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.

     

Evans blue as a selective dye marker for white-light diagnosis of non-muscle-invasive bladder cancer: an in vitro study

What's known on the subject? and What does the study add? We found that Evans blue preferentially accumulate in spheroids prepared from urothelial cell carcinoma (UCC) cells as compared to spheroids composed of normal human urothelial (NHU) cells. The present findings could be important for future developments in clinical diagnostics for early bladder cancer detection staging and grading involving white light cystocopy.

OBJECTIVE

• ? To develop a diagnostic method relying on the preferential accumulation of a dye in non‐muscle‐invasive bladder cancer (NMIBC) that is visible in conjunction with white‐light cystoscopy (WLC).

MATERIALS AND METHODS

• ? We investigated in detail the permeation of Evans blue in urothelial cell carcinoma (UCC) spheroids prepared from T24, J82 and RT‐112 human cell lines and spheroids composed of normal human urothelial (NHU) cells.
• ? To gain more insight into the differential accumulation, all spheroids were investigated ultrastructurally using transmission electron microscopy (TEM).

RESULTS

• ? We found that, after exposure to Evans blue for 2 h, UCC spheroids accumulated dramatically more dye than spheroids composed of NHU cells.
• ? Using TEM it was found that the malignant spheroids contain similar ultrastructural characteristics, i.e. a wide intercellular space and a decreased number of desmosome‐like cell attachments, to those from clinical samples of non‐papillary carcinoma in situ of the bladder.

CONCLUSION

• ? We believe the present findings could be important for future developments in clinical diagnostics for early bladder cancer detection, staging and grading involving WLC.

     

The use of estramustine phosphate in the modern management of advanced prostate cancer

What’s known on the subject? and What does the study add? Estramustine phosphate has anti‐tumour properties and it improves patient outcomes if combined with other chemotherapy agents such as doeetaxel. The efficacy of estramustine phosphate in selected patients and its safety profile, provided used with any low‐molecular‐weight heparin support its use as a second‐line treatment in hormone‐resistant prostate cancer.

OBJECTIVES

• ? Estramustine phosphate is a nitrogen mustard derivative of estradiol‐17β‐phosphate and has anti‐tumour properties.
• ? Interest in estramustine has been renewed because of the results of clinical studies showing improved patient outcomes if estramustine is combined with other chemotherapy agents such as docetaxel.

PATIENTS AND METHODS

• ? Relevant clinical studies using chemotherapy combinations including estramustine are discussed.
• ? Efficacy and safety outcomes are summarized.

RESULTS

• ? Combination therapy with estramustine and docetaxel can increase PSA response rates, improve quality of life and increase median patient survival compared with chemotherapy regimens that do not include estramustine.
• ? Although the overall tolerability of estramustine is favourable, its use can be associated with an increased risk of thromboembolic events.

CONCLUSIONS

• ? The identification of suitable patient groups and the effective management of the risk of thromboembolism with the adjunct of low‐molecular‐weight heparins support the use of estramustine as an effective second‐line treatment strategy in hormone‐resistant prostate cancer.
• ? These promising findings warrant further investigation in a randomized clinical trial.

     

Use of fluorescein isothiocyanate-human serum albumin for the intravesical photodiagnosis of non-muscle-invasive bladder cancer: an in vitro study using multicellular spheroids composed of normal human urothelial and urothelial cell carcinoma cell lines

OBJECTIVE

• ? To evaluate human serum albumin (HSA), fluorescently labelled with fluorescein isothiocyanate (FITC), as a potential intravesical photodiagnostic method for the early detection of non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

• ? By using multicellular spheroids prepared from normal human urothelial (NHU) cells and from different urothelial cell carcinoma (UCC) cell lines (T24, J82), we simulated three‐dimensionally the normal urothelium and non‐muscle‐invasive UCCs present in the bladder of patients.
• ? The distribution of FITC‐HSA in these spheroids was investigated.

RESULTS

• ? Our data showed that fluorescently labelled albumin is quite evenly dispersed throughout the spheroids. However, in the case of the 10 mg/mL incubations, the fluorescence intensity seems to increase slightly towards the spheroid core.
• ? Using 1 mg/mL, the penetration of FITC‐HSA in T24 differed significantly from the penetration in NHU spheroids, but this was not the case for J82 spheroids.
• ? When the concentration of FITC‐HSA was increased 10‐fold, all UCC spheroids exhibited a significantly different accumulation of FITC‐HSA.

CONCLUSIONS

• ? As spheroids represent a suitable in vitro model for predicting the in vivo behaviour of compounds, our data suggest that FITC‐HSA could be used for the early detection of non‐muscle‐invasive bladder cancer.
• ? Human serum albumin conjugates of new or already available intravesical drugs could be generated to create alternative bladder cancer therapies with increased selectivity.

     

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.

     

Targeting castration‐induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model

What’s known on the subject? and What does the study add? Castration therapy has rather modest effects on cell death in tumours but can be enhanced by other treatments targeting tumour stroma and vasculature. This study shows that the prostate becomes hypoxic following castration and that targeting hypoxic cells during castration therapy potently enhances the effects of castration.

OBJECTIVE

• ? To explore the effects of castration therapy, the standard treatment for advanced prostate cancer, in relation to tumour hypoxia and to elicit its importance for the short‐ and long‐term therapeutic response.

MATERIAL AND METHODS

• ? We used the androgen‐sensitive rat Dunning H prostate tumour model that transiently responds to castration treatment followed by a subsequent relapse, much like the scenario in human patients.
• ? Tumour tissues were analysed using stereological methods in intact, 1 and 7 days after castration therapy.

RESULTS

• ? Hypoxia was transiently up‐regulated after castration therapy and correlated with the induction of tumour cell apoptosis.
• ? When castration therapy was combined with tirapazamine (TPZ), a drug that targets hypoxic cells and the vasculature, the effects on tumour cell apoptosis and tumour volume were enhanced in comparison to either castration or TPZ alone.

CONCLUSION

• ? The present study suggests that castration‐induced tumour hypoxia is a novel target for therapy.

     

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.

     

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.

     

Immediate radical cystectomy vs conservative management for high grade cT1 bladder cancer: is there a survival difference?

Study Type – Aetiology (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? For patients with high grade (HG) non‐muscle invasive urothelial cell cancer (UCC) of the bladder, transurethral resection of bladder tumor (TURBT) in conjunction with induction and maintenance intravesical therapy is a commonly used treatment modality. Early cystectomy, although offering the best opportunity for cure, would in turn constitute overtreatment in some cases. Conservative management strategies, as opposed to radical surgery, are a viable treatment option within a well selected subset of patients with HG T1 UCC.

OBJECTIVE

• ? To determine whether a survival difference exists between patients with high grade (HG) cT1 urothelial cell carcinoma (UCC) receiving immediate radical cystectomy (IRC) as opposed to those choosing bladder‐sparing therapy.

PATIENTS AND METHODS

• ? Between January 1990 and August 2010, 349 patients were retrospectively identified with a diagnosis of HG cT1 UCC of the bladder. Patients were divided into two groups: those who underwent IRC and those treated with conservative management (CM), consisting of transurethral resection of the bladder tumour (TURBT) and intravesical therapy. IRC was defined as surgery within 90 days of HG cT1 diagnosis with no intervening transurethral resection (TUR) or intravesical therapy (IVT). Trends in patient selection and cancer‐specific survival (CSS) were analyzed over consecutive decades.
• ? The primary outcome was to compare CSS among patients during consecutive decades whereby management paradigms shifted from IRC to CM. The secondary outcome was to examine whether patient selection changed over time for each respective intervention.

RESULTS

• ? One hundred and thirteen patients underwent IRC and 236 had CM. From 1990 to 1999, only 90 patients were diagnosed with HG cT1 disease, and a majority of patients (n= 54) underwent IRC. From 2000 to 2010, only 23% (59/259) of the patients with HG cT1 underwent IRC. Despite 42.3% more patients successfully maintaining their bladder in the long‐term, no difference in 5 year bladder CSS was noted between decades (77% vs 80% consecutively, P= 0.566). A subset analysis of risk factors for bladder cancer progression/recurrence demonstrated more patients with lymphovascular invasion (LVI) on TUR underwent IRC in the current era (13/59 (22.0%) vs 13/200 (6.5%), P < 0.001). These findings remain to be validated in prospective work at other institutions.

CONCLUSION

• ? Conservative management strategies are a viable treatment option within a well selected subset of patients with HG cT1 UCC.

     

IL-23 gene therapy for mouse bladder tumour cell lines

OBJECTIVES

• ? To evaluate the antitumour effects of IL‐23 gene transfer into mouse bladder carcinoma (MBT2) cells.
• ? To investigate the mechanisms underlying the subsequent constitutive secrection of IL‐23 by the MBT2 cells

MATERIALS AND METHODS

• ? An expression vector containing IL‐23 gene was introduced into MBT2 cells by liposome‐mediated gene transfer, and secretion of IL‐23 was confirmed by ELISA.
• ? The in vivo antitumour effect of IL‐23‐secreting MBT2 cells (MBT2/IL‐23) was examined by injecting the cells into syngeneic C3H mice.
• ? A tumour vaccination study using mitomycin C (MMC)‐treated IL‐23‐secreting MBT2 cells was carried out, and the usefulness of in vivo CD25 depletion for an additional vaccine effect was also investigated.
• ? The mechanisms underlying the antitumour effects were investigated by antibody depletion of CD8 or CD4 T cells, or natural killer cells, and cells infiltrating the tumour sites in vivo were assessed using immunohistochemistry.

RESULTS

• ? Stable transformants transduced with MBT2/IL‐23 secreted IL‐23 into the culture supernatant.
• ? Genetically engineered IL‐23‐secreting MBT2 cells were rejected in syngeneic mice.
• ? MBT2/IL‐23‐vaccinated mice inhibited the tumour growth of parental MBT2 cells injected at a distant site and this vaccine effect was enhanced by combination with in vivo CD25 depletion by an antibody.
• ? The main effector cells for the direct antitumour effect of MBT2/IL‐23 were CD8 T cells, which was shown by in vivo depletion and immunohistochemical study.

CONCLUSIONS

• ? IL‐23‐secreting MBT2 cells were rejected in syngeneic mice by the activation of CD8 T cells.
• ? MMC‐treated MBT2/IL‐23 can have a tumour vaccine effect for parental MBT2 cells, and this effect was enhanced by combination with in vivo CD25 depletion.

     

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.

     

Laparoscopic high-intensity focused ultrasound for renal tumours: a proof of concept study

Study Type – Therapy (case series)
Level of Evidence What’s known on the subject? and What does the study add? Renal cancer is increasingly diagnosed when tumours are small and asymptomatic, during routine abdominal imaging. Whilst surgery is an effective and potentially curative option, it carries a significant risk of complications. Recent work suggests that thermally ablative therapies (RFA, cryotherapy, HIFU) may be suitable minimally invasive treatment options in selected patients. The success of extracorporeal HIFU has been limited by the abdominal wall and rib‐cage limiting energy delivery. For this study, a purpose‐built laparoscopic HIFU probe was designed to allow direct application of the transducer to the tumour surface, thus facilitating tumour destruction. Successful and accurate tumour destruction was demonstrated, paving the way for further clinical trials, subject to device modifications.

OBJECTIVE

• ? To test and establish clinical proof of concept for a laparoscopic high‐intensity focused ultrasound (HIFU) device that facilitates delivery of ultrasound by direct application of a probe to the tumour surface.

PATIENTS AND METHODS

• ? Twelve patients with renal tumours were treated with laparoscopic HIFU using a newly designed probe inserted via an 18‐mm laparoscopic port.
• ? HIFU treatment was targeted at a pre‐defined proportion of the tumour and immediate laparoscopic partial or radical nephrectomy was then performed.

RESULTS

• ? No tumour ablation was seen in the first five patients which made modifications in the treatment protocol necessary. After this, definite histological evidence of ablation was seen in the remaining seven patients.
• ? The ablated zones were within the targeted area in all patients and no intra‐lesional skipping was seen.
• ? Subcapsular skipping was seen at the probe–tumour interface in two patients with viable tumour cells seen at microscopy.
• ? One patient did not undergo surgical extirpation; subsequent biopsy revealed no viable tumour cells.
• ? There were no intraoperative or postoperative complications directly related to HIFU therapy and patients have reached a mean (range) follow‐up of 15 (8–24) months with no evidence of metastatic disease or late complications.

CONCLUSIONS

• ? Tumour ablation with laparoscopic HIFU is feasible.
• ? Homogenous ablation can be achieved with no vital tissue within the targeted zone.
• ? The technique is associated with low morbidity and may have a role in the definitive management of small tumours.

     

Laparoscopic partial nephrectomy for multiple tumours: feasibility and analysis of peri-operative outcomes

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic nephron‐sparing procedures have been increasingly utilized. However, in the presence of multiple tumours the procedure choice is usually shifted to radical nephrectomy. In view of favourable perioperative outcomes, the benefits of minimally‐invasive, nephron‐sparing surgery in experienced hands could be safely extended to patients presenting with multiple ipsilateral renal masses.

OBJECTIVE

• ? To describe our experience with laparoscopic partial nephrectomy (LPN) for multiple kidney tumours and compare the outcomes with LPN performed for single masses.

PATIENTS AND METHODS

• ? Retrospective analysis of medical records of patients undergoing LPN at our institution between 2005 and 2009 was performed.
• ? The cohort was divided in two groups based on tumour focality: group 1, LPN for a single tumour (n= 99) and group 2, LPN for multiple ipsilateral tumours (n= 12).
• ? The groups were compared with regards to demographic and peri‐operative variables.

RESULTS

• ? Demographic variables were not different between the groups. Median dominant tumour size was 3.1 cm (interquartile range [IQR] 2.4–4.0) and 4.0 cm (2.3–5.9) in groups 1 and 2, respectively.
• ? Median secondary tumour size in group 2 was 1.0 cm (1.0–1.8).
• ? Operative times were longer in group 2 compared with group 1 (220 vs 160 min, P= 0.009).
• ? Warm ischaemia times (WIT) (23 vs 22 min) and estimated blood loss (EBL) (100 vs 85 mL) were similar.

CONCLUSIONS

• ? LPN is a viable option for the treatment of multiple ipsilateral renal tumours.
• ? Peri‐operative outcomes are similar to standard LPN with the exception of longer operative time.
• ? In experienced hands, the advantages of minimally invasive surgery may be extended to select patients with ipsilateral multifocal renal tumours.

     

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995-2006

Study Type – Prevalence (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? In the UK, specialist services for the management of urological cancers have been reconfigured substantially in recent time periods. Socioeconomic inequalities in relative survival from bladder cancer have also been documented. In part of an English region, use of radical surgery to manage the most common type of bladder cancer increased and use of radiotherapy decreased during 1995–2006, most probably reflecting increasing availability of specialist surgical management. There was no evidence for differences in the use of radiotherapy or radical surgery between patients of different socio‐economic groups.

OBJECTIVE

• ? To examine the use of radiotherapy and radical surgery for bladder urothelial cell carcinoma (UCC) before, during and after national initiatives for reorganization of uro‐oncology services.

PATIENTS AND METHODS

• ? Population‐based data (1995–2006) from a cancer registry with stable coding practices were analysed.
• ? Bladder UCC was defined using relevant International Classification of Disease site and morphology codes.
• ? Time trends in the use of radiotherapy and radical surgery, and other predictors of their use were examined.

RESULTS

• ? Of 4639 bladder UCC patients aged ≥40 years (76% men), stage information was available for 4303 (93%).
• ? Morphology and stage case mix remained stable during the study period.
• ? Radiotherapy use decreased significantly (from 31% in 1995–1998 to 22% in 2003–2006, P < 0.001) among patients of any stage, whilst radical surgery use increased significantly (from 8 to 13%, P < 0.001), particularly among stage II–IV patients.
• ? The proportion of patients treated by both radiotherapy and surgery also decreased notably (from 4.0 to 1.1%).
• ? Women were significantly more likely to present in stages II–IV [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.06–1.40, P= 0.005], and less likely to be treated with radiotherapy (OR = 0.84, 95% CI: 0.72–0.99, P= 0.036).

CONCLUSIONS

• ? Use of radical surgery in UCC invading bladder muscle increased and use of radiotherapy decreased during the study period, most probably reflecting the increasing availability of specialist surgical management. Sociodemographic variation in treatment was limited to lower use of radiotherapy in women.
• ? Further research should encompass treatment timeliness and other aspects of care quality, as well as exploring potential differences in endoscopic treatments for disease not invading bladder muscle.

     

Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single-centre study

Study Type – Therapy (individual cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Tumour enucleation was demonstrated to be an oncologically safe conservative treatment for small renal masses in agreement with the EAU guidelines. Nevertheless, the theoretical increased risk of positive surgical margins and local recurrence, led some authors to hypothesize a possible key role of laser or diathermy ablation of the tumour bed to free the kidney parenchyma from any tumour cells that extended in the kidney parenchyma. Our pathological and clinical results showed that tumour enucleation with no ablation of the tumour bed (e.g. diathermy, argon beam or Nd‐YAG laser) can ensure negative surgical margins and it is not associated with an increased risk of local recurrence.

OBJECTIVE

• ? To prospectively evaluate the risk of positive surgical margins and local recurrence after blunt tumour enucleation (TE) with no ablation of the tumour bed.

PATIENTS AND METHODS

• ? Between 2005 and 2007, data were gathered prospectively from 201 consecutive patients who had open TE with no ablation of the tumour bed.
• ? Overall, 164 consecutive patients had TE for single sporadic renal cell carcinoma (RCC).
• ? All patients had an abdominal computed tomography (CT) at the last follow‐up visit.

RESULTS

• ? The pathological review showed that 70.2% of tumours were pT1a, 18.9% were pT1b, 1.8% were pT2 and 9.1% were pT3a.
• ? The mean (range, interquartile range) tumour greatest dimension was 3.5 (0.5–12.5, 2.4–4.1) cm.
• ? Although no deliberate attempt to resect normal parenchyma was performed, the pathological analysis showed the presence of a thin layer of parenchyma with a mean (range) thickness of 0.97 (0.31–1.60) mm, around the tumour. None of the patients had positive surgical margins.
• ? At a mean (median, range) follow up of 40 (38, 25–62) months, three (1.8%) patients had local recurrence, of whom one (0.6%) had a true local recurrence at the enucleation site detected 35 months after surgery, while two had kidney recurrence elsewhere associated with concurrent systemic metastases diagnosed 16 and 13 months after surgery.

CONCLUSIONS

• ? TE with no ablation of the tumour bed is a safe technique with a local recurrence rate of 0.6%.
• ? The histopathological analysis showed the presence of a minimal tumour‐free surgical margin, although no deliberate attempt to resect normal parenchyma is performed.

     

New drugs for prostate cancer

What's known on the subject? and What does the study add? Recent studies have demonstrated the efficacy of various new treatments. These have been in diverse areas of therapeutics research, including immunology and targeted biological therapy, as well as in new ways of approaching hormone refractory disease. The present paper seeks to review all of the key advances that have been reported in late‐stage clinical studies and place them into the context of managing patients with advanced prostate cancer.

OBJECTIVE

• ? To describe some of the most exciting late stage clinical developments in the field of new therapies for advanced prostate cancer.

METHODS

• ? Pubmed was searched for articles pertaining to prostate cancer therapeutics clinical trials in the last 3 years.

RESULTS

• ? Key positive trials in the areas of androgen resistance, tumour immunology, molecularly targeted agents and cytotoxics were reviewed and discussed in the context of metastatic prostate cancer.

CONCLUSION

• ? Treatments emerging from these areas of scientific endeavour are progressing into clinical trials and are both good cause for hope in patients, and excellent examples of mechanism based drug discovery.

     

Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carcinoma (RCC) in the USA: a propensity scoring approach

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Partial nephrectomy has become the standard of care for T1a renal tumours, and the application of nephron‐sparing techniques has increasingly been expanded to patients with localized T1b cancers. However, the relative efficacy of partial versus radical nephrectomy for these medium‐sized tumours has yet to be definitively established. This study employs a propensity scoring approach within a large US population‐based cohort to determine that no survival differences exist among patients with T1b renal tumours undergoing partial versus radical nephrectomy.

OBJECTIVES

• ? To compare survival after partial nephrectomy (PN) vs radical nephrectomy (RN) among patients with stage TIb renal cell carcinoma (RCC) using a propensity scoring approach.
• ? Propensity score analysis is a statistical methodology that controls for non‐random assignment of patients in observational studies.

PATIENTS AND METHODS

• ? Using the Surveillance, Epidemiology, and End Results registry, 11 256 cases of RCCs of 4–7 cm that underwent PN or RN between 1998 and 2007 were identified.
• ? Propensity score analysis was used to adjust for potential differences in baseline characteristics between patients in the two treatment groups.
• ? Overall survival (OS) and cancer‐specific survival (CSS) of patients undergoing PN vs RN was compared in stratified and adjusted analysis, controlling for propensity scores.

RESULTS

• ? In all, 1047 (9.3%) patients underwent PN. For the entire cohort, no difference in survival was found in patients treated with PN as compared with RN, as shown by the adjusted hazard ratio (HR) for OS (1.10; 95% confidence interval [CI]: 0.91–1.36) and renal‐CSS (HR 0.91; 95% CI: 0.65–1.27).
• ? When the cohort was stratified by tumour size and age, no difference in survival was identified between the groups.

CONCLUSIONS

• ? Even when stratified by tumour size and age, a survival difference between PN and RN in a propensity‐adjusted cohort of patients with T1b RCC could not be confirmed.
• ? If validated in prospective studies, PN may become the preferred treatment for T1b renal tumours in centres experienced with nephron‐sparing surgery.

     

Expression of the tumour antigen T21 is up-regulated in prostate cancer and is associated with tumour stage

What's known on the subject? and What does the study add? T21 is an immunogenic prostate‐associated tumor antigen identified by SEREX expression cloning and shown to have a highly restricted mRNA expression profile. This study shows the expression of T21 at the protein level in a panel of tissues and cell lines and demonstrates increasing levels of T21 protein expression in patients with more advanced stage prostate cancer.

OBJECTIVES

• ? To define the expression pattern of the tumour antigen T21 at the protein level in prostate tissues, prostate cell lines and a panel of normal tissues.
• ? To correlate the expression pattern of T21 in prostate cancer with clinical parameters.

PATIENTS AND METHODS

• ? Tissue samples were collected from 79 patients presenting at clinic with either prostate cancer (63 patients) or benign prostatic hyperplasia (BPH, 16 patients).
• ? A tissue microarray (TMA) was constructed from 44 of the prostate cancer tissues and areas of benign disease (43 patients) from these tissues were also included on the TMA. The remaining tissues (prostate cancer 19 patients and BPH 16 patients) were mounted fresh frozen onto cork boards and sectioned.
• ? Full ethical approval was granted for all aspects of the study and informed patient consent was taken before tissue collection.
• ? Immunohistochemistry was used on the prostate tumour TMA, the normal tissue TMA and the fresh‐frozen prostate tissues. Fluorescent microscopy and flow cytometry was performed on prostate cell lines.

RESULTS

• ? Expression of T21 was highly restricted within normal tissues with only the stomach, ovary, breast and prostate having detectable T21 expression.
• ? T21 was significantly over‐expressed in prostate cancer glands compared with benign tissue and was present in >80% of the malignant specimens analysed.
• ? Increased expression was positively correlated to pathological stage of prostate tumours.
• ? Additionally, T21 was associated with Gleason grade and prostate‐specific antigen recurrence, although statistical significance was not reached in this restricted cohort of patients.

CONCLUSION

• ? Taken together these results show that T21 is a potential new biomarker for advanced disease and that elevated levels of T21 appear relevant to prostate cancer development.

     

Delayed proximal ureteric stricture formation after complex partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? As the indications for nephron sparing surgery continue to evolve, so do the potential complications. This study examines a rare but likely underreported complication of nephron sparing surgery in order to better counsel and treat patients with complex renal tumours.

OBJECTIVE

• ? To report and review our incidence of delayed ureteric stricture (US) after complex nephron‐sparing surgery (NSS).

PATIENTS AND METHODS

• ? Using our institutional kidney cancer database, we identified 720 patients who underwent NSS from 1 January 2000 until 31 December 2010 and identified eleven (1.5%) patients with a delayed US.
• ? Patient and tumour characteristics were reviewed.

RESULTS

• ? Median (range) tumour size and RENAL nephrometry score was 4.1 (2–7.2) cm and 10p (4–11p), respectively.
• ? There were eight of 10 solitary tumours (80%) located in the lower or mid‐pole of the kidney.
• ? There were eight of 11 patients with delayed US (72.7%) who experienced a postoperative urinary leak.
• ? There were two of 11 (18.2%) patients who experienced a postoperative retroperitoneal haemorrhage, with one of these patients requiring selective embolization.
• ? All US were in the upper third of the ureter and were diagnosed at a minimum of 10 weeks postoperatively (median 154 days, range 70–400 days).

CONCLUSIONS

• ? US formation is an uncommon and under‐reported event after complex NSS.
• ? Risk factors appear to include tumour complexity, imperative indications, mid‐ or lower pole location, postoperative urinary leak and haemorrhage.
• ? Although uncommon, postoperative US can occur after NSS for complex renal masses, necessitating patient counselling and diligent postoperative surveillance.

     

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.