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

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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

 

Read the full article

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.

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

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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 [2, 3], 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 [4, 5], 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 F, Amparore D, Checcucci 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 ER, Berger LU, Ramachandran 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 2019; 14: 723
  3. Shirk JD, Kwan L, Saigal C. The use of 3‐dimensional, virtual reality models for surgical planning of robotic partial nephrectomy. Urology 2019; 125: 92– 7
  4. Suinesiaputra A, Sanghvi MM, Aung 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 2018; 34: 281
  5. Menze BH, Jakab A, Bauer S et al. The multimodal brain tumor image segmentation benchmark (BRATS). IEEE Trans Med Imaging 2015; 34: 1993– 2024
  6. Smith AD, Lieber ML, Shah SN. Assessing 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 2010; 194: 157– 65
  7. Corradi R, Kabra A, Suarez M et al. Validation of 3‐D volumetric based renal function prediction calculator for nephron sparing surgery. Int Urol Nephrol 2017; 49: 615

 

 

 

 

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

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

Read the full article

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.

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

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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 Albiges, Brigitte 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

 

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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.

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

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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, B, Riggs, SB, LaRochelle, JC et al. Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm. BJU Int 2008; 102: 692– 6
  2. Lebacle, C, Bensalah, K, Bernhard, JC et al. Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study. BJU Int 2019; 123: 804– 10
  3. Bertolo, R, Autorino, R, Simone, G et al. Outcomes of robot‐assisted partial nephrectomy for clinical T2 renal tumors: a multicenter analysis (ROSULA Collaborative Group). Eur Urol 2018; 74:226– 32
  4. Antonelli, A, Minervini, A, Sandri, 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 2018; 74: 661– 7
  5. Bindayi, A, Hamilton, ZA, McDonald, ML et al. Neoadjuvant therapy for localized and locally advanced renal cell carcinoma. Urol Oncol 2018; 36: 31– 7
  6. Silberstein, JL, Millard, F, Mehrazin, R et al. Feasibility and efficacy of neoadjuvant sunitinib before nephron‐sparing surgery. BJU Int 2010; 106: 1270– 6
  7. Rini, BI, Plimack, ER, Takagi, T et al. A phase II study of pazopanib in patients with localized renal cell carcinoma to optimize preservation of renal parenchyma. J Urol 2015; 194: 297– 303
  8. Lane, BR, Derweesh, IH, Kim, HL et al. Presurgical sunitinib reduces tumor size and may facilitate partial nephrectomy in patients with renal cell carcinoma. Urol Oncol 2015; 33: 112.e15–21.
  9. Karam, JA, Devine, CE, Urbauer, DL et al. Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma. Eur Urol 2014; 66: 874– 80
  10. Karam, JA, Devine, CE, Fellman, 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 2016; 117: 629– 35

 

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

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

Read the full article

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.

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EAU19 Barcelona – Highlights from days 3-5 of the 34th Annual EAU Congress

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The early Sunday morning start did not deter delegates from attending one of the three packed plenary sessions of the day. They covered a broad range of rapidly changing areas in urology from imaging in prostate cancer, an update on renal cell carcinoma (RCC) and the breaking news session discussing the potentially game changing results from the recent ARAMIS study and new research into fast bi-parametric MRI.  The role of imaging in prostate cancer is swiftly evolving, with the plenary discussion focusing on recent changes in the diagnostic pathway of localised prostate cancer, particularly with the use of MRI. Next door in the RCC plenary, the speakers debated ‘knife, needle or nothing?’ for the small renal mass in the young patient followed by an update on the very recent and potentially guideline-changing advances in systemic therapy for RCC.

The mid-morning thematic sessions covered the full spectrum of urology from semi-live surgery, the newest advances in immunotherapy, imaging and even how to run a urology office in Europe.

The 7th BJUI social media awards on Sunday night were again the social highlight of the EAU. A view of the Museu Nacional d’Art de Catalunya provided a stunning backdrop to the packed event, with the stars of #UroSoMe recognised for their outstanding work. The night kicked off with the award for the most read blog going to social media champion Professor Declan Murphy.

The awards highlighted the far reaching and valuable impact of social media, recognising a number of important achievements in the field such as Nature Reviews Urology for ‘Both sides of the scalpel: the patient and surgeon view’ with a special guest video appearance from Stephen Fry.

However, for me the most special part of the night was seeing my friend Daniel Christidis remembered and honoured with the most ‘social’ trainee award. Dan was a leader in the real and #UroSoMe world (and had personally set up my Twitter account, and those of many of the other young attendees that night) and I know would have been proud to be remembered for one of the things he did so well.

After the BJUI social media awards, it was time for a little black-tie glamour with the EAU19 Friendship Dinner at the historical Casa Llotja de Mar. The night started with a welcome from Professor Christopher Chapple underlining the importance of international partnerships in urology, followed by a fantastic night of good food, wine and enjoying the beautiful Catalan Gothic architecture.

The Monday morning plenary sessions delivered another jam-packed morning of a mix of cutting-edge science, quality of life issues in cancer survivorship and prostate cancer. The breaking news session discussed the primary results from SAUL, confirming tolerability and safety of atezolizumab in real-world mUC patients, and the results of ARCHES, which investigated the efficacy of androgen deprivation therapy with enzalutamide or placebo in metastatic hormone-sensitive prostate cancer. The controversies in prostate cancer were again debated in an interactive and diverse way between ‘jury members’ including a geriatrician, psychologist, radiation oncologist and urologist.

The last day of the thematic sessions of the congress again provided a smorgasbord of topics in urology. Later in the day, the expert-guided poster tours gave delegates a chance to navigate the huge number of posters from guidelines to local treatment of prostate cancer.

The closing plenary on Tuesday morning to a full auditorium gave a sweeping overview of the top contributions to EAU19 leaving us with a free half day to explore our generous host city and take in the stunning architecture, food and sunshine!

 

Bustling Barcelona provided the perfect backdrop to a well organised, action packed conference which featured world leading urologists and scientists from around the world presenting practice changing new data. Cannot wait for EAU 2020 in Amsterdam! #EAU20 #Amsterdam #UroSoMe

by Jiasian Teh, Urology Registrar, PhD Candidate, Peter MacCallum Cancer Centre

@JiasianTeh

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

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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
 

 

Read the full article

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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Editorial: Does knowing the risk of relapse in localized renal cell carcinoma matter?

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Shah et al. [1] report a retrospective analysis from the Mayo Clinic investigating the prognostic significance of different patterns of pathological T3a clear‐cell RCC in patients who underwent radical nephrectomy for localized disease. There was no difference in disease progression, cancer‐specific mortality or all‐cause mortality when comparing isolated perinephric fat invasion vs isolated renal sinus fat invasion vs isolated renal vein invasion. Multiple sites of extra‐renal extension compared with one site, however, was independently associated with an increased risk of disease progression (hazard ratio [HR] 1.31, P = 0.02), death from RCC (HR 1.64, P < 0.001) and all‐cause mortality (HR 1.32, P = 0.008) when adjusting for multiple key variables including age, tumour size, grade, presence of coagulative tumour necrosis and sarcomatoid differentiation. The authors incorporated multiple sites of extra‐renal extension vs one site into three RCC prognostic models: SSIGN score, UISS and MSKCC nomogram. After controlling for these three predictive tools independently, multiple sites of extra‐renal disease predicted progression, death from RCC and all‐cause death. These data suggest that risk stratification for pT3aN0MO clear‐cell RCC is improved by differentiating multiple vs one site of extra‐renal extension.

Does an improved ability to predict recurrence and mortality increase the likelihood of cure in high‐risk localized RCC patients in 2018? Unfortunately, the answer is no. Ideally, prognostic models would identify patients at sufficient risk to consider adjuvant therapy, which would increase cure rates by eradicating micro‐metastatic disease with an acceptable toxicity. Regrettably, in RCC management there are no well‐established post‐surgical therapies that improve cure rates. The deficiency of established adjuvant therapies is not attributable to a lack of investigative trials. In the era before vascular endothelial growth factor receptor (VEGFR) targeting, adjuvant vaccines, immunotherapies and other systemic therapies failed to demonstrate improved recurrence‐free (RFS) or overall survival (OS) [2]. The efficacy of VEGFR‐targeted therapies in the metastatic setting re‐energized the hope for adjuvant therapy in patients with high‐risk localized RCC after surgical resection in the past two decades. The results to date have been disappointing. To date, three trials (ASSURE, PROTECT and S‐TRAC) have been completed, comparing oral VEGFR tyrosine kinase inhibitors with placebo in high‐risk localized clear‐cell RCC, with disease‐free survival (DFS) as the primary endpoint [3,4,5]. ASSURE and PROTECT showed no difference in RFS or OS [3,4,5]. S‐TRACT demonstrated an improvement in DFS but not in OS [4]. A pooled analysis of these three trials also failed to demonstrate improved DFS or OS with adjuvant VEGFR‐targeted therapy [6]. Significant side effects with discontinuation of adjuvant therapy occurred in 28–45% of patients as a result of drug‐related toxicity [6]. Trials investigating immune checkpoint inhibitors have yet to be published and, with the established efficacy of these drugs in the metastatic setting, hope still remains for adjuvant therapy in resected high‐risk localized RCC.

If the current literature does not support adjuvant therapy for resected high‐risk RCC, does knowing the risk of relapse alter surveillance? National Comprehensive Cancer Network guidelines for resected stage III RCC recommend chest and abdominal imaging within 3–6 months, along with subsequent chest and abdominal imaging every 3–6 months for 3 years, and then annually up to 5 years. Although the ideal schedule for surveillance imaging is unknown, further characterizing of the risk of relapse in high‐risk localized RCC would not be likely to affect this schedule significantly.

Although knowing the risk of relapse in high‐risk localized RCC does not help management in 2018, there is still a value to enhancing our prognostic tools. For one, our prognostic tools help clinicians counsel patients appropriately about their risk of recurrence. In addition, enhanced prognostic tools will assist in selecting appropriate patients with high‐risk localized RCC for future clinical trials of adjuvant therapy and also help us understand the results when comparing cohorts within and between trials.

References

  1. Shah PH, Lyon TD, Lohse CM. Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathologic stage T3a clear cell renal cell carcinoma. BJU Int 2019; 123: 270–6
  2. Scherr AJO, Lima JPSN, Sasse EC et al. Adjuvant therapy for locally advanced renal cell cancer: a systematic review with meta‐analysis. BMC Cancer 2011; 11: 115–21
  3. Haas N, Manola J, Uzzo R et al. Adjuvant sunitinib or sorafenib for high‐risk, non‐metastatic renal‐cell carcinoma (ECOG‐ACRIN E2805): a double‐blind, placebo‐controlled, randomised, phase 3 trial. Lancet 2016; 387: 2008–16
  4. Ravaud A, Motzer RJ, Pandha HS et al. Adjuvant sunitinib in high‐ risk renal‐cell carcinoma after nephrectomy. N Engl J Med 2016; 375: 2246–54
  5. Motzer RJ, Haas NB, Donskov F et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma. J Clin Oncol 2017; 35: 3916–23
  6. Sun M, Marconi L, Eisen T et al. Adjuvant vascular endothelial growth factore‐targeted therapy in renal cell carcinoma. Eur Urol 2018; 74: 611–20

 

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