Current pathology keys of renal cell carcinoma

Context

Renal cell carcinoma (RCC) in adults comprises a heterogeneous group of tumours with variable clinical outcomes that range from indolent to overtly malignant. The application of molecular genetic techniques to the study of renal neoplasms has resulted in an improved classification of these entities and a better understanding of the biologic mechanisms responsible for tumour development and progression. The current 2004 World Health Organisation classification of adult renal epithelial neoplasms has expanded rapidly with new categories recently incorporated.

Objective

To review and evaluate the evidence implicating pathologic features and classification of RCC in adults as a tool to approach patients’ prognosis and modulate current therapy.

Evidence acquisition

Members of Committee 3: Pathology, under the auspices of the International Consultation on Urological Diseases and the European Association of Urology (ICUD-EAU) International Consultation on Kidney Cancer, performed a systematic review using PubMed. Participating pathologists discussed pathologic categories and diagnostic features of RCC in adults.

Evidence synthesis

We reviewed and discussed articles and the personal experiences of participating uropathologists.

Conclusions

The conclusions reached by the ICUD-EAU 2010 International Consultation on Kidney Cancer emphasise the appropriate pathologic diagnosis of RCC in adults as a tool to approach patients’ prognosis and modulate current therapy. Further emphasis should be placed on defining risk groups of RCC and diagnostic features of unusual tumours such as familial RCC, translocation RCC, and tubular mucinous and spindle cell carcinoma. A number of recently described entities and morphologic variants of classical categories deserves recognition because they can be important in differential diagnosis and therapy.     

T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6

Background

Evidence suggests that some patients with renal cell carcinoma (RCC) respond to immunomodulatory therapies that activate T lymphocytes. A prerequisite for effective T cell therapy is efficient targeting of effector T cells to the tumour site, yet the molecular basis of T cell recruitment to RCC is unknown. Furthermore, some T cells that naturally infiltrate this cancer are regulatory T cells (Tregs) that may suppress antitumour immune responses.

Objective

Determine the mechanisms of effector and regulatory T cell recruitment to RCC to allow targeted therapy that promotes local anti-tumour immunity.

Design, setting, and participants

Tumour-infiltrating and peripheral blood T cells were collected from 70 patients undergoing nephrectomy for RCC.

Measurements

T cells were analysed by multicolour flow cytometry for expression of 19 chemokine receptors and 7 adhesion molecules. Receptors that were expressed at higher levels on tumour-infiltrating lymphocytes (TILs) compared with matched peripheral blood lymphocytes (PBLs) were analysed further for their ability to mediate migration responses in TILs and for expression of corresponding ligands in tumour tissue.

Results and limitations

Three chemokine receptors—CCR5, CXCR3, and CXCR6—were significantly overexpressed on TILs compared with matched PBLs (n = 16 cases) and were capable of promoting migration in vitro. Their corresponding ligands CCL4-5, CXCL9-11, and CXCL16 were all detected in RCC tissue. However, since they were present in all cases studied, it was not possible to correlate ligand expression with levels of T cell infiltration. Foxp3⁺ Tregs were enriched within TILs compared with matched PBLs and expressed high levels of CCR5, CXCR3, and CXCR6, as well as CCR6, the ligand for which (CCL20) was detectable in RCC tissue.

Conclusions

Our data support a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into RCC tissue and, together with CCR6, in the recruitment of Tregs.     

Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population

Background

Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours.

Objective

Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population.

Design, setting, and participants

Twenty-four French university departments of urology participated in this retrospective study.

Intervention

All patients were treated according to current European Association of Urology guidelines.

Measurements

Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods.

Results and limitations

The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design.

Conclusions

RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.     

Prognostic factors and predictive models in renal cell carcinoma: a contemporary review

Context

The natural history of renal cell carcinoma (RCC) is highly unpredictable. Small renal masses may be accompanied by metastatic disease. Conversely, patients with locally advanced disease may enjoy long-term disease-free survival.

Objective

To review the status of prognostic factors in RCC.

Evidence acquisition

A literature review was performed using the PubMed, MEDLINE, and Cochrane databases for articles published as of February 15, 2010. Electronic articles published ahead of print were also considered. Search was limited to the English language. Search was conducted using the following keywords: renal cell carcinoma, molecular, tissue, markers, blood, urine, progression, prognosis, risk factor, and survival. Studies were selected according to the relevance of the study, the number of patients included, originality, actuality, and clinical applicability of the results.

Evidence synthesis

Four areas of prediction were examined: (1) new RCC diagnostics, (2) RCC grade and stage at diagnosis, (3) disease progression, and (4) disease-specific mortality. All identified reports represented either case series or controlled studies. Although a large number of markers were identified, only a few were validated. Several prognostic factors were integrated in predictive or prognostic models.

Conclusions

Several prognostic factors can help discriminate between favourable and unfavourable RCC phenotypes. Of those, several clinical, pathologic, and biologic markers have been tested and validated, and they are used in predictive and prognostic models. Nonetheless, the search continues, especially for informative markers predicting the response to targeted therapies.     

Sequencing of agents for metastatic renal cell carcinoma: can we customize therapy?

Context

The expanding armamentarium of agents for the therapy of advanced clear cell renal cell carcinoma (RCC) warrants further investigation of optimal patient selection.

Objective

To analyze the second and subsequent line of targeted therapies for advanced RCC while integrating clinical and molecular markers and imaging.

Evidence acquisition

Data were acquired from research published in peer-reviewed literature or presented at major conferences.

Evidence synthesis

Following first-line vascular endothelial growth factor (VEGF) inhibitors, second-line therapy with everolimus, a mammalian target of rapamycin inhibitor, and axitinib, a VEGF receptor tyrosine kinase inhibitor, have demonstrated benefits in progression-free survival (PFS). Sorafenib, pazopanib, and axitinib have demonstrated extension of PFS following cytokines. Optimal patient selection based on biomarkers is undergoing investigation. Clinical trials evaluating novel agents and combinations should be preferred.

Conclusions

Currently, the sequence of therapy is based on patient and physician decision, which may be influenced by comorbidities and toxicity profiles.     

Routine adrenalectomy in patients with locally advanced renal cell cancer does not offer oncologic benefit and places a significant portion of patients at risk for an asynchronous metastasis in a solitary adrenal gland

Background

The indications for the removal of the ipsilateral adrenal gland in patients with renal cell carcinoma (RCC) and the long-term outcomes have not been well studied.

Objective

We evaluated the risk of synchronous and asynchronous adrenal involvement in patients with RCC and the effect of adrenalectomy on recurrence and survival in a large, single-institution cohort.

Design, setting, and participants

From 1970 to 2006, 4018 consecutive patients with RCC treated by surgical extirpation (radical nephrectomy [RN]: 3107; partial nephrectomy [PN]: 911) from Mayo Clinic were studied for adrenal involvement. Risk of asynchronous adrenal metastasis and cancer-specific survival (CSS) were also compared between those who underwent concomitant ipsilateral adrenalectomy (n = 1541) and those who did not (n = 2477) using multivariate Cox models.

Intervention

Surgical removal of the adrenal gland at the time of kidney tumor resection.

Measurements

Primary outcome is cancer specific survival; secondary outcomes are incidence of synchronous and asynchronous adrenal metastases.

Results and limitations

Median postoperative follow-up among those still alive was 8.2 yr (interquartile range [IQR]: 5.3-13.6). Synchronous ipsilateral adrenal involvement was rare (n = 88; 2.2%). Ipsilateral adrenalectomy at the time of nephrectomy did not lower the risk of subsequent adrenal metastasis (hazard ratio [HR]: 0.96; 95% confidence interval [CI], 0.64-1.42) or improve CSS (HR: 1.08; 95% CI, 0.95-1.22). The development of asynchronous adrenal metastasis occurred in 147 patients (3.7%) at a median of 3.7 yr (IQR: 1.2-7.7) after initial surgery. The risk of developing an ipsilateral versus a contralateral asynchronous adrenal metastasis was equivalent at 10 yr in those who did not undergo adrenalectomy at initial surgery. This study is limited by its single-institution, nonrandomized nature.

Conclusions

Routine ipsilateral adrenalectomy in patients with high-risk features does not appear to offer any oncologic benefit while placing a significant portion of patients at risk for metastasis in a solitary adrenal gland. Therefore, adrenalectomy should only be performed with radiographic or intraoperative evidence of adrenal involvement.     

Treatment of localised renal cell carcinoma

Context

The increasing incidence of localised renal cell carcinoma (RCC) over the last 3 decades and controversy over mortality rates have prompted reassessment of current treatment.

Objective

To critically review the recent data on the management of localised RCC to arrive at a general consensus.

Evidence acquisition

A Medline search was performed from January 1, 2004, to May 3, 2011, using renal cell carcinoma, nephrectomy (Medical Subject Heading [MeSH] major topic), surgical procedures, minimally invasive (MeSH major topic), nephron-sparing surgery, cryoablation, radiofrequency ablation, surveillance, and watchful waiting.

Evidence synthesis

Initial active surveillance (AS) should be a first treatment option for small renal masses (SRMs) <4 cm in unfit patients or those with limited life expectancy. SRMs that show fast growth or reach 4 cm in diameter while on AS should be considered for treatment. Partial nephrectomy (PN) is the established treatment for T1a tumours (<4 cm) and an emerging standard treatment for T1b tumours (4-7 cm) provided that the operation is technically feasible and the tumour can be completely removed. Radical nephrectomy (RN) should be limited to those cases where the tumour is not amenable to nephron-sparing surgery (NSS). Laparoscopic radical nephrectomy (LRN) has benefits over open RN in terms of morbidity and should be the standard of care for T1 and T2 tumours, provided that it is performed in an advanced laparoscopic centre and NSS is not applicable. Open PN, not LRN, should be performed if minimally invasive expertise is not available. At this time, there is insufficient long-term data available to adequately compare ablative techniques with surgical options. Therefore ablative therapies should be reserved for carefully selected high surgical risk patients with SRMs <4 cm.

Conclusions

The choice of treatment for the patient with localised RCC needs to be individualised. Preservation of renal function without compromising the oncologic outcome should be the most important goal in the decision-making process.     

The epidemiology of renal cell carcinoma

Context

Kidney cancer is among the 10 most frequently occurring cancers in Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed yearly and 116 000 people die from the disease. Approximately 90% of all kidney cancers are renal cell carcinomas (RCC).

Objective

The causes of RCC are not completely known. We have reviewed known aetiologic factors.

Evidence acquisition

The data provided in the current review are based on a thorough review of available original and review articles on RCC epidemiology with a systemic literature search using Medline.

Evidence synthesis

Smoking, overweight and obesity, and germline mutations in specific genes are established risk factors for RCC. Hypertension and advanced kidney disease, which makes dialysis necessary, also increase RCC risk. Specific dietary habits and occupational exposure to specific carcinogens are suspected risk factors, but results in the literature are inconclusive. Alcohol consumption seems to have a protective effect for reasons yet unknown. Hardly any information is available for some factors that may have a high a priori role in the causation of RCC, such as salt consumption.

Conclusions

Large collaborative studies with uniform data collection seem to be necessary to elucidate a complete list of established risk factors of RCC. This is necessary to make successful prevention possible for a disease that is diagnosed frequently in a stage where curative treatment is not possible anymore.     

Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma

Background

To our knowledge, the impact of venous tumour thrombus (VTT) consistency in patients affected by renal cell carcinoma (RCC) has never been addressed.

Objective

To analyse the effect of VTT consistency on cancer-specific survival (CSS).

Design, setting, and participants

We retrospectively analysed 174 consecutive patients with RCC and renal vein or inferior vena cava (IVC) VTT who underwent surgical treatment between 1989 and 2007 at our institute.

Intervention

All patients underwent radical nephrectomy and thrombectomy.

Measurements

Pathologic specimens were reviewed by a single uropathologist. In addition to traditional pathologic features, the morphologic aspect of the tumour thrombus was evaluated to distinguish solid from friable patterns. The prognostic role of thrombus consistency (solid vs friable) on CSS was assessed by means of Cox regression models.

Results and limitations

The VTT was solid in 107 patients (61.5%) and friable in 67 patients (38.5%). The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumour grade, higher pathologic stage, and simultaneous perinephric fat invasion (all p < 0.05). The median follow-up was 24 mo. The median CSS was 33 mo; the median CSS was 8 mo in patients with a friable VTT and 55 mo in patients with a solid VTT (p < 0.001). On multivariable analyses, the presence of a friable VTT was an independent predictor of CSS (p = 0.02). The power of our conclusion may be somewhat limited by the relatively small study population and the retrospective nature of the study.

Conclusions

In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSS. If our finding is confirmed by further studies, the consistency of the tumour thrombus should be introduced into routine pathologic reports to provide better patient risk stratification.     

Clinicopathologic characteristics and prognosis of synchronous multifocal gastric carcinomas

Background

We sought to define differences between multifocal and solitary gastric carcinoma to decrease the risk of missing a cancer while resecting another more evident carcinoma.

Methods

We retrospectively examined clinicopathologic characteristics of multifocal gastric carcinoma including anatomic distribution and postoperative survival.

Results

Multifocal gastric carcinoma was seen more frequently when patients were older and when the largest tumor was small and at an early stage. More than half of accessory lesions were located near the main tumor. No significant difference in postoperative survival was seen between patients with multifocal and solitary carcinoma, whether early or advanced.

Conclusions

The entire stomach should be examined carefully before and during resection, especially when local or endoscopic surgery is performed.     

Basic research in kidney cancer

Context

Advances in basic research will enhance prognosis, diagnosis, and treatment of renal cancer patients.

Objective

To discuss advances in our understanding of the molecular basis of renal cancer, targeted therapies, renal cancer and immunity, and genetic factors and renal cell carcinoma (RCC).

Evidence acquisition

Data on recently published (2005-2011) basic science papers were reviewed.

Evidence synthesis

Advances in basic research have shown that renal cancers can be subdivided based on specific genetic profiles. Now that this molecular basis has been established, it is becoming clear that additional events play a major role in the development of renal cancer. For example, aberrant chromatin remodelling appears to be a main driving force behind tumour progression in clear cell RCC. A large number of potential biomarkers have emerged using various high-throughput platforms, but adequate biomarkers for RCC are still lacking. To bring the potential biomarkers and biomarker profiles to the clinical arena is a major challenge for the field.The introduction of tyrosine kinase inhibitors (TKIs) for therapy has shifted the interest away from immunologic approaches. Nevertheless, a wealth of evidence supports immunotherapy for RCC. Interestingly, studies are now appearing that suggest a combination of TKI and immunotherapy may be beneficial.Thus far, little attention has been paid to patient-specific differences. With high-throughput methods becoming cheaper and with the advances in sequencing possibilities, this situation is expected to change rapidly.

Conclusions

Great strides have been made in the understanding of molecular mechanisms of RCC. This has led this field to the enviable position of having a range of molecularly targeted therapies. Large sequencing efforts are now revealing more and more genes responsible for tumour development and progression, offering new targets for therapy. It is foreseen that through integration of high-throughput platforms, personalised cancer treatment for RCC patients will become possible.     

Reassessing the Current UICC/AJCC TNM Staging for Renal Cell Carcinoma

Context

The outcome prediction for renal cell cancer (RCC) remains controversial, and although many parameters have been tested for prognostic significance, only a few have achieved widespread acceptance in clinical practice. The TNM staging system defines local extension of the primary tumour (T), involvement of regional lymph nodes (N), and presence of distant metastases (M).

Objective

This review focuses on reassessing the current TNM staging system for RCC.

Evidence acquisition

A literature search in English was performed using the National Library of Medicine database and the following keywords: renal cell cancer, kidney neoplasm, and staging. We scrutinized 1952 references, and 62 were selected for review based on their pertinence, study size, and overall contribution to the field.

Evidence synthesis

The prognostic significance of tumour size for localized RCC has been investigated in a large number of studies. As a consequence, many modifications of the TNM staging system were primarily made to the size cut points between stage I and II tumours. The latest three revisions of the TNM system are systematically reviewed. For the heterogeneous group of locally advanced RCCs, involving different anatomic structures surrounding the kidney, the situation is still the subject of controversial scientific dispute. In detail, perirenal fat invasion, direct infiltration of the ipsilateral adrenal gland, invasion of the urinary collecting system, infiltration of renal sinus fat, and vena cava and renal vein thrombosis are disputed. Finally, staging of lymph node metastases and distant metastatic disease is discussed.

Conclusions

Special emphasis should be put on renal sinus invasion for stage evaluation. Retrospective studies relying on material collected at a time when no emphasis was placed on adequate sampling of the renal sinus should be treated with caution. In view of new treatment opportunities, the current TNM staging system of RCC and any other staging system must be dynamic.     

Familial renal cell carcinoma from the Swedish Family-Cancer Database

Background

Reliable data on familial risks are important for clinical counselling and cancer genetics.

Objective

To evaluate familial risks for renal cell carcinomas (RCC) through parental and sibling probands in the largest available dataset.

Design, setting, and participants

This study examined the Swedish Family-Cancer Database on 12.2 million individuals, which contains families with parents and offspring. Cancer data were retrieved from the Swedish Cancer Registry for the years 1961-2008, including 8513 patients with RCC.

Measurements

Familial risk for offspring was defined through standardised incidence ratios (SIRs) and adjusted for many variables, including a proxy for smoking and obesity.

Results and limitations

The familial risk for RCCs was 1.75 when a parent and 2.61 when a sibling was diagnosed with any kidney cancer. Also, RCCs were shown to be associated with prostate cancer (PCa) when parents or parents and siblings were diagnosed with PCa. Among siblings, the associations of RCC with melanoma, non-Hodgkin's lymphoma, and urinary bladder and papillary thyroid tumours were found. None of the results differed significantly after excluding the families with cancer pathognomonic of a von Hippel-Lindau (VHL) disease. Limitations of this study include the small number of familial cases (229 familial cases).

Conclusions

The present analysis showed a high familiarity for RCC, and recessive effects may be important for familial aggregation of RCC. As a novel association, offspring RCC was in excess when parents or parents and siblings were diagnosed with PCa. There is familial clustering beyond VHL and the recent low-risk gene that probably explains a small proportion of the observed familial clustering.     

Hyperthermic intraperitoneal chemoperfusion is an option for treatment of peritoneal carcinomatosis in children

Background

Gastrointestinal carcinomas in childhood are rare and frequently present at an advanced stage. Besides lymphatic and distant organ metastasis, peritoneal carcinomatosis may be detected and has a poor prognosis. In addition to surgery and intravenous chemotherapy, hyperthermic intraperitoneal chemoperfusion (HIPEC) may be an option for selected patients. Our aim was to demonstrate the feasibility of the method and to discuss possible indications.

Methods

After treating a series of adult patients, HIPEC for peritoneal carcinomatosis from a signet cell carcinoma of the colon was performed intraoperatively in a 12-year-old boy. We gave mitomycin C at a dose of 30 mg/m² over 90 minutes at maximum temperature of 41.2°C. We performed intraoperative drug level monitoring and daily postoperative liver and kidney function tests and differential blood counts.

Results

Hyperthermic intraperitoneal chemoperfusion was performed according to protocol without complications. Perfusate and venous drug levels were similar to those in an adult case. The patient had an uneventful recovery, and serum chemistry and blood count returned to normal after a week. The boy lived for 36 months after initial presentation. Sixteen months after HIPEC, still with excellent quality of life, an elevated carcinoembryonic antigen (CEA) indicated recurrence. Thirty months after HIPEC, he died of progressive recurrent disease.

Conclusions

Hyperthermic intraperitoneal chemoperfusion as performed in adults may be beneficial to children with peritoneal carcinomatosis and merits further study.     

Differentiation of renal cell carcinoma subtypes by multislice computerized tomography

Purpose

We differentiated renal cell carcinoma subtypes using multislice computerized tomography (CT).

Materials and Methods

We reviewed the CT images of 87 patients with renal cell carcinoma. Three subtypes of renal cell carcinoma were noted, including clear cell in 37 cases, papillary in 26 and chromophobe in 24. Biphasic CT (unenhanced, corticomedullary and excretory phases) was done in all patients. We compared patient age and sex, tumor size, enhancement degree and pattern (homogeneous, heterogeneous and predominantly peripheral), the presence or absence of calcification or cystic degeneration (necrotic or hemorrhagic areas within the tumor) and tumor spreading patterns, including perinephric change, venous invasion and lymphadenopathy, in the 3 subtypes.

Results

The degree of enhancement was significantly different among the 3 subtypes in the corticomedullary and excretory phases (p <0.001). Cystic degeneration was more evident in the clear cell subtype than in the other subtypes regardless of tumor size (p <0.001). A hypervascular pattern (higher tumor enhancement after contrast material injection due to higher vascularity) was noted in 48.6% of clear cell subtype in comparison to 15.4% of papillary and 4.2% of chromophobe subtypes (p <0.001). The chromophobe subtype showed homogeneous enhancement in 75% of cases in comparison to 45% and 65% of clear cell and papillary subtypes (p >0.05). Calcification was evident in 21.6%, 23.1% and 25% of clear cell, papillary and chromophobe subtypes, respectively (p >0.05).

Conclusions

To differentiate the subtypes of renal cell carcinoma the degree of enhancement is the most valuable parameter. The presence or absence of cystic degeneration, vascularity and enhancement patterns can serve supplemental role in differentiating renal cell carcinoma subtypes.     

Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy

Background

Percutaneous needle core biopsy has become established in the management of small renal masses ≤4 cm (SRMs). Recent series have reported success rates of ≥80%. Nondiagnostic results continue to be problematic.

Objective

To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy.

Design, setting, and participants

Patients undergoing renal tumor biopsy (RTB) for suspected renal cell carcinoma (RCC) were included in a prospectively maintained database.

Measurements

The database was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy. Outcomes of patients with nondiagnostic biopsy were determined. Patients undergoing repeat biopsy were identified and their outcomes analyzed.

Results and limitations

Three hundred forty-five biopsies were performed (mean diameter: 2.5 cm). Biopsy was diagnostic in 278 cases (80.6%) and nondiagnostic in 67 cases (19.4%). Among diagnostic biopsies, 221 (79.4%) were malignant, 94.1% of which were RCC. Histologic subtyping and grading of RCC was possible in 88.0% and 63.5% of cases, respectively. Repeat biopsy was performed in 12 of the 67 nondiagnostic cases, and a diagnosis was possible in 10 (83.3%). Eight lesions were malignant and two were oncocytic neoplasms. Pathology was available for 15 masses after initial nondiagnostic biopsy; 11 (73%) were malignant. Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis. Grade 1 complications were experienced in 10.1% of cases, with no major bleeding and no seeding of the biopsy tract. There was one grade 3a complication (0.3%).This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates. Repeat biopsy was not standard practice prior to this analysis.

Conclusions

RTB can be performed safely and accurately in the investigation of renal masses ≤4 cm. A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy. Repeat biopsy can be performed with similar accuracy, providing a diagnosis for most patients.     

Vaccine Therapy in Patients with Renal Cell Carcinoma

Context

Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans. Although immunotherapy is currently much less used than in the past, it remains an important option that warrants further exploration.

Objective

To examine the current status of vaccine therapy for RCC and to provide information on relevant clinical studies.

Evidence acquisition

We reviewed recent literature on Medline (2003–2008, using the keywords renal cell carcinoma, cancer vaccines, active immunotherapy, and dendritic cells). Subsequent references were identified from reference list of retrieved articles. Quality assessment included prospective phase 1–3 trials and critical evaluations with low numbers of patients.

Evidence synthesis

Therapeutic vaccines can be divided in autologous tumour cell–based vaccines, genetically modified tumour cell–based and dendritic cell (DC)–based vaccines, and peptide-based vaccines. To date, only two randomised, adjuvant, phase 3 studies investigating RCC vaccines have been published. Autologous tumour cell vaccine (Reniale) improved the 5-yr progression-free survival (PFS) for high-risk nonmetastatic RCC patients at all tumour stages when administered after nephrectomy. The benefit was clearer in the T3 group. A per-protocol analysis revealed a statistically significant PFS and overall survival (OS) in favour of the vaccine. Autologous tumour-derived heat shock protein peptide complex (HSPPC-96; vitespen) could not significantly improve recurrence-free survival in RCC patients at high risk for recurrence after nephrectomy, but did so in intermediate risk patients. DC vaccination in metastatic RCC (mRCC) patients is safe and can induce antigen-specific immune response and obtain tumour regression in a subset of patients.

Conclusions

RCC vaccines have much less toxicity than other current therapies and remain an important area for further research. Reniale has shown significant benefit as an adjuvant RCC vaccine. Vitespen seems promising as an adjuvant treatment in earlier stage disease. A possible area of research is the use of RCC vaccines with immune-enhancing or antiangiogenic agents in the adjuvant setting.     

Prognostic and Therapeutic Impact of the Histopathologic Definition of Parenchymal Epithelial Renal Tumors

Context

In the last few years, the treatment of renal cell carcinoma (RCC) has progressed significantly, and some histopathologic issues have become important for selection and follow-up after medical and surgical therapies.

Objective

The aim of this collaborative article is to review the most recent literature on the role of traditional histopathologic features obtained from renal core biopsy or nephrectomy specimens in the management of confined, locally advanced, and metastatic RCC.

Evidence acquisition

A nonsystematic review of the literature was performed in April 2010 using the Medline database. Multiple free-text searches were performed for the following items: renal cell carcinoma, clear cell, papillary, chromophobe, histologic* subtype*, histotype*, nuclear grade*, necrosis, sarcomatoid differentiation, biopsy, molecular marker*, and cytogenetic marker*. A total of 2369 records were retrieved from Medline, and 263 full-text studies were considered and partially included in the present review. A panel of experts reached consensus on the main subheadings of this paper.

Evidence synthesis

Core needle biopsies can provide important information that is useful to avoid the overtreatment of benign tumors and to help plan watchful waiting or minimally invasive treatments in selected patients. Tumor histotype is fundamental in the pathologic report. In the context of integrated prognostic systems, the combination of the most important clinical and pathologic factors (TNM stage, Fuhrman nuclear grade, presence of necrosis, microvascular invasion, and sarcomatoid dedifferentiation) allows us to reach a high prognostic accuracy. These models can be used to select patients suitable for adjuvant protocols, to design an appropriate follow-up schedule, and to provide careful patient counseling. Molecular and cytogenetic markers should be further evaluated.

Conclusions

The histopathologic definition of parenchymal epithelial renal tumors is fundamental to plan the management and follow-up of patients with locally confined, locally advanced, and metastatic RCC.