Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? In patients treated with radical cystectomy, pelvic lymph node dissection may have a beneficial effect on cancer control outcomes. We examined the effect of pelvic lymph node dissection on stage‐specific cancer control outcomes.

OBJECTIVE

• ? To examine the effect of stage‐specific pelvic lymph node dissection (PLND) on cancer‐specific (CSM) and overall mortality (OM) rates at radical cystectomy (RC) for bladder cancer.

METHODS

• ? Overall, 11 183 patients were treated with RC within the Surveillance, Epidemiology, and End Results database.
• ? Univariable and multivariable Cox regression analyses tested the effect of PLND on CSM and OM rates, after stratifying according to pathological tumour stage.

RESULTS

• ? Overall, PLND was omitted in 25% of patients, and in 50, 35, 27, 16 and 23% of patients with respectively pTa/is, pT1, pT2, pT3 and pT4 disease (P < 0.001).
• ? For the same stages, the 10‐year CSM‐free rates for patients undergoing PLND compared with those with no PLND were, respectively, 80 vs 71.9% (P = 0.02), 81.7 vs 70.0% (P < 0.001), 71.5 vs 56.1% (P = 0.001), 43.7 vs 38.8% (P = 0.006), and 35.1 vs 32.0% (P = 0.1).
• ? In multivariable analyses, PLND omission was associated with a higher CSM in patients with pTa/is, pT1 and pT2 disease (all P ≤ 0.01), but failed to achieve independent predictor status in patients with pT3 and pT4 disease (both P ≥ 0.05).
• ? Omitting PLND predisposed to a higher OM across all tumour stages (all P ≤ 0.03).

CONCLUSIONS

• ? Our results indicate that PLND was more frequently omitted in patients with organ‐confined disease.
• ? The beneficial effect of PLND on cancer control outcomes was more evident in these patients than in those with pT3 or pT4 disease.
• ? PLND at RC should always be considered, regardless of tumour stage.

     

Risk group stratification to predict recurrence after transurethral resection in Japanese patients with stage Ta and T1 bladder tumours: validation study on the European Association of Urology guidelines

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? EAU guidelines on non‐muscle‐invasive bladder tumours have been widely used for the prediction of recurrence after TUR. However, there are substantial differences in bladder cancer incidence and mortality rates between European countries and Japan. This study provides useful factors for predicting recurrence and validation of EAU guidelines on the risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.

OBJECTIVE

• ? To validate the European Association of Urology (EAU) guidelines on risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.

PATIENTS AND METHODS

• ? A cohort of 592 Japanese patients who were treated with transurethral resection (TUR) and histopathologically diagnosed with Ta and T1 urothelial carcinoma of the bladder were enrolled in this retrospective study.
• ? The primary endpoint of the present study was recurrence‐free survival, and the median follow‐up duration was 37 months in recurrence‐free survivors.

RESULTS

• ? Multivariate Cox proportional hazards regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), prior recurrence rate, number of tumours and T category were independent predictors of time to recurrence (P < 0.05). According to the EAU guidelines for predicting recurrence, the vast majority of Japanese patients were classified into intermediate risk.
• ? The intermediate‐risk patients were further divided into intermediate‐low‐risk and intermediate‐high‐risk subgroups based on the European Organization for Research and Treatment of Cancer risk table, and a significant difference in the recurrence‐free survival rates was found between these subgroups (P < 0.001).
• ? It was also found that patients with high risk combined with intermediate‐high risk had significantly poorer recurrence‐free survival rates than those with low risk combined with intermediate‐low risk (P < 0.001).

CONCLUSIONS

• ? This is the first report on the ECOG PS as a potentially useful predictor for bladder tumour recurrence.
• ? The risk group stratification of the EAU guidelines for recurrence might not be applicable to Japanese patients with Ta and T1 bladder tumours, but the subgroup classification of intermediate risk could be appropriate.

     

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population‐based study

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Given the natural history of pT4 urothelial carcinoma of the urinary bladder, and the substantially poorer survival of pT4 patients relative to pT3, it may be argued that radical cystectomy is not justified in these patients. Relying on a large population‐based retrospective analysis, the current study identified two main categories of patients with pT4 urothelial carcinoma of the urinary bladder. The first comprised of patients with pT4b disease, whose disease phenotype was clearly more aggressive than their pT3 counterparts. The second group consisted of patients with pT4a disease, whose disease phenotype was very similar to patients with pT3. These findings indicate that patients with pT4b disease should be provided with the maximal amount of therapeutic interventions, such as administration of early adjuvant chemotherapy and perhaps early adjuvant radiotherapy.

OBJECTIVE

• ? To examine cancer‐specific mortality (CSM) in patients with pT4N_0–3M₀ urothelial carcinoma of the urinary bladder (UCUB) and to compare it to patients with pT3N_0–3M₀, in a population‐based cohort treated with radical cystectomy (RC).

PATIENTS AND METHODS

• ? RCs were performed in 5625 pT3‐T4bN_0–3M₀ patients with UCUB within 17 Surveillance, Epidemiology and End Results (SEER) registries between 1988 and 2006.
• ? Univariable and multivariable models tested the effect of pT4a vs pT4b vs pT3 stages on CSM.
• ? Covariates consisted of age, gender, race, lymph node status and SEER registries.
• ? All analyses were repeated in 3635 pN₀ patients.

RESULTS

• ? Of 5625 patients, 2043 (36.3%) had pT4aN_0–3, 248 (4.4%) had pT4bN_0–3 and 3334 had pT3N_0–3 (59.3%) UCUB.
• ? The 5‐year CSM was 57.6% vs 81.7% vs 53.9% for, respectively, pT4aN_0–3 vs pT4bN_0–3 vs pT3N_0–3 patients (all log‐rank P= 0.008).
• ? In multivariable analyses the rate of CSM was 2.3‐fold higher in pT4b vs pT3 (P < 0.001), 1.1‐fold higher in pT4a vs pT3 (P= 0.002) and 2.0‐fold higher in pT4a vs pT4b patients.
• ? After restriction to pN₀ stage, pT4b patients had a 2.3‐fold higher rate of CSM than pT3 patients (P < 0.001) and pT4b patients had a 2.1‐fold higher rate of CSM than pT4a patients (P < 0.001).
• ? The CSM rate was the same for pT4a and pT3 patients (P= 0.1).

CONCLUSIONS

• ? Our findings indicate that patients with pT4a UCUB have similar CSM as those with pT3 UCUB.
• ? Consequently, RC should be given equal consideration in patients with pT3 and pT4a UCUB.

     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

International validation of the prognostic value of subclassification for AJCC stage pT3 upper tract urothelial carcinoma of the renal pelvis

Study Type – Prognosis (inception cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Tumour stage is a powerful predictor of clinical outcomes and the most important factor driving clinical decision‐making after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). It has been suggested that renal pelvic pT3 subclassification into microscopic infiltration of the renal parenchyma (pT3a) versus macroscopic infiltration or invasion of peripelvic adipose tissue (pT3b) has strong prognostic value. This is an external validation study of the prognostic value of pT3 subclassification of renal pelvic UTUC in a large international cohort of patients treated with RNU. pT3b UTUC is associated with features of aggressive tumour biology, disease recurrence and cancer‐specific mortality. However, pT3 subclassification is not an independent predictor of clinical outcomes.

OBJECTIVE

• ? To externally validate the prognostic value of subclassification of pT3 renal pelvic upper tract urothelial carcinoma (UTUC) in a large international cohort of patients treated with radical nephroureterectomy (RNU).

PATIENTS AND METHODS

• ? The RNU specimens with pT3 UTUC of the renal pelvis from 284 patients at 11 centres located in Asia, North America and Europe were retrospectively evaluated. All specimens were reviewed by genitourinary pathologists at each institution. Tumours were categorized as pT3a (microscopic infiltration of the renal parenchyma) or pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

RESULTS

• ? Overall, 148 (52%) tumours were classified as pT3a and 136 (48%) as pT3b. Patients with pT3b disease were more likely to have high‐grade tumours and sessile tumour architecture (all P≤ 0.02). Patients with pT3b tumours were at increased risk of disease recurrence (5‐year estimates: 55% versus 42%, P= 0.012) and cancer‐specific mortality (CSM) (5‐year estimates: 48% versus 40%, P= 0.04). Lymph node status, tumour architecture and tumour grade were independently associated with disease recurrence, whereas lymph node status, tumour architecture and lymphovascular invasion were independently associated with CSM. Subclassification of pT3 tumours was not associated with recurrence or CSM in multivariable analyses.

CONCLUSION

• ? Patients with pT3b UTUC were more likely to have tumours with aggressive pathological features and were at higher risk of disease recurrence and CSM after RNU compared with patients with pT3a disease. However, the pT3 subclassification did not remain an independent predictor of disease recurrence or CSM after controlling for tumour grade, lymph node status, tumour architecture and lymphovascular invasion.

     

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.

     

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.

     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases

Study Type – Diagnostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC. The present study highlights the inaccuracy of biopsy in the setting of metastatic disease, which is related to sampling error because of heterogeneity within the tumour and among metastases. These limitations are important to realize when designing trials that depend on pathological findings from biopsy and not nephrectomy. In addition, we found that biopsy of primary tumours were more likely than biopsy of metastatic sites to be diagnostic of RCC. Future studies with multiquadrant biopsies of primary tumours could yield the most accurate pathological results for future studies.

OBJECTIVE

• ? To evaluate the ability of preoperative biopsy to identify high‐risk pathological features by comparing pathology from preoperative metastatic site and primary tumour biopsies with nephrectomy pathology in patients with metastatic renal cell carcinoma (mRCC).

PATIENTS AND METHODS

• ? We reviewed clinical and pathological data from patients who underwent biopsy before cytoreductive nephrectomy for mRCC at MD Anderson Cancer Center (MDACC) from 1991 to 2007.
• ? Percutaneous biopsy techniques included fine‐needle aspiration, core needle biopsy or a combination of both techniques.

RESULTS

• ? The pathology of 405 preoperative biopsies (239 metastatic site, 166 primary tumour) from 378 patients was reviewed at MDACC before cytoreductive nephrectomy.
• ? The biopsy and nephrectomy specimens had the same histological subtype in 96.0% of clear‐cell renal cell carcinomas (RCCs) and 72.7% of non‐clear‐cell RCCs.
• ? Of 76 nephrectomy specimens where sarcomatoid de‐differentiation was identified, only seven (9.2%) were able to be identified from the preoperative biopsy.
• ? In 38.3% of patients, the same Fuhrman grade was identified in both the biopsy and nephrectomy specimens.
• ? A definitive diagnosis of RCC was more likely to be reported in primary tumour biopsies than in metastatic site biopsies. (P < 0.001).

CONCLUSIONS

• ? Preoperative biopsy has limited ability to identify non‐clear‐cell histological subtype, Fuhrman grade or sarcomatoid features.
• ? When surgical pathology is not available, a biopsy obtaining multiple samples from different sites within the primary tumour should be recommended rather than limited metastatic site biopsy to identify patients for clinical trials.

     

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.

     

De novo renal cell carcinoma of native and graft kidneys in renal transplant recipients

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Immmunosuppression is an etablished risk factor for development of different maligancies. Nevertheless, little is known about the behaviour of renal cell cancer of native and graft kidneys in renal transplanted patients. The study results show an increased incidence of renal cell carcinoma in renal transplant recipients with high prevalence of papillary subtype, significantly younger patient age at the immunosuppression onset, aggressive behaviour with an increased tendency to systemic advance despite a high rate of low‐stage and low‐grade carcinomas at diagnosis. Furthermore, graft tumours had a more favourable prognosis than those of native kidney.

OBJECTIVE

• ? To access the epidemiological, clinical and survival features of renal transplant patients with de novo renal cell carcinoma of native and graft kidneys.

PATIENTS AND METHODS

• ? We performed a retrospective examination of the data of 2001 consecutive renal transplant recipients at our centre between November 1979 and January 2010.

RESULTS

• ? In the patient cohort examined, 30 renal cell carcinomas were observed in 26 individuals (incidence 1.5%) with 25 tumours in the native and five in allograft kidneys. Mean tumour size in surgical specimens was 44 ± 36 mm. The rate of papillary cancer was 37.5%.
• ? After a mean follow‐up of 58.6 ± 62.3 months, 15.4% of the patients died from cancer and 57.7% were in complete remission.
• ? Overall and tumour‐specific survival rates at 1, 5 and 10 years were 86.1%, 75.1% and 43.8%, and 90.4%, 83.5% and 66.8%, respectively.

CONCLUSIONS

• ? Due to increasingly improved survival after renal transplantation, de novo malignancies might soon become the main cause of intermediate‐ or long‐term mortality.
• ? Current data support an increased risk of renal cell carcinoma in renal transplant recipients in a particularly aggressive way, but low tendency for metachronous contralateral evolution.
• ? With continuous radiological follow‐ups, acceptable oncological outcome can be achieved. Graft tumours may have a favourable prognosis.

     

Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS‐guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole‐gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade.

OBJECTIVE

• ? To evaluate the ability of transrectal ultrasonography (TRUS)‐guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer.

PATIENTS AND METHODS

• ? Patients with early stage, low‐risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified.
• ? Re‐review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV).
• ? Pathology findings were then compared with biopsy results.

RESULTS

• ? A total of 51 men with early stage, low‐risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading.
• ? Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies.
• ? Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5–0.6) of specimens and the highest grade in 37% (95 CI 0.3–0.5).
• ? No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken and total length of tumour identified were significantly associated with correct identification of DV.

CONCLUSIONS

• ? Our findings show that TRUS‐guided biopsy detects and localizes DV better than it does DG.
• ? Even with an extended scheme, TRUS‐guided biopsy does not reliably identify dominant cancer location in this low‐risk cohort of men with early stage prostate cancer.
• ? TRUS‐guided biopsy may perform better in similar men with low stage, but higher volume disease.

     

Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In an array of urological and non‐urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20‐year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI‐positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI‐positive disease have overall survival outcomes similar to those of patients with muscle‐invasive LVI‐negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC.

OBJECTIVE

• ? To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

PATIENTS AND METHODS

• ? The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified.
• ? These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log‐rank tests and Cox proportional hazards regression models.
• ? Actuarial survival curves were calculated using the Kaplan–Meier method.

RESULTS

• ? LVI was observed in 68 patients (32.2%).
• ? The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5‐ and 10‐year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively.
• ? In multivariate analysis, age, race and LVI were independent predictors of overall survival.

CONCLUSIONS

• ? The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC.
• ? LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options.
• ? With confirmation from large international studies, inclusion of LVI in the tumour‐node‐metastasis staging system for UTUC should be considered.

     

Potential role of photodynamic techniques combined with new generation flexible ureterorenoscopes and molecular markers for the management of urothelial carcinoma of the upper urinary tract

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sporadic clear cell Renal Cell Carcinoma (ccRCC) is dominated by mutations of the VHL gene located on chromosome 3p in up to 90% of cases. This gene plays a critical role in hypoxia response, including stimulation of neoangiogenesis. Since 2006, anti‐angiogenic therapies targeting this pathway are used in metastatic patients with objective response rate as high as 45%. However, these treatments don't target directly the tumour cell, allowing the potential for disease progression despite treatment. Large scale analysis recently showed that substantial genetic heterogeneity exists in ccRCC. Associated alterations include genes implicated in methylation regulation in 15% of cases, underlying the importance of epigenetic modifications, and truncating mutations in chromatin remodeling complex PRMB1 in 41% of cases. Systematic screening of these tumours is a way to fully determine the somatic genetic architecture of RCC in order to improve tumour classification, to develop prognostic and predictive markers and to target new molecular pathways involved in carcinogenesis.

OBJECTIVES

• ? To discuss how the development of new generation flexible ureterorenoscopes in combination with photodynamic diagnosis (PDD) improves the assessment of urothelial cell carcinoma of the upper urinary tract (UUT‐UCC).
• ? Ultimately, this may allow accurate tumour classification and the ability to select which patients would benefit from conservative treatment as opposed to radical surgery.

MATERIALS AND METHODS

• ? We conducted an exhaustive Pubmed literature search using a combination of keywords including: ureterorenoscopy, UUT‐UCC diagnosis, PDD, narrow band imaging, conservative treatment UUT‐UCC and molecular urinalysis.
• ? We then selected salient high calibre articles relevant to our objective.

RESULTS

• ? We give specific consideration to anatomical aspects of UUT‐UCC investigation, PDD in UCC, aminolevulinic acid and its derivatives, autofluorescence, narrow band imaging, molecular marker analysis and the recent advances in ureterorenoscopic technology.
• ? The traditional pitfalls of UUT‐UCC diagnosis, namely poor visualisation and difficulty in obtaining representative histological samples, are being circumvented by the introduction of modern digital flexible ureteroscopes that can be combined with PDD and molecular analysis to improve tumour classification, deferring to conservative treatment accordingly.

CONCLUSION

• ? The accuracy of the diagnostic work‐up of UUT‐UCC is improving due to advances in technology, pharmaceutical agents and incorporation of molecular markers, all factors allowing us to characterise tumours of the UUT more definitively.

     

Percutaneous vs surgical cryoablation of the small renal mass: is efficacy compromised?

Study Type – Therapy (systematic review)
Level of Evidence 1b What’s known on the subject? and What does the study add? Cryoablation of the small renal mass is one amongst many minimally invasive approaches to treatment. Cryoablation can be performed both surgically and percutaneously; direct comparison of the two approaches has proven the percutaneous approach to be cheaper, less morbid, result in shorter procedure times, and shorter hospital stays, all with equal efficacy. Our study examines the decision as well as reporting process for the selection of treatment approach to determine if patients are being unnecessarily exposed to more invasive therapeutic options.

OBJECTIVE

• ? To review and analyse the cumulative literature to compare surgical and percutaneous cryoablation of small renal masses (SRMs).

METHODS

• ? A MEDLINE search was performed (1966 to February 2010) of the published literature in which cryoablation was used as therapy for localized renal masses.
• ? Residual disease was defined as persistent enhancement on the first post‐ablation imaging study, while recurrent disease was defined as enhancement after an initially negative postoperative imaging study, consistent with the consensus definition by the Working Group on Image‐Guided Tumor Ablation.
• ? Data were collated and analysed using the two‐sample Mann–Whitney test and random‐effects Poisson regression, where appropriate.

RESULTS

• ? In all, 42 studies, representing 1447 lesions treated by surgical (n= 28) or percutaneous (n= 14) cryoablation were pooled and analysed.
• ? No significant differences were detected between approaches regarding patient age (median 67 vs 66 years, P= 0.55), tumour size (median 2.6 vs 2.7 cm, P= 0.24),or duration of follow‐up (median 14.9 vs 13.3 months, P= 0.40).
• ? Differences in rates of unknown pathology also failed to reach statistical significance (14 vs 21%, P= 0.76). The difference in the rate of residual tumour was not statistically different (0.033 vs 0.046, P= 0.25), nor was the rate of recurrent tumour (0.008 vs 0.009, P= 0.44).
• ? The reported rate of metastases was negligible in both groups, precluding statistical analysis.

CONCLUSIONS

• ? Cryoablation has shown acceptable short‐term oncological results as a viable strategy for SRMs.
• ? Analysis of the cumulative literature to date shows that surgical and percutaneous cryoablation have similar oncological outcomes.

     

Early oncological outcomes for bladder urothelial carcinoma patients treated with robotic-assisted radical cystectomy

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

OBJECTIVE

• ? To determine oncological outcomes including early survival rates among unselected bladder urothelial carcinoma (BUC) patients treated with robotic‐assisted radical cystectomy (RRC).

PATIENTS AND METHODS

• ? Clinicopathologic and survival data were prospectively gathered for 85 consecutive BUC patients treated with RRC.
• ? The decision to undergo a robotic rather than open approach was made without regard to tumor volume or surgical candidacy.
• ? Kaplan–Meier survival rates were determined and stratified by tumor stage and LN positivity, and multivariate analysis was performed to identify independent predictors of survival.

RESULTS

• ? Patients were relatively old (25% >80 years; median 73.5 years), with frequent comorbidities (46% with ASA class ≥3). Of these patients 28% had undergone previous pelvic radiation or pelvic surgery, and 20% had received neoadjuvant chemotherapy.
• ? Extended pelvic lymphadenectomy was performed in 98% of patients, with on average 19.1 LN retrieved.
• ? On final pathology, extravesical disease was common (36.5%).
• ? Positive surgicalmargins were detected in five (6%) patients, all of whom had extravesical tumors with perineural and/or lymphovascular invasion, and most of whom were >80 years old.
• ? At a mean postoperative interval of 18 months, 20 (24%) patients had developed recurrent disease, but only three (4%) patients had recurrence locally. Disease‐free, cancer‐specific and overall survival rates at 2 years were 74%, 85% and 79%, respectively. Patients with low‐stage/LN(?) cancers had significantly better survival than extravesical/LN(?) or any‐stage/LN(+) patients, with stage being the most important predictor on multivariate analysis.

CONCLUSION

• ? RRC can achieve adequately high LN yields with a low positive margin rate among unselected BUC patients.
• ? Early survival outcomes are similar to those reported in contemporary open series, with an encouragingly low incidence of local recurrence, however long‐term follow‐up and head‐to‐head comparison with the open approach are still needed.

     

Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? While cytoreductive nephrectomy is associated with a survival benefit in the context of metastatic renal cell carcinoma, the rates of morbidity and perioperative mortality remain non‐negligible. For example, perioperative mortality may be as high as 21% in elderly patients. The study shows that perioperative death amongst the elderly was substantially lower than what was previously reported from a single institutional report. Nonetheless, postoperative adverse outcomes were non‐negligible in elderly patients relative to their younger counterparts. In consequence, these rates should be discussed at informed consent and a rigorous patient selection remains essential.

OBJECTIVE

• ? To examine the rate of perioperative mortality (PM), and other adverse outcomes in ‘elderly’ patients treated with cytoreductive nephrectomy (CNT).

MATERIAL AND METHODS

• ? Patients who underwent CNT for metastatic renal cell carcinoma were abstracted from the Nationwide Inpatient Sample (1998–2007). ‘Elderly’ was defined as ≥75 years, according to previous definition.
• ? Endpoints consisted of PM, intraoperative and postoperative complications, blood transfusions and length of stay.
• ? We adjusted for the effect of elderly status within five separate logistic regression models. Covariates consisted of comorbidity, race, gender, year of surgery and hospital region.

RESULTS

• ? Overall, CNT was performed in 504 (15.3%) elderly patients and in 2796 (84.7%) ‘younger’ patients (<75 years).
• ? The rate of PM was 4.8% in elderly patients vs 1.9% in the younger patients (P < 0.001). Similarly, the rates of blood transfusions (29.8 vs 21.5%), postoperative complications (27.8 vs 22.8%), and prolonged length of stay (≥8 days) were higher in the elderly (45.0 vs 32.0%; all P < 0.001).
• ? In multivariable analyses, elderly patients were 2.2‐, 1.5‐, and 1.6fold more likely to experience PM, to receive a blood transfusion and to be hospitalized ≥8 days than the younger patients.

CONCLUSIONS

• ? Although the rate of PM was substantially lower than 21%, elderly patients are significantly more likely to die after this type of surgery, to receive a transfusion, and to experience a prolonged length of stay.
• ? These facts and figures should be discussed at informed consent and a rigorous patient selection is essential.

     

Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long‐term follow‐up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic‐related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies.

OBJECTIVE

• ? To evaluate the association of cleaved caspase‐3 (CC‐3), Bax, COX‐2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder.

METHODS

• ? Immunohistochemistry for CC‐3, Bax, COX‐2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed.
• ? A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined.

RESULTS

• ? The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81%) patients.
• ? Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and lymphovascular invasion was found in 16% of patients.
• ? Median follow‐up was 63.2 months.
• ? Advanced stage was associated with COX‐2, p53 and CC‐3 alterations and high grade was associated with COX‐2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer‐specific mortality in Kaplan–Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95% confidence interval [CI] 1.386–5.235, P= 0. 003) and bladder cancer‐specific mortality (HR 2.868, 95% CI 1.209–6.802, P= 0. 017) in multivariable Cox regression analysis.

CONCLUSION

• ? Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.

     

Contrast-enhanced ultrasound using a time-intensity curve for the diagnosis of renal cell carcinoma

Study Type – Diagnosis (non‐consecutive series) Level of Evidence 3b What’s known on the subject? and What does the study add? In terms of imaging differentiation, distinguishing complex cystic renal masses that require surgery from those that do not remains a common and difficult diagnostic problem. Magnetic resonance imaging (MRI) is useful for characterizing complex cystic renal masses. But there are some cases that are difficult to diagnose differentially on computed tomography (CT) or MRI. We evaluated the usefulness of contrast‐enhanced ultrasound (CEUS) for the diagnosis of cystic renal cell carcinoma by using a time‐intensity curve (TIC). Assessments of blood flow in the solid component of a cystic tumour by CEUS using a second‐generation US contrast agent and TIC analysis have made it easier to objectively diagnose cystic renal cancer.

OBJECTIVE

• ? To evaluate the usefulness of contrast‐enhanced ultrasound (CEUS) for the diagnosis of renal cell carcinoma by employing a time‐intensity curve (TIC).

PATIENTS AND METHODS

• ? From May 2008 to October 2009, CEUS was performed prior to surgery in 30 patients with renal masses.
• ? In all, 10 of the 30 patients had cystic renal masses. The final diagnoses of all patients were pathologically confirmed. Contrast enhancement as a function of time was measured in two (tumour or solid component of cystic lesions and normal parenchyma) regions of interest (ROI) and TICs were obtained.
• ? The time to the contrast enhancement peak (TTP), intensity change from the baseline to peak (ΔI) and ΔI/TTP of the tumour and the normal parenchyma were measured from the TIC.

RESULTS

• ? Pathological diagnoses were renal cell carcinoma in 30 patients.
• ? The TTP of the cancer was shorter than that of the normal parenchyma in all cases (6.0 ± 2.0 vs 10.4 ± 3.0 s; P < 0.0001).
• ? The ΔI did not differ between the cancer and normal parenchyma [21.3 ± 5.9 vs 20.9 ± 7.0 decibels (db); P= 0.68]; the ΔI/TTP of the cancer was significantly higher than that of the normal parenchyma (3.9 ± 1.4 vs 2.2 ± 0.94 db/s; P < 0.0001).
• ? TIC patterns of solid cancer and cystic cancer were very similar.

CONCLUSIONS

• ? An objective and quantitative diagnosis of renal cell carcinoma by CEUS using a second‐generation ultrasound contrast agent can be made by employing a TIC.
• ? The TIC patterns of solid and cystic cancers were very similar, despite their morphological and vascular differences.
• ? CEUS using TIC is a promising tool in the diagnosis of cystic renal cancer.

     

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series

Study Type – Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non‐clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer‐specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer‐related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5‐ and 10‐year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence‐free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow‐up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer‐related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC.

OBJECTIVES

• ? To investigate cancer‐related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset.
• ? To determine prognostic factors for recurrence‐free survival (RFS) and cancer‐specific survival (CSS) for this RCC histological type.

PATIENTS AND METHODS

• ? In all, 291 patients with ChRCC were identified from a multi‐institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007.
• ? Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC.

RESULTS

• ? At a median follow‐up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease.
• ? The 5‐year RFS and CSS rates were 89.3% and 93%, respectively.
• ? Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis.
• ? For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables.

CONCLUSIONS

• ? Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer‐specific death.
• ? Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC.