Contrast-enhanced ultrasonography of the prostate: various imaging findings that indicate prostate cancer

Study Type – Diagnostic (non‐consecutive case series)
Level of Evidence 3b What’s known on the subject? and What does the study add? Contrast‐enhanced ultrasonography (CEUS) can visualize some prostate cancer lesions. Findings suggestive of cancer have been defined as rapid contrast enhancement; increased contrast enhancement. CEUS could be useful for targeted biopsy in patients with a PSA level <10 ng/mL. The CEUS findings suggestive of prostate cancer are more varied than previously reported. Low‐echogenicity areas containing abnormal blood vessels were also found to represent cancer.

OBJECTIVES

• ? To perform transrectal ultrasonography (TRUS) with an ultrasonography (US) contrast agent to visualize prostate cancer.
• ? To explore the possibility of targeted biopsy by studying the findings obtained by different cancerous tissue imaging modalities and evaluating needle biopsies from prostate cancer using contrast‐enhanced ultrasonography (CEUS).

PATIENTS AND METHODS

• ? In all, 41 patients undergoing prostate biopsy and 13 patients undergoing prostatectomy received i.v. injection of the US contrast agent (Sonazoid®).
• ? We evaluated pre‐contrast and contrast‐enhanced US images, and then compared ultrasonographic images and the pathological findings.

RESULTS

• ? Cancer was significantly more frequent at the sites of targeted biopsy where CEUS findings suggested cancer (36.3%) than at sites of systematic biopsy (17.7%, odds ratio = 2.7, P = 0.0026).
• ? In cases with prostate‐specific antigen (PSA) level <10 ng/mL, in particular, prostate cancer was detected at a significantly higher rate by targeted biopsy than by systematic biopsy (27.3 vs 9.5%, odds ratio = 3.4, P = 0.013).
• ? Pathological examination found 26 tumours in prostatectomy specimens. The diameters of the 10 CEUS‐identified tumours were significantly greater than those of the 16 lesions missed by US (mean 18.7 vs 5.9 mm).
• ? CEUS findings suggestive of cancer varied widely: strong contrast enhancement, rapid contrast enhancement, vessels with abnormal perfusion and low contrast enhancement.

CONCLUSIONS

• ? CEUS could be useful for targeted biopsy in patients with a PSA level <10 ng/mL.
• ? The CEUS findings suggestive of prostate cancer are more varied than previously reported.
• ? Detailed examination of CEUS images and application of the data to prostate biopsy could lead to more efficient diagnosis.

     

Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

• ? To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

• ? From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.
• ? The mean (median) follow‐up was 71 (68) months.
• ? Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

• ? The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).
• ? The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).
• ? The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.
• ? Gleason score was the only factor to significantly affect distant metastases.
• ? Grade ≥3 late toxicity was not detected.

CONCLUSION

• ? The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.

     

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.

     

Comparison of laparoscopic versus open radical nephrectomy for large renal tumors: a retrospective analysis of multi-center results

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? While laparoscopic radical nephrectomy (LRN) has been confirmed in various studies to be at least as efficacious as open radical nephrectomy (ORN) in terms of oncological control and more advantageous from the perspective of minimal invasiveness, very few studies have examined its feasibility and efficacy when applied to renal masses exceeding 7 cm in size, and even fewer involved results obtained from multicentre investigations. The present study retrospectively reviewed the outcome of LRN for masses exceeding 7 cm in size carried out in 26 institutions between 2000 and 2007 and concluded that LRN offers results comparable to ORN in terms of both tumour control and procedure‐associated morbidities. Furthermore, details from the study suggest that while the size of renal mass that can be treated using LRN may not be a necessarily limiting factor, the experience of the laparoscopic surgeon is a primary determinant in the overall outcome.

OBJECTIVE

• ? To assess the feasibility and oncologic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with large renal cell carcinomas (RCCs) >7 cm in size.

PATIENTS AND METHODS

• ? We analysed the data from 255 patients who underwent radical nephrectomies at 26 institutions in Korea between January 2000 and December 2007 for RCCs > 7 cm in size.
• ? Eighty‐eight patients who underwent LRNs were compared with 167 patients who underwent ORNs. The patients with tumor thrombi in the renal vein or IVC, and lymph node or distant metastases were excluded.
• ? We compared the operative time, estimated blood loss, complication rates, and 2‐year overall and disease‐free survival rates between the LRN and ORN groups.

RESULTS

• ? The median duration of postoperative follow‐up was 19 months for the LRN group and 25.8 months for the ORN group.
• ? The operative time was significantly longer in the LRN group than in the ORN group (241.5 ± 74.8 min vs 202.7 ± 69.6 min, P < 0.001) and blood loss was significantly lower in the LRN group than in the ORN group (439.8 ± 326.8 mL vs 604.4 ± 531.4 mL, P = 0.006).
• ? No statistically significant difference was found in complication rates, the 2‐year overall (92.7% vs 94%, P = 0.586) and disease‐specific (90.1% vs 93.7%, P = 0.314) survival rates between the LRN and ORN groups.

CONCLUSIONS

• ? Despite the longer operative time, LRN was an effective and less invasive treatment option for clinical T2 renal tumors. It achieved a degree of cancer control similar to that obtained with ORN.

     

Active surveillance of small renal masses offers short‐term oncological efficacy equivalent to radical and partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance of small renal masses has traditionally been reserved for elderly patients deemed unfit for surgery or ablation. There is increasing evidence showing the safety of active surveillance in the management of small renal masses. In this retrospective study we compared outcomes for patients with small renal masses managed with active surveillance, radical nephrectomy and partial nephrectomy. We showed that active surveillance was safe and appeared as effective as immediate surgery in the management of small renal tumours.

OBJECTIVE

• ? To compare the oncological outcomes of active surveillance (AS), radical nephrectomy (RN) and partial nephrectomy (PN) in the management of T1a small renal masses (SRMs).

PATIENTS AND METHODS

• ? At present AS is used in the treatment of SRMs in elderly patients with multiple co‐morbidities or in those who decline surgery.
• ? We identified all patients with T1a SRMs managed with RN, PN or AS.
• ? Retrospective data were collected from patient case records with survival data and cause of death cross‐referenced with the Oxford Cancer Intelligence Unit.

RESULTS

• ? A total of 202 patients with 234 T1a SRMs (solid or Bosniak IV) were identified; 71 patients were managed with AS, 41 with an RN and 90 by PN.
• ? Over a median follow‐up of 34 months the mean growth rate on AS was 0.21 cm/year with 53% of SRMs managed with AS showing negative or zero growth.
• ? No statistically significant difference was observed in overall (OS) and cancer‐specific (CSS) survival for AS, RN and PN (AS‐CSS 98.6%, AS‐OS 83%; RN‐CSS 92.6%, RN‐OS 80.4%; PN‐CSS 96.6%, PN‐OS 90.0%).

CONCLUSIONS

• ? Active surveillance of SRMs offers oncological efficacy equivalent to surgery in the short/intermediate term.
• ? The results of this study support a multicentre prospective randomized controlled trial designed to compare the oncological efficacy of AS and 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.

     

Contrast-enhanced ultrasonography with contrast-tuned imaging technology for the detection of prostate cancer: comparison with conventional ultrasonography

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The present study was to perform contrast‐tuned imaging (CnTI) technology to detect prostate cancer and compare the use of CnTI technology for the detection of prostate cancer with conventional ultrasonography. The preliminary data from our study suggested that targeted biopsy of the prostate with CnTI technology could improve the cancer detection and detect higher grade prostate cancers.

OBJECTIVES

• ? To perform contrast‐enhanced ultrasonography (CEUS) using contrast‐tuned imaging (CnTI) technology to detect prostate cancer.
• ? To evaluate the detection of prostate cancer with CnTI compared with conventional grey‐scale and power Doppler ultrasonography.

PAIENTS AND METHODS

• ? In all, 150 patients referred for prostate biopsy were evaluated using transrectal grey‐scale, power Doppler and CnTI ultrasonography.
• ? Biopsy was performed at 10 sites in each patient. If an abnormality was found at any of these three ultrasonography examinations, a biopsy specimen was targeted towards from the corresponding site.
• ? The performances of the three ultrasonography techniques for prostate cancer detection were compared.

RESULTS

• ? Prostate cancer was detected at 383 sites from 73 patients. The combination of these three examinations detected more patients with prostate cancer than grey‐scale (P= 0.002), power Doppler (P= 0.001) or baseline imaging (the combination of grey‐scale and power Doppler; P= 0.031) alone.
• ? By biopsy site, CnTI had higher sensitivity and accuracy (73.1% and 83.7%) than grey‐scale (50.9%; P < 0.001 and 78.8%; P < 0.001) or power Doppler (48.3%; P < 0.001 and 77.7%; P < 0.001), while the specificity was similar for grey‐scale (88.4%), power Doppler (87.8%) and CnTI (87.3%; P > 0.05 in each case). CnTI had higher sensitivity (73.1% vs 62.9%; P < 0.001), specificity (87.3% vs 82.1%; P < 0.001) and accuracy (83.7% vs 77.2%; P < 0.001) than baseline imaging.
• ? The mean Gleason score of CnTI‐positive cases was significantly higher than CnTI‐negative cases (7.1 vs 6.3; P= 0.002).

CONCLUSIONS

• ? CEUS using CnTI technology enables a visualization of the microvasculature associated with prostate cancer.
• ? CnTI technology could be used to guide biopsy and improve the detection rate of prostate cancer.
• ? CnTI technology was able to detect higher grade prostate cancers.

     

Suberoylanilide hydroxamic acid (SAHA) combined with bortezomib inhibits renal cancer growth by enhancing histone acetylation and protein ubiquitination synergistically

What's known on the subject? and What does the study add? The treatment modality for advanced renal cancer is limited and new treatment approaches are urgently needed. Beneficial effects of bortezomib combined with SAHA have recently been reported. However, there are no previous reports of this combination being tested against renal cancer and its further mechanisms of action should be clarified. This study examined the combined effects of these two clinically feasible drugs and showed that the combination inhibits renal cancer cell proliferation by enhancing both protein ubiquitination and histone acetylation synergistically.

OBJECTIVE

• ? To investigate the combined effect of two clinically feasible drugs, the proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA), on human renal cancer cells in vitro and in vivo.

MATERIALS AND METHODS

• ? The effectiveness of the combination of bortezomib (10–20 nm ) and SAHA (1–5 µm ) on renal cancer cells (Caki‐1, ACHN, A‐498, 786‐O, 769‐P) was assessed by MTS assay, colony formation assay, cell cycle analysis, and apoptosis assay.
• ? In vivo efficacy was evaluated using murine subcutaneous (s.c.) tumour models.
• ? Protein ubiquitination, unfolded protein response, histone acetylation, and changes in the expression of HDAC were evaluated by western blotting.

RESULTS

• ? The combination of SAHA and bortezomib induced apoptosis and inhibited cancer cell proliferation synergistically (combination indices <1) and colony formation significantly (P < 0.05).
• ? In s.c. tumour models a 10‐day treatment with a combination of SAHA (50 mg/kg) and bortezomib (60 µg/kg) inhibited tumour growth significantly (P < 0.05).
• ? Mechanistically, SAHA combined with bortezomib enhanced protein ubiquitination synergistically and enhanced histone acetylation by inhibiting the expression of HDACs.

CONCLUSION

• ? SAHA combined with bortezomib inhibits the proliferation of renal cancer cells in vitro and in vivo, and the effectiveness of the combination is due to its synergistic enhancement of histone acetylation and protein ubiquitination.

     

Partial nephrectomy for renal masses ≥ 7 cm: technical, oncological and functional outcomes

What's known on the subject? and What does the study add? Partial nephrectomy for the pT1 renal mass has demonstrated acceptable oncological outcomes in addition to improved overall long‐term survival when compared with radical nephrectomy. Previous reports for lesions ≥7 cm have shown mixed data concerning oncological outcomes and technological success. We demonstrate that partial nephrectomy for renal masses ≥7 cm has acceptable oncological, technical, and functional outcomes. As such, partial nephrectomy should be a surgical option when feasible regardless of tumour size. Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To present outcomes for patients with renal masses ≥7 cm in size who are treated with partial nephrectomy (PN) at our institution and to summarize the cumulative published experience.

PATIENTS AND METHODS

• ? We reviewed our prospectively maintained institutional kidney cancer database and identified patients undergoing PN for tumours >7 cm in size.
• ? Technical, oncological and renal functional data were analyzed and compared with the existing published experience of PNs for tumours >7 cm in size.

RESULTS

• ? In total, 46 patients with 49 renal tumours >7 cm in size who underwent PN were identified.
• ? With a median (range) follow‐up of 13.1 (0.2–170.0) months, there were 16 complications, including four (8.2%) blood transfusions and six (12.2%) urinary fistulae.
• ? The 5‐ and 10‐year overall and renal cell carcinoma (RCC)‐specific survivals were 94.5% and 70.9%. There were five (10.9%) patients who had an upward migration in their chronic kidney disease status after PN.
• ? There were six previous series totalling 280 tumours encompassing the published experience of PN for tumours >7 cm in size. The incidence of urinary fistulae and postoperative haemorrhage, respectively, was in the range 3.3–18.8% and 0–3%.
• ? Although oncological outcomes showed cancer‐specific survival in the range 66–97.0%, series matching PN and RN in patients with T2 RCC show equivalency in RCC‐specific and overall survivals. When reported, PN for tumours >7 cm in size was associated with better renal functional preservation.

CONCLUSION

• ? The findings of the present study show that PN can safely be performed in tumours ≥7 cm in size with acceptable technical, oncological and functional outcomes. Further studies are warranted.

     

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

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

OBJECTIVE

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

PATIENTS AND METHODS

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

RESULTS

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

CONCLUSIONS

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

     

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.

     

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.

     

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.

     

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.

     

Laparoscopic partial nephrectomy: beyond the straightforward T1a

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Complex tumour features (e.g. size, hilar location, multifocality) are generally considered contraindicative for LPN and only a handful of studies reporting encouraging outcomes with more complex tumours. Herein we suggest that in experience hands the benefits of minimally‐invasive surgery may be safely extended to patients with more complex renal masses.

OBJECTIVE

• ? To report on our experience in extending the indications for LPN beyond the single, T1a renal mass assessing the perioperative outcomes in a comparative fashion.

PATIENTS AND METHODS

• ? Retrospective review of consecutive patients undergoing LPN for a renal mass in an academic centre between 2005–2010.
• ? 150 patients were divided into two groups based on tumours characteristics: straightforward T1a (group 1: single, <4 cm, n = 84) and complex (group 2: multiple and/or hilar and/or ≥4 cm, n = 66).
• ? Comparison of demographic, clinical, radiographic and perioperative outcomes (operative times, blood loss, warm ischemia times, intra‐ and postoperative complications).

RESULTS

• ? In group 2, 19 tumours were hilar, 15 were multifocal and 44 measured ≥4 cm; 2 of these criteria were present in 7, and all three in 3 cases.
• ? Warm ischemia times and blood loss were comparable (medians of 21 vs 20 min, and 100 vs 100 mL).
• ? Operative times were longer in group 2 (190 vs 140min, P < 0.001).
• ? Complications occurred in 11.9% and 12.1% of patients in group 1 and 2, with Clavien grade 3 events in 8.3 and 10.9%, respectively (P = 1.00 and P = 0.547).
• ? There were 4 conversions to laparoscopic radical nephrectomy (1 in group 1, 3 in group 2).

CONCLUSION

• ? With adequate laparoscopic expertise, the indications for LPN can be safely extended beyond the single, small, peripheral T1a renal mass. In this series, more complex masses were effectively treated with LPN combining the advantages of minimally‐invasive surgery to those of nephron‐sparing approach.

     

Under-grading of <4 cm renal masses on renal biopsy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is well documented that biopsy of small renal masses is inaccurate and tends to under‐estimate tumour grade compared with surgical specimens. To our knowledge there has not been a study showing grading discrepancy between biopsy and surgical excision in a large population‐based cohort.

OBJECTIVE

• ? To determine whether differences exist in tumour grade between patients who undergo partial nephrectomy (PN) and those who undergo ablation for renal tumours.

PATIENTS AND METHODS

• ? Data was obtained using the Surveillance, Epidemiology and End Results database. Patients with solitary renal tumours of <4 cm treated with ablation or PN and with renal cell carcinoma (RCC) histopathology were identified.
• ? Tissue diagnosis in the ablation specimens was obtained from biopsy reports, whereas tissue from PN specimens was determined from surgical pathology.
• ? Variables analysed included: year of diagnosis, age, sex, race/ethnicity, marital status, population density, education, poverty level, and tumour size.
• ? Stacked bar graphs were created to compare the distributions of grade and histology between the groups. Multinomial logistic regression was used to determine factors independently associated with grade.

RESULTS

• ? In all, 7704 (87.4%) patients underwent PN and 1114 (12.6%) underwent either radiofrequency ablation or cryoablation.
• ? The PN patients were younger at diagnosis (59 vs 68 years, P < 0.001), more likely to be married (70% vs 64%, P < 0.001), and had smaller tumours (2.4 vs 2.6 cm, P < 0.001).
• ? There were no differences in the distribution of histology between the PN and ablation groups.
• ? Tumour grade was significantly lower in tumours treated with ablation.
• ? Compared with grade 1 disease, those undergoing ablation were 30% less likely to have grade 2 (P < 0.001), 30% less likely to have grade 3 (P < 0.001), and 92% less likely to have grade 4 disease (P < 0.01) than those having PN.

CONCLUSIONS

• ? There is a strong association between grade and treatment type in patients with small renal masses after controlling for baseline characteristics.
• ? As grade is determined by different methods, we think that this shows systematic under‐grading in biopsy of small renal masses.

     

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.

     

Evolving practice patterns for the management of small renal masses in the USA

Study Type – Therapy (trend analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Treatment options for small renal masses include radical nephrectomy (RN), partial nephrectomy (PN), ablation, and surveillance. PN provides equivalent oncological as RN for small tumours, but long‐term outcomes for ablation and surveillance are poorly defined. Due to changing techniques and technology, treatment patterns for small renal masses are rapidly developing. Prior studies had analysed utilisation trends for PN and RN to 2006, revealing a relative rise in the rate of PN. However, overall treatment trends including surveillance and ablation had not been studied using a population‐based cohort. It has become increasingly clear that RN is associated with greater renal and cardiovascular deterioration than nephron‐sparing treatments. Thus, it is important to understand current population‐based practice patterns for the treatment of small renal masses to assess whether practitioners are adhering to ever‐changing principles in this field. The present study provides up‐to‐date treatment trends in the USA using a large population‐based cohort.

OBJECTIVE

• ? To describe the changing practice patterns in the management of small renal masses, including the use of surveillance and ablative techniques.

PATIENTS AND METHODS

• ? All patients in the Surveillance, Epidemiology and End Results (SEER) registry treated for renal masses of ≤7 cm in diameter, from 1998 to 2008, were included for analysis.
• ? Annual trends in the use of surveillance, ablation, partial nephrectomy (PN), and radical nephrectomy (RN) were calculated.
• ? Multinomial logistic regression was used to determine the association of demographic and clinical characteristics with treatment method.

RESULTS

• ? In all, 48 148 patients from 17 registry sites with a mean age of 63.4 years were included for analysis.
• ? Between 1998 and 2008, for masses of <2 cm and 2.1–4 cm, there was a dramatic increase in the proportion of patients undergoing PN (31% vs 50%, 16% vs 33%, respectively) and ablation (1% vs 11%, 2% vs 9%, respectively).
• ? In multivariable analysis, later year of diagnosis, male gender, being married, clinically localised disease, and smaller tumours were associated with increased use of PN vs RN. Later year of diagnosis, male gender, being unmarried, smaller tumour, and the presence of bilateral masses were associated with increased use of ablation and surveillance vs RN.

CONCLUSIONS

• ? PN is now used in half of all patients with the smallest renal masses, and its use continues to increase over time.
• ? Ablation and surveillance are less common overall, but there is increased usage over time in select populations.

     

A multicentre, prospective, randomized trial: comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy for distal ureteric stones with renal colic

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? α‐blocker tamsulosin in medical expusion therapy was determined to be safe and effective for distal ureteric stones with renal colic. This trial further demonstrates that the tamsulosin in MET is more efficative and more safer than nifedipine for distal ureteric stones with renal colic.

OBJECTIVE

• ? To determine the comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy (MET) for distal ureteric stones with renal colic.

PATIENTS AND METHODS

• ? We evaluated the comparative efficacy of tamsulosin and nifedipine in MET in a prospective randomized trial of 3189 outpatients from 10 centres in China.
• ? Eligible patients randomly received tamsulosin or nifedipine. Efficacies of the two agents in MET were compared at 4 weeks.
• ? The primary endpoint was overall stone‐expulsion rate.
• ? Secondary endpoints were stone‐expulsion time, rate of pain relief therapy, mean analgesic consumption for renal colic recurrence, and side‐effects incidence.

RESULTS

• ? Stone‐expulsion rates in the tamsulosin group (group 1) were greater than those in the nifedipine group (group 2; P < 0.01).
• ? There was a significant variation in stone‐expulsion rates and times between groups 1 and 2 (P < 0.01); with improvements in stone‐expulsion rate and time significantly better in group 1 than in group 2.
• ? There was a significant variation in the rate of pain relief therapy for renal colic recurrence between groups 1 and 2 (P < 0.01); patients in group 1 required significantly less analgesics than those in group 2 (P < 0.01).
• ? There were no statistically significant differences in side‐effects incidence between the groups.

CONCLUSIONS

• ? Administration of tamsulosin and nifedipine in MET was determined to be safe and effective for distal ureteric stones with renal colic.
• ? Tamsulosin was significantly better than nifedipine in relieving renal colic and facilitating ureteric stone expulsion.