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

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.

     

Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study

Study Type – Therapy (multi‐centre retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT‐UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the ‘gold‐standard’ treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT‐UCs. Due to the paucity of cases of UUT‐UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi‐institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5‐year probability of cancer‐specific survival, recurrence‐free survival and metastasis‐free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases.

OBJECTIVE

• ? To compare recurrence‐free survival (RFS), metastasis‐free survival (MFS) and cancer‐specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT‐UC) located in the ureter.

PATIENTS AND METHODS

• ? We performed a multi‐institutional retrospective review of patients with UUT‐UC who had undergone RNU or SU between 1995 and 2010.
• ? Type of surgery, Tumour‐Node‐Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival.

RESULTS

• ? In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow‐up was 26 (10–48) months.
• ? The 5‐year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P= 0.99); 37% and 47.9%, respectively (P= 0.48); 81.9% and 85.4%, respectively (P= 0.51).
• ? In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P= 0.94, 0.42 and 0.53, respectively).
• ? In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P= 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P= 0.001, 0.04, 0.009 and 0.001, respectively).
• ? The main limitation of the study is its retrospective design, which is due to the rarity of the disease.

CONCLUSIONS

• ? Short‐term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases and should be considered an option.
• ? In every other case, RNU still represents the ‘gold standard’ for the treatment of UUT‐UC.

     

Unclassified renal cell carcinoma: a report of 56 cases

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Unclassified RCC represents 0.7–5.7% of renal tumours. Limited reported data from two series suggests that unclassified RCC is an aggressive form of RCC, mainly because most cases are at an advanced stage at presentation, but overall and cancer‐specific survival were not significantly different between unclassified and clear‐cell RCC in an additional series of 38 patients. Our study of 56 cases of unclassified RCC describes the pathological features that can be applied to predict prognosis on a daily basis. In particular nuclear grade, TNM classification, tumour coagulative necrosis, tumour size, microvascular invasion and 2004 WHO histotype are independent predictors of disease‐free and cancer‐specific survival.

OBJECTIVE

• ? To evaluate the clinicopathological features and outcomes of 56 patients with unclassified renal cell carcinoma (RCC) meeting 2004 World Health Organization diagnostic criteria.

PATIENTS AND METHODS

• ? Urological pathology files of the participating institutions were reviewed and cases of unclassified RCC that met the inclusion criteria were retrieved.
• ? Nuclear grade, pT status, tumour size, regional lymph node involvement, distant metastases, coagulative tumour necrosis, mucin and sarcomatoid differentiation were evaluated in radical nephrectomy or nephron‐sparing specimens.
• ? Significant factors in univariate analysis were then assessed by a multivariate analysis of independent prognostic factors using Cox proportional hazard regression analysis.

RESULTS

• ? Fifty‐six cases met the histological criteria for unclassified RCC. Thirty‐four (61%) cases were categorized as unrecognizable cell type (mean overall survival 47 months; median 36 months), 20 (36%) as composites of recognized types (mean overall survival 36 months; median 26 months), and two (4%) (mean survival 16 months; median 16 months) as pure sarcomatoid morphology without recognizable epithelial elements.
• ? Cox multivariate analysis showed nuclear grade (P= 0.020), stage (P < 0.001), tumour coagulative necrosis (P= 0.018), tumour size (P < 0.001), microvascular invasion (P < 0.001) and tumour histotype (P= 0.028) to be independent predictors of disease‐free survival, with tumour size being the most significant (hazard ratio [HR] 9.068, 95% confidence interval [CI] 3.231–25.453).
• ? Nuclear grade (P= 0.026), stage (P < 0.001), tumour coagulative necrosis (P < 0.001), tumour size (P= 0.044), microvascular invasion (P < 0.001), tumour recurrence after surgery (P < 0.001) and tumour histotype (P= 0.056) were independent predictors of cancer‐specific survival, with tumour recurrence after surgery being the most significant (HR 14.713, 95% CI 5.329–40.622).

CONCLUSION

• ? The prognosis of patients with unclassified RCC seems to be related to clinicopathological features known to be relevant in common forms of RCC.

     

Prognostic role of ECOG performance status in patients with urothelial carcinoma of the upper urinary tract: an international study

Study Type – Prognosis (inception cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? ECOG Performance Status has gained wide popularity as an integral part of the assessment of patients with upper urinary tract carcinoma. Our findings indicate that ECOG‐PS is strongly associated with perioperative and overall survival and should be considered carefully in our decision‐making process.

OBJECTIVE

• ? To evaluate the prognostic role of ECOG Performance status (ECOG‐PS) in a large multi‐institutional international cohort of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.

MATERIALS AND METHODS

• ? Data of 427 patients treated with radical nephroureterectomy at five international institutions in Asia, Europe and Northern America were collected retrospectively from 1987 to 2008.
• ? Logistic and Cox regression models were used for univariable and multivariable analyses.

RESULTS

• ? ECOG‐PS was 0 in 272 of 427 (64%) patients. The median follow‐up of the whole cohort was 32 months.
• ? The five‐year recurrence‐free (RFS), cancer‐specific (CSS) and overall (OS) survival estimates were 71.7%, 74.9% and 68.5%, respectively, in patients with ECOG‐PS 0 compared with 60.1%, 67.8%, and 51.4% respectively, in patients with ECOG‐PS ≥1 (P value 0.08 for RFS, 0.43 for CSS, and <0.001 for OS, respectively).
• ? On multivariable Cox regression analyses, ECOG‐PS was not an independent predictor of either RFS (hazard ratio 1.4; P = 0.107) or CSS (hazard ratio 1.2; P = 0.426) but was an independent predictor of OS (hazard ratio 1.5; P = 0.03).

CONCLUSIONS

• ? In this large multicentre international study, ECOG‐PS was not significantly associated with RFS and CSS.
• ? Conversely we find a strong association with survival 1‐month after surgery and OS. Further research is needed to ascertain the additive prognostic role of ECOG‐PS in well‐designed prospective multicentre studies.

     

Impact of comorbidity on complications after nephrectomy: use of the Clavien Classification of Surgical Complications

Study Type – Retrospective (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Tumour characteristics, physical status and comorbidities are considered important for surgical outcome and prognosis. The present study objectively evaluates the association between comorbidity and postoperative complications after nephrectomy for RCC, by using the modified Clavien Classification of Surgical Complications to grade complications after nephrectomy.

OBJECTIVE

• ? To present a single‐centre experience of open nephrectomy for lesions suspected for renal cell carcinoma (RCC), evaluating the association between comorbidity and postoperative complications using a standardized classification system for postoperative complications.

PATIENTS AND METHODS

• ? Clinicopathological data of 198 patients undergoing open radical or partial nephrectomy for lesions suspected of RCC were retrospectively analysed.
• ? Comorbidity scored by the Charlson comorbidity index (CCI), body mass index, age, gender, surgical procedure and surgical history were examined as predictive factors for postoperative complications, which were scored using the modified Clavien Classification of Surgical Complications (CCSC).

RESULTS

• ? The overall complication rate was 34%: 7% grade I, 15% grade II, 5% grade III, 3% grade IV and 4% grade V. Preoperative comorbidities were present in 51% of all patients.
• ? There were significantly more major complications (CCSC >2) in patients with major comorbidities (CCI >2), at 16% vs 7% (P= 0.018).
• ? Patients with high‐stage RCC had significantly more severe complications than low‐stage RCC (P= 0.018).
• ? In multivariable analysis, comorbidity (odds ratio [OR] 7.55, P= 0.004) and tumour stage 3–4 (OR 6.23, P= 0.007) were independent predictive factors for major complications.

CONCLUSIONS

• ? Major complications occur significantly more often when major comorbidities are present.
• ? Comorbidity scores can be used in risk stratification for complications and should be considered during decision‐making and counselling of patients before nephrectomy.

     

Frequency of regulatory T cells in peripheral blood and in tumour‐infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma

What’s known on the subject? and What does the study add? Treg overexpression has been demonstrated in several neoplasms, including liver, breast, pancreas and melanoma, while it has not been well evaluated in renal cancer. In renal cancer patients versus controls we found an increased expression of these cells, especially in tumour‐infiltrating lymphocytes. Moreover, Treg frequency significantly correlated with pathological stage, nuclear grade and prognostic models.

OBJECTIVE

• ? To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination.

PATIENTS AND METHODS

• ? Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane‐CD25 and intracytoplasmic‐Foxp3 expression by flow cytometry.
• ? Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25‐depleted mononuclear cells (MNC) and CD25‐depleted MNC cultured in the presence of purified CD25⁺ Tregs.
• ? Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models.

RESULTS

• ? Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25⁺ cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon‐γ production by CD25‐depleted MNC, thus demonstrating that they are active Tregs.
• ? Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL).

CONCLUSION

• ? Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.

     

Exposed proliferation antigen 210 (XPA-210) in renal cell carcinoma (RCC) and oncocytoma: clinical utility and biological implications

What's known on the subject? and What does the study add? The exposed proliferation antigen 210 (XPA‐210) of the proliferation marker thymidine kinase 1 (TK1) showed higher expression levels in metastatic renal cell carcinoma. The current study used a new XPA‐210 antibody to clarify the role of TK1 tissue expression in the largest reported cohort of different renal cell carcinoma types and oncocytomas.

OBJECTIVE

• ? To determine the clinical role of the exposed proliferation antigen 210 (XPA‐210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC.

PATIENTS AND METHODS

• ? Expressions of XPA‐210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin‐embedded specimens.
• ? Immunohistochemistry was performed with a monoclonal anti‐XPA‐210 antibody. Staining was measured by the percentage of positive cells.
• ? Expression was compared between subgroups and correlated with respective clinical data using one‐way analysis of variance with post hoc Tukey‐Kramer analyses.

RESULTS

• ? XPA‐210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [sem ] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P < 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18).
• ? Subdivided into RCC groups, only ccRCC (mean [sem ] 5.1 [0.6]; P < 0.001) and papRCC (4.4 [0.6]; P < 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not.
• ? RCC XPA‐210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001).

CONCLUSIONS

• ? The malignant character of RCC is reflected by higher XPA‐210 expression as compared with oncocytomas and normal kidney.
• ? The ccRCC and papRCC subgroups had higher XPA‐210 levels.
• ? XPA‐210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC.

     

High cytoplasmic expression of p27(Kip1) is associated with a worse cancer-specific survival in clear cell renal cell carcinoma

What's known on the subject? and What does the study add? The loss of p27^Kip1 correlates with poor prognosis in various human cancers, and was postulated as a biomarker in RCC. Up to now p27^Kip1 analysis in RCC was focused on its nuclear localization. We confirmed higher p27^Kip1 expression in the nucleus and cytoplasm of RCC and correlated high cytoplasmic p27^Kip1 with an unfavourable clinic and a reduced survival.

OBJECTIVES

• ? To analyse the cytoplasmic and nuclear differences of p27^Kip1 expression and localization in benign and clear cell renal cell carcinoma (ccRCC) with regard to overall survival (OS) and cancer‐specific survival (CSS).
• ? p27^Kip1 is considered to contribute to the progression of ccRCC and is targeted by next generation dual‐therapies.

PATIENTS AND METHODS

• ? In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27^Kip1 by immunohistochemistry using a tissue microarray technique.
• ? Staining intensity and percentage of positive stained cells are given as expression scores. p27^Kip1 expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue.
• ? Differences in OS and CSS were analyzed by log‐rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher's exact test.

RESULTS

• ? Cytoplasmatic (mean [sd ]: 13.8% [1.2%] vs 10.7% [1.7%]; P= 0.04) and nuclear (mean [sd ]: 75.6% [2.7%] vs 13.6% [2.1%]; P < 0.001) staining of p27^Kip1 were significantly stronger in ccRCC tissues compared to benign tissue.
• ? High cytoplasmic p27^Kip1 expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease (P < 0.001).
• ? The median follow‐up time was 38.2 months.
• ? There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27^Kip1 (P < 0.001) and CSS heavily tended to be lower in the nuclear low expression group (P= 0.069).

CONCLUSIONS

• ? High cytoplasmic p27^Kip1 levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial.
• ? The present study corroborates the consideration of cytoplasmic p27^Kip1 for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27^Kip1 from the cytoplasm to the nucleus.

     

Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pT1 clear-cell renal cell carcinoma

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three‐dimensional tumour volume (cm³) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC‐specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC.

OBJECTIVE

• ? To address whether information on three‐dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone.

PATIENTS AND METHODS

• ? We identified 955 patients treated with radical nephrectomy or nephron‐sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non‐cystic clear‐cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients.
• ? We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis.
• ? Univariate and multivariable associations with RCC‐specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS

• ? Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30–15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83–7.85; P= 0.10).
• ? Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients.
• ? Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC‐specific death were similar.
• ? Multivariable adjustment did not alter our findings.

CONCLUSIONS

• ? Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC.
• ? Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.

     

Evolution of the clinical presentation of men undergoing radical prostatectomy for high-risk prostate cancer

Study Type – Prognosis cohort series (multi‐centre) Level of Evidence 4 What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at a higher rate in the prostate cancer population. This study adds greater than 20‐year data regarding the continued evolution of high‐risk prostate cancer toward high‐Gleason disease as the sole determinant of high‐risk status prior to radical prostatectomy. It validates the accumulation of multiple‐risk factors as a poor prognostic indicator in a radical prostatectomy population and demonstrates long‐term cancer specific outcomes, extending the findings demonstrated by previous publications.

OBJECTIVE

• ? To investigate the outcomes and potential effect of improved longitudinal screening in men presenting with high‐risk (advanced clinical stage [>T2b], Gleason score 8–10 or prostate‐specific antigen [PSA] level >20 ng/mL) prostate cancer (PC).

PATIENTS AND METHODS

• ? The Institutional Review Board approved, Institutional Radical Prostatectomy Database (1992–2010) was queried for men with high‐risk PC based on D'Amico criteria.
• ? Year of surgery was divided into two cohorts: the Early PSA Era (EPE, 1992–2000) and the Contemporary PSA Era (CPE, 2001–2010).
• ? PC features and outcomes were evaluated using appropriate comparative tests.

RESULTS

• ? In total, 667 men had high‐risk PC in the EPE and 764 in the CPE.
• ? In the EPE, 598 (89.7%) men presented with one high‐risk feature; 173 (29.0%) men had a Gleason score of 8–10 on biopsy. In the CPE, 717 (93.9%) men presented with one high‐risk feature (P= 0.004) and 494 (68.9%) men had a Gleason score of 8–10.
• ? At 10 years, biochemical‐free survival (BFS) was 44.1% and 36.4% in the EPE and CPE, respectively (P= 0.04); metastases‐free survival (MFS) was 77.1% and 85.1% (P= 0.6); and PC‐specific survival (CSS) was 83.3% and 96.2% (P= 0.5).
• ? BFS, MFS and CSS were worse for men with more than one high‐risk feature in both eras.

CONCLUSIONS

• ? Over the PSA era, an increasing percentage of men with high‐risk PC were categorized by a biopsy Gleason score of 8–10.
• ? The accumulation of multiple high‐risk features increases the risk of biochemical recurrence, the development of metastases and death from PC.
• ? BFS, MFS and CSS are stable over the PSA era for these men. The balance between a greater proportion of men having high Gleason disease and a greater proportion with small, less advanced tumours may explain the stability in MFS and CSS over time.

     

Prognostic significance of preoperative kidney volume for predicting renal function in renal cell carcinoma patients receiving a radical or partial nephrectomy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? At present, many studies have been executed to identify predictors for chronic kidney disease or renal insufficiency after radical nephrectomy or partial nephrectomy. We examined whether preoperative kidney volume is a predictor for renal function after radical or partial nephrectomies in RCC patients. To our knowledge, this is the first study to report on the relationship between preoperative kidney volume and changes in renal function in RCC patients who underwent radical nephrectomy or partial nephrectomy performed by one surgeon.

OBJECTIVE

• ? To investigate whether preoperative kidney volume is a prognostic factor for predicting the postoperative glomerular filtration rate (GFR) in renal cell carcinoma (RCC) patients.

PATIENTS AND METHODS

• ? We included 133 patients who underwent radical (n= 83) or partial (n= 50) nephrectomy for RCC.
• ? Kidney parenchymal volume was measured using personal computer‐based software and GFR was estimated before and after surgery at 6 and 12 months.
• ? We evaluated the change in kidney volume after radical and partial nephrectomy and used regression analysis to identify predictors of lower post‐surgical GFR at 12 months.

RESULTS

• ? The mean volume of the normal side kidney for the radical nephrectomy group increased from 142.4 mL to 166.0 mL (17.2%) and 171.5 mL (21.2%) after surgery at 6 and 12 months, respectively.
• ? In the partial nephrectomy group, the volume of the normal side kidney increased from 127.2 mL to 138.8 mL (9.1%) and 140.6 mL (10.9%) after surgery at 6 and 12 months, respectively.
• ? The volume of the operated side kidney decreased from 128.5 mL to 102.3 mL (20.1%) and 101.8 (20.6%) after surgery at 6 and 12 months, respectively.
• ? In the radical nephrectomy group, older age (P < 0.001), preoperative volume of the normal kidney (P= 0.022) and preoperative GFR for the normal side kidney (P= 0.045) were significant predictors of lower post‐surgical GFR at 12 months.
• ? In the partial nephrectomy group, older age (P= 0.001) and preoperative volume for both kidneys (P= 0.037) were significant predictors of lower post‐surgical GFR at 12 months.

CONCLUSION

• ? Preoperative kidney volume is an independent predictor of GFR in RCC patients who underwent radical or partial nephrectomy.

     

Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

• ? To confirm the recurrence‐preventing efficacy and safety of 18‐month bacillus Calmette‐Guérin (BCG) maintenance therapy for non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

• ? The enrolled patients had been diagnosed with recurrent or multiple non‐muscle‐invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT).
• ? The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once‐weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non‐maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence‐free survival (RFS).

RESULTS

• ? Efficacy analysis was performed for 115 of the full‐analysis‐set population of 116 eligible patients, including 41 maintenance group patients, 42 non‐maintenance group patients and 32 epirubicin group patients.
• ? At the 2‐year median point of the overall actual follow‐up period, the final cumulative RFS rates in the maintenance, non‐maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively.
• ? The RFS following TURBT was significantly prolonged in the maintenance group compared with the non‐maintenance group (generalized Wilcoxon test, P= 0.0190).

CONCLUSION

• ? BCG maintenance therapy significantly prolonged the post‐TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

     

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi-institutional study

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Few studies supported the expanded indications for nephron‐sparing surgery (NSS) in selected patients with 4.1 cm renal tumours in the size range (T1b). However, all these comparative studies included both imperative and elective partial nephrectomy and patient selection for analysis was based on pathological stage (pT1) and not on clinical stage (cT1). Patients with clinically organ‐confined RCC (cT1) who are candidates for elective PN have a limited risk of clinical understaging. NSS is not associated with an increased risk of recurrence and cancer‐specific mortality both in cT1a and cT1b tumours

OBJECTIVE

• ? To compare the oncological outcomes of patients who underwent elective partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organ‐confined renal masses ≤7 cm in size (cT1).

PATIENTS AND METHODS

• ? The records of 3480 patients with cT1N0M0 disease were extracted from a multi‐institutional database and analyzed retrospectively.

RESULTS

• ? In patients who underwent PN, the risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases.
• ? With regard to the cT1a patients, the 5‐ and 10‐year cancer‐specific survival (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%, respectively, after PN (log‐rank test: P = 0.01).
• ? With regard to cT1b patients, the 5‐year CSS probabilities were 92.6% after RN and 90% after PN, respectively (log‐rank test: P = 0.89).
• ? Surgical treatment failed to be an independent predictor of CSS on multivariable analysis, both for cT1a and cT1b patients.
• ? Interestingly, PN was oncologically equivalent to RN also in patients with pT3a tumours (log‐rank test: P = 0.91).

CONCLUSIONS

• ? Elective PN is not associated with an increased risk of recurrence and cancer‐specific mortality in both cT1a and cT1b tumours.
• ? Data from the present study strongly support the use of partial nephrectomy in patients with clinically T1 tumours, according to the current recommendations of the international guidelines.

     

Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment‐naïve metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves (P < 0.001), suggesting that MSKCC prognostic factors might be still valid to predict survival in metastatic RCC in the era of molecular targeted therapy.

OBJECTIVES

• ? To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice.
• ? In addition, to investigate the prognostic clinicopathological factors in these patients.

PATIENTS AND METHODS

• ? The present study consisted of native Japanese patients with metastatic RCC, comprising 29 pretreated and 34 systemic treatment‐naïve patients.
• ? Univariate and multivariate analyses were performed by the log‐rank test and the Cox proportional hazards model, respectively.

RESULTS

• ? Estimated median progression‐free survival and overall survival (OS) were 9.3 months (95% confidence interval, CI, 5.0–13.7) and 32.2 months (95% CI, 24.4–40.0), respectively.
• ? Among the patients pretreated before sunitinib, two patients were treated with initialized systemic therapy with sorafenib and the remaining 27 were initialized with interferon‐α.
• ? The OS from the initial systemic therapy of the patients in pretreated groups was 79.6 months (95% CI, 14.6–144.5).
• ? The application of the Memorial Sloan‐Kettering Cancer Center model distinctly separated the OS curves (P < 0.001).
• ? The most common grade 3 adverse events were fatigue (53%), thrombocytopaenia (48%), hand‐foot syndrome (16%), anaemia (20%), hypertension (10%) and leucopaenia (9%), although these events were manageable and reversible.

CONCLUSIONS

• ? Sunitinib has a favourable efficacy/safety profile for Japanese metastatic RCC patients in clinical practice.
• ? The estimated median OS was >2 years with acceptable tolerability.
• ? The median OS from the initial systemic therapy of the pretreated patients was >6 years.
• ? Memorial Sloan‐Kettering Cancer Center prognostic factors still appear to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.

     

Long‐term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long‐term outcomes among men with clinically‐detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen‐detected prostate cancer.

OBJECTIVE

• ? To examine the long‐term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

PATIENTS AND METHODS

• ? Among 42 376 men randomised during the period of the first round of the trial (1993–1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively.
• ? Of these men, 420 (36.5%) screen‐detected and 54 (25.7%) controls underwent RP with long‐term follow‐up data (median follow‐up 9.9 years).
• ? Progression‐free (PFS), metastasis‐free (MFS) and cancer‐specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen‐detected (vs control) was associated with RP outcomes after adjusting for standard predictors.

RESULTS

• ? RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen‐detected cases had significantly lower prostate‐specific antigen (PSA) levels at diagnosis.
• ? Men from the screening arm had a significantly higher PFS (P= 0.003), MFS (P < 0.001) and CSS (P= 0.048).
• ? In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23–0.83, P= 0.011) and metastasis (HR 0.18, 95% CI 0.06–0.59, P= 0.005).
• ? Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms.
• ? Limitations of the present study include lead‐time bias and non‐randomised treatment selection.

CONCLUSIONS

• ? After RP, screen‐detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow‐up time.
• ? The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables.
• ? However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

     

Factors influencing post-recurrence survival in bladder cancer following radical cystectomy

Study Type – Prognosis (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Tumour recurrence following radical cystectomy for bladder cancer generally heralds a grave prognosis. Post‐cystectomy recurrences usually occur within the first 2–3 years, and most patients die within 15 months of recurrence. However, few patients have a more prolonged survival following recurrence. Several studies have identified factors prognostic for bladder cancer recurrence and survival following cystectomy. However, the role of clinicopathological variables in determining patient outcome following bladder cancer recurrence is hitherto undocumented. This is the first retrospective single‐institution study to analyze factors that influence prognosis following bladder cancer soft‐tissue recurrence after radical cystectomy. The investigation identified pathologic stage, lymph node density, type of urinary diversion, time to recurrence after surgery, site of recurrence, and administration of post‐recurrence chemotherapy as independent predictors of post‐recurrence survival. The findings call attention to the importance of pathological assessment at cystectomy, diligent surveillance and post‐recurrence management in ensuring optimal patient outcome following recurrence. It also emphasizes the aggressive nature of invasive bladder cancer when traditional treatment strategies fail.

OBJECTIVE

• ? To identify prognostic indicators that influence post‐recurrence survival following radical cystectomy for bladder cancer.

PATIENTS AND METHODS

• ? In all, 2029 patients with bladder cancer underwent radical cystectomy with intent to cure between 1971 and 2005 at our institution. Of these, 447 patients (22%) developed non‐urinary tract recurrence and were chosen for further analysis.
• ? Clinicopathological characteristics were analysed by univariate and multivariate analysis to identify factors prognostic for post‐recurrence survival.

RESULTS

• ? Median time to recurrence was 13.21 months and median post‐recurrence overall survival was 5.59 months.
• ? Pathological stage (P < 0.001), intravesical therapy (P= 0.035), tumour upstaging (P < 0.001), lymph node density (P < 0.001) and recurrence site (P= 0.017) were associated with time to recurrence.
• ? Age (P= 0.042), type of urinary diversion (P < 0.014), surgical margin status (P= 0.049), pathological stage (P < 0.001), lymph node density (P < 0.001), time to recurrence (P < 0.001), recurrence site (P < 0.001) and post‐recurrence chemotherapy administration (P < 0.001) were univariately prognostic for post‐recurrence overall survival.
• ? Multivariate analysis confirmed the associations of pathological stage, type of urinary diversion, lymph node density, time to recurrence after cystectomy, site of recurrence and post‐recurrence chemotherapy administration with outcome following bladder cancer recurrence.
• ? Median post‐recurrence survival with either local or distant recurrence was 7.95 months and 5.95 months, respectively, whereas patients with both local and distant recurrences had median post‐recurrence survival of 3.98 months.

CONCLUSIONS

• ? Bladder cancer recurrence forebodes poor prognosis, with 6 months' median survival following recurrence. Advanced pathological stage, positive surgical margins, high lymph node density and early recurrence portends poorer outcome.
• ? Although patients with local recurrence have a slightly better prognosis, those with disease recurrence at local and distant sites perform very poorly; nearly 97% of all patients with recurrence eventually succumb to the disease.
• ? Chemotherapy administration following recurrence may improve survival, although further studies are needed to exclude selection bias.

     

Comparison of oncological outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for the management of clear‐cell renal cell carcinoma: a multi‐institutional study

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic radical nephrectomy (LRN) can be performed by a retroperitoneal approach with similar efficacy compared to the transperitoneal approach. However, the oncological acceptance of LRN has been based on studies which have been carried out primarily by transperitoneal approach, and oncological results of the retroperitoneal approach alone are lacking. Our study confirmed that retroperitoneal laparoscopic radical nephrectomy is oncologically‐equivalent to transperitoneal approach in homogeneous group with the final pathological diagnosis of clear cell RCC.

OBJECTIVE

• ? To investigate the oncological efficacy of retroperitoneal laparoscopic radical nephrectomy (RLRN) compared with transperitoneal laparoscopic radical nephrectomy (TLRN) for the management of clear‐cell renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? With emphasis on survival and disease recurrence, a retrospective analysis was made of 580 patients who underwent TLRN (472 patients) or RLRN (108 patients) at 23 institutions between January 1997 and December 2007.
• ? Inclusion criteria were clear‐cell RCC, stage pT1 to pT2 without any nodal involvement, and metastasis.
• ? Overall survival and recurrence‐free survival curves were estimated using the Kaplan–Meier method.
• ? To assess the association between the surgical approach and survival outcomes, Cox proportional hazard models were constructed.

RESULTS

• ? The median follow‐up was 30 months in the TLRN group and 35.6 months in the RLRN group. Both groups were comparable regarding age, gender, body mass index (BMI), Fuhrman’s grade, size of tumours and stage.
• ? Kaplan–Meier curves and the log‐rank test showed no significant difference between the TLRN and RLRN groups in 5‐year overall (92.6% vs 94.5%; P = 0.669) and recurrence‐free survival (92.0% vs 96.2%; P = 0.244).
• ? In a Cox regression model with age, gender, Eastern Cooperative Oncology Group performance status, BMI, nuclear grade and T‐stage adjusted variables, no significant difference was found between the two surgical approaches.

CONCLUSION

• ? The present study is the largest oncological analysis for laparoscopic radical nephrectomy (LRN) comparing transperitoneal and retroperitoneal approaches. The data from it provide the objective evidence to suggest similar oncological outcomes for both approaches to LRN.

     

Comparison of the rate, location and size of positive surgical margins after laparoscopic and robot-assisted laparoscopic radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To review and compare the rate, location and size of positive surgical margins (PSMs) after pure laparoscopic radical prostatectomy (LRP) and robot‐assisted laparoscopic radical prostatectomy (RALP).

PATIENTS AND METHODS

• ? The study comprised 200 patients who underwent RALP and 200 patients who underwent LRP up to January 2008.
• ? We compared patient age, body mass index, preoperative prostate‐specific antigen (PSA), preoperative stage and grade, prostate size, pathological stage and grade and neurovascular bundle preservation, as well as PSM rate, size and location.
• ? Continuous and categorical data were compared using Student’s t‐test and Pearson’s chi‐squared test.
• ? Multivariate regression analyses were used to identify preoperative and intraoperative predictors of PSMs.

RESULTS

• ? Although the PSM rate was similar between the two groups (LRP: 12% vs RALP: 13.5%; P= 0.76), location and size were not. PSMs after LRP were mostly at the apex (58.3%; P= 0.038), while most PSMs after RALP were posterolateral ([PL] 48%; P= 0.046).
• ? In addition, the median margin size after RALP was significantly smaller than after LRP (RALP: 2 mm vs LRP: 3.5 mm; P= 0.041).
• ? In univariate and multivariate analyses, tumour‐node‐metastasis (TNM) stage and preoperative PSA were the only independent preoperative predictors of PSMs (P= 0.044 and P= 0.01, respectively).

CONCLUSION

• ? The PSM risk is dependent on TNM stage and preoperative PSA and not the surgical technique, when comparing LRP with RALP.

     

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high‐grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low‐ and intermediate‐risk features; there is a paucity of data about preoperative criteria to identify men with high‐grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high‐grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high‐grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate‐specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high‐grade prostate cancer as to their risk of favourable or unfavourable disease at RP.

OBJECTIVE

• ? To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8–10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).

PATIENTS AND METHODS

• ? The Institutional Review Board‐approved institutional RP database (1982–2010) was analysed for men with high‐Gleason prostate cancer on biopsy; 842 men were identified.
• ? The 10‐year biochemical‐free (BFS), metastasis‐free (MFS) and prostate cancer‐specific survival (CSS) were calculated using the Kaplan–Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8–10 and pT3b or N1.
• ? Preoperative characteristics were compared using appropriate comparative tests.
• ? Logistic regression determined preoperative predictors of unfavourable pathology.

RESULTS

• ? There was favourable pathology in 656 (77.9%) men. The 10‐year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively.
• ? In contrast, men with unfavourable pathological findings had significantly worse 10‐year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001).
• ? In multivariable logistic regression, a prostate‐specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38–3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55–4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59–4.09, P < 0.001), increasing number of cores positive with high‐grade cancer (OR 1.16, 95% CI 1.01–1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17–4.35, P= 0.015) were predictive of unfavourable pathology.

CONCLUSIONS

• ? Men with high‐Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis.
• ? Among men with high‐Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high‐grade cancer and >50% core involvement are predictive of unfavourable pathology.

     

Combined p53 and MDM2 biomarker analysis shows a unique pattern of expression associated with poor prognosis in patients with renal cell carcinoma undergoing radical nephrectomy

What's known on the subject? and What does the study add? Unlike most other cancers mutations of the p53 gene (TP53), typically indicated by increased p53 expression, are rare in renal cell carcinomas (RCC) and there is no evidence that mutation of TP53 is associated with outcome or treatment response. However, whilst TP53 mutations are not linked with outcome, p53 expression is as we show here. Our study is the first to demonstrate simultaneously that patients with increased p53 expression (significantly associated with MDM2 expression), have reduced disease specific survival even though the expressed p53 is rarely mutated. We therefore identify increased expression of wild‐type p53 and MDM2 in RCC as targets for future therapeutic approaches.

OBJECTIVE

• ? To resolve much debated issues surrounding p53 function, expression and mutation in renal cell carcinoma (RCC), we performed the first study to simultaneously determine p53/MDM2 expression, TP53 mutational status (in p53‐positive patients) and outcome in RCC.

PATIENTS AND METHODS

• ? In total, 90 specimens obtained from patients with RCC, who were treated by radical nephrectomy, were analyzed by immunohistochemistry for p53 and MDM2 on a tissue microarray, and p53 was functionally and genetically analyzed in p53 positive samples.
• ? Outcome analysis was by the Kaplan–Meier method and univariate analysis was used to identify variables for subsequent multivariate analysis of correlations between clinical parameters and biomarker expression.

RESULTS

• ? Up‐regulation of p53 in RCC is strongly linked with MDM2 up‐regulation (P < 0.001).
• ? Increased coexpression of p53 and MDM2 identifies those patients with a significantly reduced disease‐specific survival by univariate (P= 0.036) and Cox multiple regression analysis (P= 0.027; relative risk, 3.20).
• ? Functional (i.e. functional analysis of separated alleles in yeast) and genetic analysis of tumours with increased p53 expression shows that most patients (86%) retain wild‐type p53.

CONCLUSIONS

• ? Coexpression of p53/MDM2 identifies a subset of patients with poor prognosis, despite all of them having organ‐confined disease.
• ? Up‐regulated p53 is typically wild‐type and thus provides a mechanistic explanation for the association between p53 and MDM2 expression: up‐regulated wild‐type p53 likely promotes the observed MDM2 coexpression.
• ? The results obtained in the present study suggest that the p53 pathway is altered in a tissue/disease‐specific manner and that therapeutic strategies targeting this pathway should be investigated to determine whether the tumour suppressive function of p53 can be rescued in RCC.