRCC who presented with IVC thrombus had signifi cantly worse outcomes than those with cRCC, and histology is an important prognostic factor in patients with RCC and IVC thrombus. KEYWORDSinferior vena cava , nephrectomy , renal cell carcinoma , thrombosis Study Type -Prognosis (case series) Level of Evidence 4

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Prognostic Factors of Papillary Renal Cell Carcinoma: Results From a Multi-Institutional Series After Pathological Review

Cited by 21 publications

References 28 publications

Immunoexpression status and prognostic value of mammalian target of rapamycin and hypoxia-induced pathway members in papillary cell renal cell carcinomas

Immunoexpression status and prognostic value of mammalian target of rapamycin and hypoxia-induced pathway members in papillary cell renal cell carcinomas

Prognostic factors in a large multi‐institutional series of papillary renal cell carcinoma

Type II papillary histology predicts poor outcome in patients with renal cell carcinoma and vena cava thrombus

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