Tag Archive for: #KidneyCancer

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Article of the month: Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community and a video prepared by the authors; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, we recommend this one. 

Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

William K. Gray*, Jamie Day*, Tim W. R. Briggs* and Simon Harrison*

*Getting it Right First Time Programme, NHS England and NHS Improvement, London, UK and Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK

Abstract

Objectives

To investigate volume–outcome relationships in nephrectomy and cystectomy for cancer.

Materials and Methods

Data were extracted from the UK Hospital Episodes Statistics database, which records data on all National Health Service (NHS) hospital admissions in England. Data were included for a 5‐year period (April 2013–March 2018 inclusive) and data on emergency and paediatric admissions were excluded. Data were extracted on the NHS trust and surgeon undertaking the procedure, the surgical technique used (open, laparoscopic or robot‐assisted) and length of hospital stay during the procedure. This dataset was supplemented by data on mortality from the UK Office for National Statistics. A number of volume thresholds and volume measures were investigated. Multilevel modelling was used to adjust for hierarchy and confounding factors.

Results

Data were available for 18 107 nephrectomy and 6762 cystectomy procedures for cancer. There was little evidence of trust or surgeon volume influencing readmission rates or mortality. There was some evidence of shorter length of hospital stay for high‐volume surgeons, although the volume measure and threshold used were important.

Conclusions

We found little evidence that further centralization of nephrectomy or cystectomy for cancer surgery will improve the patient outcomes investigated. It may be that length of stay can be optimized though training and support for lower‐volume centres, rather than further centralization.

 

Video: Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

Abstract

Objectives

To investigate volume–outcome relationships in nephrectomy and cystectomy for cancer.

Materials and Methods

Data were extracted from the UK Hospital Episodes Statistics database, which records data on all National Health Service (NHS) hospital admissions in the England. Data were included for a 5‐year period (April 2013–March 2018 inclusive) and data on emergency and paediatric admissions were excluded. Data were extracted on the NHS trust and surgeon undertaking the procedure, the surgical technique used (open, laparoscopic or robot‐assisted) and length of hospital stay during the procedure. This dataset was supplemented by data on mortality from the UK Office for National Statistics. A number of volume thresholds and volume measures were investigated. Multilevel modelling was used to adjust for hierarchy and confounding factors.

Results

Data were available for 18 107 nephrectomy and 6762 cystectomy procedures for cancer. There was little evidence of trust or surgeon volume influencing readmission rates or mortality. There was some evidence of shorter length of hospital stay for high‐volume surgeons, although the volume measure and threshold used were important.

Conclusions

We found little evidence that further centralization of nephrectomy or cystectomy for cancer surgery will improve the patient outcomes investigated. It may be that length of stay can be optimized though training and support for lower‐volume centres, rather than further centralization.

Article of the month: Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores

Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urology community and a video prepared by the authors; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores

Francesco Porpiglia*, Daniele Amparore*, Enrico Checcucci*, Matteo Manfredi*, Ilaria Stura, Giuseppe Migliaretti, Riccardo Autorino, Vincenzo Ficarra§ and Cristian Fiori*

 

*Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, Department of Public Health and Paediatric Sciences, School of Medicine, University of Turin, Orbassano (Turin), Italy, Division of Urology, VCU Health, Richmond, VA, USA, and §Urological Section, Department of Human and Paediatric Pathology, University of Messina, Messina, Italy

 

Abstract

Objectives

To apply the standard PADUA and RENAL nephrometry score variables to three‐dimensional (3D) virtual models (VMs) produced from standard bi‐dimensional imaging, thereby creating 3D‐based (PADUA and RENAL) nephrometry scores/categories for the reclassification of the surgical complexity of renal masses, and to compare the new 3D nephrometry score/category with the standard 2D‐based nephrometry score/category, in order to evaluate their predictive role for postoperative complications.

Materials and Methods

All patients with localized renal tumours scheduled for minimally invasive partial nephrectomy (PN) between September 2016 and September 2018 underwent 3D and 2D nephrometry score/category assessments preoperatively. After nephrometry score/category evaluation, all the patients underwent surgery. Chi‐squared tests were used to evaluate the individual patients’ grouping on the basis of the imaging tool (3D VMs and 2D imaging) used to assess the nephrometry score/category, while Cohen’s κ coefficient was used to test the concordance between classifications. Receiver‐operating characteristic curves were produced to evaluate the sensitivity and specificity of the 3D nephrometry score/category vs the 2D nephrometry score/category in predicting the occurrence of postoperative complications. A general linear model was used to perform multivariable analyses to identify predictors of overall and major postoperative complications.

Results

A total of 101 patients were included in the study. The evaluation of PADUA and RENAL nephrometry scores via 3D VMs showed a downgrading in comparison with the same scores evaluated with 2D imaging in 48.5% and 52.4% of the cases. Similar results were obtained for nephrometry categories (29.7% and 30.7% for PADUA risk and RENAL complexity categories, respectively). The 3D nephrometry score/category demonstrated better accuracy than the 2D nephrometry score/category in predicting overall and major postoperative complications (differences in areas under the curve for each nephrometry score/category were statistically significant comparing the 3D VMs with 2D imaging assessment). Multivariable analyses confirmed 3D PADUA/RENAL nephrometry category as the only independent predictors of overall (P = 0.007; P = 0.003) and major postoperative complications (P = 0.03; P = 0.003).

Conclusions

In the present study, we showed that 3D VMs were more precise than 2D standard imaging in evaluating the surgical complexity of renal masses according to nephrometry score/category. This was attributable to a better perception of tumour depth and its relationships with intrarenal structures using the 3D VM, as confirmed by the higher accuracy of the 3D VM in predicting postoperative complications.

Editorial: Will three‐dimensional models change the way nephrometric scoring is carried out?

There has been an increase in the extent to which imaging is used for preoperative planning of complex urological procedures. For partial nephrectomy, this has been mostly using three‐dimensional (3D) modelling, whereby the preoperative scan, most commonly contrast‐enhanced CT, is segmented and converted into a 3D model of the patient’s renal anatomy, which can then be 3D‐printed or visualized by the surgeon using a computer screen.

In this issue of BJUI, Porpiglia et al. [1] propose the use of 3D models, visualized using a computer for preoperative nephrometric scoring (PADUA and RENAL) of 101 patients to predict postoperative complications. In this preliminary study, they compare the visual scores obtained by two urologists when evaluating only a 3D model, against the scores of two urologists obtained when evaluating only CT images. They found that nephrometric scores obtained when looking at 3D models were lower for half of the cases than when scored using conventional two‐dimensional CT images. Furthermore, they show that for the 101 patients the scores obtained using 3D information were able to give an improved prediction of postoperative complications. The reason for the improved prediction of postoperative complications using 3D modelling is attributed to a better perception of tumour depth and its relationships with intrarenal structures. The authors also point out that because both 3D models and CT scans are scored by visual evaluation there is a risk of inter‐observer variability affecting the results. Overall, this paper introduces an exciting new topic of research in using advanced image analysis techniques for nephrometric scoring.

Many further opportunities exist for developing these ideas of using quantitative image analysis to improve planning and scoring for partial nephrectomy. Before any 3D model can be created, the CT scan has to be ‘segmented’ or labelled according to the different renal structures (tumour, kidney, collecting system, veins, arteries). Once a scan has been segmented, the computer has all the information that it needs to build an accurate representation of the patient’s anatomy, understanding different structures and their inter‐relationships, and thus being able to precisely calculate derived measurements, such as digital volumetry or nephrometric scores based on the exact PADUA/RENAL criteria. Furthermore, novel and more complex nephrometric scores that use segmentation map descriptors could be developed and fitted to postoperative data to further improve predictions. Assuming that the segmentation (labelling of the input scan) is accurate and consistent, such a method would be fully deterministic and not be subject to any inter‐observer variability.

Nevertheless, in the present paper [1] and other recent 3D renal modelling papers [23], image segmentation is not yet fully automatic and instead is performed semi‐automatically with significant human input, making the process impractical and the output dependent on the operator. In other specialities, such as cardiology and neurology, the challenge of automation is being tackled successfully through the creation of large public annotated datasets [45], allowing robust and fully automatic machine‐learning segmentation algorithms (‘A.I.’) to be developed [4]. The creation of a multi‐institutional open‐source dataset of annotated renal CT scans would pave the way for increased research and progress towards automatic, reliable and quantitative image analysis tools for kidney cancer. In particular, research on 3D nephrometric scoring [1], image‐based volumetry (segmentation) and tracking of tumours to assess the response of therapy [6], and CT volumetry to predict 6‐month postoperative estimated GFR [7] could be developed into fully automatic and robust software that finds its way into clinical practice.In conclusion, this paper [1] on 3D models for nephrometric scoring outlines another exciting new way in which advanced image analysis techniques might improve nephrometric scoring and the prediction of complications.

by Lorenz Berger and Faiz Mumtaz

References

  1. Porpiglia FAmparore DCheccucci E et al. Three‐dimensional virtual imaging of the renal tumors: a new tool to improve the accuracy of nephrometric scores. BJU Int 2019; 124: 945-54
  2. Hyde ERBerger LURamachandran N et al. Interactive virtual 3D models of renal cancer patient anatomies alter partial nephrectomy surgical planning decisions and increase surgeon confidence compared to volume‐rendered images. Int J Comput Assist Radiol Surg 201914723
  3. Shirk JDKwan LSaigal CThe use of 3‐dimensional, virtual reality models for surgical planning of robotic partial nephrectomy. Urology 201912592– 7
  4. Suinesiaputra ASanghvi MMAung N et al. Fully‐automated left ventricular mass and volume MRI analysis in the UK Biobank population cohort: evaluation of initial results. Int J Cardiovasc Imaging 201834281
  5. Menze BHJakab ABauer S et al. The multimodal brain tumor image segmentation benchmark (BRATS). IEEE Trans Med Imaging 2015341993– 2024
  6. Smith ADLieber MLShah SNAssessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast‐enhanced CT. Am J Roentgenol 2010194157– 65
  7. Corradi RKabra ASuarez M et al. Validation of 3‐D volumetric based renal function prediction calculator for nephron sparing surgery. Int Urol Nephrol 201749615

 

 

 

 

Video: Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores

Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores

Abstract

Objectives

To apply the standard PADUA and RENAL nephrometry score variables to three‐dimensional (3D) virtual models (VMs) produced from standard bi‐dimensional imaging, thereby creating three‐dimensional (3D)‐based (PADUA and RENAL) nephrometry scores/categories for the reclassification of the surgical complexity of renal masses, and to compare the new 3D nephrometry score/category with the standard 2D‐based nephrometry score/category, in order to evaluate their predictive role for postoperative complications.

Materials and Methods

All patients with localized renal tumours scheduled for minimally invasive partial nephrectomy (PN) between September 2016 and September 2018 underwent 3D and 2D nephrometry score/category assessments preoperatively. After nephrometry score/category evaluation, all the patients underwent surgery. Chi‐squared tests were used to evaluate the individual patients’ grouping on the basis of the imaging tool (3D VMs and 2D imaging) used to assess the nephrometry score/category, while Cohen’s κ coefficient was used to test the concordance between classifications. Receiver‐operating characteristic curves were produced to evaluate the sensitivity and specificity of the 3D nephrometry score/category vs the 2D nephrometry score/category in predicting the occurrence of postoperative complications. A general linear model was used to perform multivariable analyses to identify predictors of overall and major postoperative complications.

Results

A total of 101 patients were included in the study. The evaluation of PADUA and RENAL nephrometry scores via 3D VMs showed a downgrading in comparison with the same scores evaluated with 2D imaging in 48.5% and 52.4% of the cases. Similar results were obtained for nephrometry categories (29.7% and 30.7% for PADUA risk and RENAL complexity categories, respectively). The 3D nephrometry score/category demonstrated better accuracy than the 2D nephrometry score/category in predicting overall and major postoperative complications (differences in areas under the curve for each nephrometry score/category were statistically significant comparing the 3D VMs with 2D imaging assessment). Multivariable analyses confirmed 3D PADUA/RENAL nephrometry category as the only independent predictors of overall (P = 0.007; P = 0.003) and major postoperative complications (P = 0.03; P = 0.003).

Conclusions

In the present study, we showed that 3D VMs were more precise than 2D standard imaging in evaluating the surgical complexity of renal masses according to nephrometry score/category. This was attributable to a better perception of tumour depth and its relationships with intrarenal structures using the 3D VM, as confirmed by the higher accuracy of the 3D VM in predicting postoperative complications.

December 2019 – About the cover

The lead authors of this month’s selected article (Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores) are from the University of Turin, Italy (UNITO). This university was founded in 1404 making it one of the oldest universities in the World. It has been through some turbulent times but more recently can claim three nobel prize winners: Salvador LuriaRenato Dulbecco and Rita Levi-Montalcini.

The cover image shows the city of Turin at sunset. Turin sits mainly on the Po River and it is surrounded by the Western Alps. As the 10th most visited city in Italy it is known for The shroud of Turin, and its football teams (Juventus and Torino). It is also a cultural centre with many theatres, restaurants, art galleries, palaces, parks and churches.

 

 

©istock.com/fabio lamanna

 

Article of the month: Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community and the authors have also kindly produced a video describing their work. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Cedric Lebacle* , Karim Bensalah, Jean-Christophe Bernhard§, Laurence AlbigesBrigitte Laguerre**, Marine Gross-Goupil††, Herve Baumert‡‡, Herve Lang§§, Thibault Tricard§§, Brigitte Duclos¶¶, Armelle Arnoux***, Celine Piedvache***, Jean-Jacques Patard††† and Bernard Escudier

 

*Department of Urology, Bicêtre University Hospital, Assistance Publique-Hôpitaux de Paris, APHP, University Paris-Saclay, Le Kremlin-Bicêtre, Department of Urology, Pontchaillou University Hospital, Rennes, Department of Urology, Bordeaux University Hospital, Pellegrin Hospital, §French Research Network on Kidney Cancer UroCCR, Bordeaux, Department of Medicine, Gustave Roussy, University Paris-Saclay, Villejuif, **Department of Oncology, Eugene Marquis Centre, Rennes, ††Department of Medical Oncology, Bordeaux University Hospital, Saint-André Hospital, Bordeaux, ‡‡Department of Urology, Saint-Joseph Hospital, Paris, §§Department of Urology, Nouvel Hôpital Civil, ¶¶Department of Oncology, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, ***Paris-Sud Clinical Research Unit, Department of Statistics, Bicêtre University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre and †††Department of Urology, Mont de Marsan Hospital, Mont de Marsan, France

 

Abstract

Objective

To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function.

Patients and Methods

Patients with cT2aN0NxM0 clear‐cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7–10 mg, was administered twice daily, for 2–6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib.

Results

Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5  (70–98) mm and 11 (7–11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III–V post‐surgery complications. At 2‐year follow‐up, six patients had metastatic progression, and two had a recurrence.

Conclusion

Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.

Editorial: Expanding the feasibility of nephron‐sparing surgery: time for a paradigm shift?

With the rapid implementation of ‘targeted’ therapies, kidney cancer has entered a new era where old paradigms are being challenged, and new ones can be explored. The idea of delivering ‘neoadjuvant’ systemic therapy to alter the surgical treatment of advanced RCC was suggested in this same journal ~10 years ago as a proof‐of‐concept study [1]. Since then, a plethora of small case series has investigated the safety and feasibility of different targeted agents in the preoperative setting to facilitate surgical resection of locally advanced disease, mostly with a ‘cytoreductive’ (rather than ‘curative’) intent.

In this issue of the BJU Int, Lebacle et al. [2] evaluated the role of neoadjuvant axitinib, an oral tyrosine kinase inhibitor currently recommended as a second‐line option for metastatic clear cell RCC, to downstage cT2 kidney cancer and allow a partial nephrectomy (PN). In this multicentre prospective study, 18 patients with RCC (median tumour size 7.6 cm and R.E.N.A.L. [Radius; Exophytic/Endophytic; Nearness; Anterior/Posterior; Location] score 11) were enrolled. A median tumour size reduction of 17% was obtained, and the primary outcome (‘clinical downstaging’ to cT1 to allow PN) was achieved in 12 patients (67%). Overall, 16 patients underwent PN, as this was successfully done also in four of six (67%) patients who were not ‘down‐staged’ by the drug. Notably, about half of the PNs were performed with a robotic approach. Whilst axitinib was well tolerated, five patients experienced a high‐grade complication after surgery, including one death. Interestingly, final pathology showed upstaging to pT3a disease in seven patients, and two positive margins. Moreover, about a third of patients had metastatic progression and two had recurrence at 2 years. Thus, while the authors noted axitinib to be effective in reducing tumour size and achieving a clinical downstaging in most patients, the significant presence of pT3a disease calls into question the overall efficacy (to truly pathologically downstage) or desirability (most of the tumours that were not downstaged still successfully underwent PN) of the study’s main stated aim.

The rapid adoption of robotic surgery and the increasing experience with PN techniques translated into expanding indications for minimally invasive nephron‐sparing surgery (NSS), to include also T1b and T2 renal masses [3], and the field is primed for a possible paradigm shift. Whether or not a PN is doable, regardless of the technique, remains in the hands of the surgeon, who makes that decision based on previous personal experience. This is also the case for the present study, where the primary outcome was simply represented by the number of patients who could get a PN (instead of a radical nephrectomy). As such, is such a subjective endpoint (feasibility of PN) clinically meaningful? While disagreement may occur over the risk of PN in complex and elective cases, the desirability of nephron preservation in imperative and most elective circumstances is supported by evidence that largely suggests that PN translates into better renal function. In addition, recent findings suggest that estimated GFR preservation might translate into better cancer‐specific survival [4]. Certainly, this type of endpoint (whether a PN is feasible) is prone to intrinsic bias and limitations.

Only a limited number of studies have specifically explored the role of neoadjuvant therapy to enable NSS with variable results [5] (Table 1) [2, 6, 7, 8, 9]. Overall, these studies suggest that even a modest tumour size reduction can facilitate kidney preservation in a significant number of cases. Amongst these studies, only one had assessed axitinib in this specific setting [9]. Differences in outcomes between that trial and the present one by Lebacle et al. [2] could be explained by differences in study populations and/or drug regimens. A more recent study by Karam et al. [10], showed that inter‐observer agreement regarding the feasibility of a PN is quite variable, which is not surprising. For this reason, those authors advocated the need for a ‘resectability score’.

In conclusion, utility of neoadjuvant therapy to modify tumour size and facilitate NSS is an active and exciting area of clinical investigation, fuelled by the rapidly changing landscape of systemic therapies for RCC. It is too early to call for a paradigm shift, but a few ongoing studies might provide some meaningful answers soon. Amongst these, the PADRES (Prior Axitinib as a Determinant of Outcome of REnal Surgery) is an ongoing North American multicentre phase II study of axitinib with the aim of recruiting 50 patients [5]. While waiting for more robust evidence, the use of neoadjuvant therapy to facilitate NSS should still be deemed as investigational.

References

  1. Shuch, BRiggs, SBLaRochelle, JC et al. Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm. BJU Int 2008102692– 6
  2. Lebacle, CBensalah, KBernhard, JC et al. Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study. BJU Int 2019123804– 10
  3. Bertolo, RAutorino, RSimone, G et al. Outcomes of robot‐assisted partial nephrectomy for clinical T2 renal tumors: a multicenter analysis (ROSULA Collaborative Group). Eur Urol 201874:226– 32
  4. Antonelli, AMinervini, ASandri, M et al. Below safety limits, every unit of glomerular filtration rate counts: assessing the relationship between renal function and cancer‐specific mortality in renal cell carcinoma. Eur Urol 201874661– 7
  5. Bindayi, AHamilton, ZAMcDonald, ML et al. Neoadjuvant therapy for localized and locally advanced renal cell carcinoma. Urol Oncol 20183631– 7
  6. Silberstein, JLMillard, FMehrazin, R et al. Feasibility and efficacy of neoadjuvant sunitinib before nephron‐sparing surgery. BJU Int 20101061270– 6
  7. Rini, BIPlimack, ERTakagi, T et al. A phase II study of pazopanib in patients with localized renal cell carcinoma to optimize preservation of renal parenchyma. J Urol 2015194297– 303
  8. Lane, BRDerweesh, IHKim, HL et al. Presurgical sunitinib reduces tumor size and may facilitate partial nephrectomy in patients with renal cell carcinoma. Urol Oncol 201533112.e15–21.
  9. Karam, JADevine, CEUrbauer, DL et al. Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma. Eur Urol 201466874– 80
  10. Karam, JADevine, CEFellman, BM et al. Variability of inter‐observer agreement on feasibility of partial nephrectomy before and after neoadjuvant axitinib for locally advanced renal cell carcinoma (RCC): independent analysis from a phase II trial. BJU Int 2016117629– 35

 

Video: Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Abstract

Objective

To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function.

Patients and Methods

Patients with cT2aN0NxM0 clear‐cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7–10 mg, was administered twice daily, for 2–6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib.

Results

Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5  (70–98) mm and 11 (7–11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III–V post‐surgery complications. At 2‐year follow‐up, six patients had metastatic progression, and two had a recurrence.

Conclusion

Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.

Article of the week: Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathological stage T3a clear‐cell RCC

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathological stage T3a clear‐cell renal cell carcinoma

Paras H. Shah*, Timothy D. Lyon*, Christine M. Lohse, John C. Cheville,
Bradley C. Leibovich*, Stephen A. Boorjian* and R. Houston Thompson*
 
*Department of Urology, Department of Health Sciences Research, and
Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

Abstract

Objective

To investigate the prognostic significance of various patterns of extrarenal extension that comprise pathological stage T3a clear‐cell renal cell carcinoma (ccRCC) amongst patients undergoing nephrectomy for non‐metastatic disease.

Patients and Methods

A retrospective review of 563 patients who underwent radical nephrectomy for pathologically confirmed T3aN0/NxM0 ccRCC between 1970 and 2011 was performed. All pathological slides were re‐reviewed by one urological pathologist. Associations of patterns of extrarenal extension (perinephric fat [PF], renal sinus fat [SF], and renal vein [RV], in isolation or in any combination) with disease progression, cancer‐specific mortality (CSM), and all‐cause mortality were evaluated on multivariable analyses.

Fig. 1. Progression-free survival stratified by type of extrarenal extension

Results

Overall, PF invasion, renal SF invasion, and RV tumour thrombus were present in 144 (26%), 51 (9%), and 163 (29%) patients, respectively, with multiple patterns of extrarenal extension identified in 205 (36%) patients. There were no significant differences in survival outcomes for isolated involvement of PF, renal SF, or RV. However, patients with multiple patterns of extrarenal extension were at significantly increased risk of disease progression (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.04–1.65; P = 0.020), CSM (HR 1.64, 95% CI 1.27–2.12; P < 0.001), and all‐cause mortality (HR 1.32, 95% CI 1.08–1.61; P = 0.008).

Conclusions

The presence of multiple patterns of extrarenal extension is associated with a higher risk of disease progression and cancer‐related death after radical nephrectomy compared to isolated involvement of the PF, renal SF, or RV, which carry similar prognostic weight. If validated, these findings may help refine risk stratification of non‐metastatic T3a RCC by distinguishing patients with multiple vs one pattern of extrarenal extension.

 

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