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Editorial: Nationwide prostatectomy practice

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Surgical management of prostate cancer is one of the most frequently performed urological procedures [1]. Available data suggests that surgeons’ experience is correlated with both oncological and functional outcome [2]. These initial observations stress the importance of concentration of prostatectomy in high-volume institutes. This centralisation could improve documentation and monitoring of outcome. The data presented by Røder et al. [1] from Denmark show a rapid increase in registered prostatectomy procedures in recent years in six institutes. It remains to be studied whether this is caused by centralisation and better registration or the results of an increased overtreatment. For that, data on the incidence of low-risk disease over time in their series needs analysis.

At least one-third of the population was treated since 2008. The relatively short follow-up and associated few events, and high number of low-risk patients (47% had biopsy Gleason ≤6) make outcome analysis of less value. It is therefore not surprising that in their analysis low- and intermediate-risk tumors had similar outcome. On the other hand, despite prostatectomy, one-third of deaths during follow-up were prostate cancer related in their population. Consistent with reported data at 15 years after prostatectomy more patients died from prostate cancer than from other causes [3]. But still a considerable number of men died from prostate cancer. This also seems the case in the group of men often soothed for having indolent, low-risk disease. At 15 years Røder et al., reported 8.9% of these men with low-risk disease still dying from prostate cancer in Denmark, despite prostatectomy. And although this percentage was lower than that of the prostatectomy group in the Scandinavian Prostate Cancer Group Study Number 4 (SCPG-4) study (14.6%) [4], most men will still find it disturbingly high and it is three-times higher than the 3% life-time risk of dying from prostate cancer for all men. In other words, it may be perceived that prostatectomy does only partly reverse the risk of dying from prostate cancer, even in men with low-risk disease.

The data from Røder et al. [1] can, with longer follow-up, set the standard for oncological outcome on a national level. Of interest is the observation that, although not significant in the multivariate analysis, variation among institutes for outcome seems to exist but not clearly dependent on institutes volume. Variations of case-mix and patient selection could be topics of further study. With the short follow-up available we are also looking forward to data on functional outcome and perioperative complications that may be more mature. Comparison with now also available registries in Belgium and the Netherlands would be of interest.

It always strikes me that prostate cancer seems to be a systemic disease from the start even in assumed ‘low-risk’ disease, yet surgical management is only focused at loco-regional control. Perhaps the mortality improvement shown in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial by prostatectomy is merely caused by disease delay provided by local control even in the presence of systemic disease. Initial encouraging data from an ongoing study evaluating the role of radiotherapy to the prostate in the presence of bone metastases seem supportive of this notion. Is prostatectomy a debulking management of a systemic disease at most, and an unneeded cure for many, or is there this sub-sub group of men that is eventually fully benefiting from the intervention reversing not only death but also the debilitating effects of androgen ablation.

Henk G. van der Poel
Department of Urology, Netherlands Cancer Institute, Amsterdam, the Netherlands
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References

  1. Røder MA, Brasso K, Christensen IB et al. Survival after radical prostatectomy for clinically localised prostate cancer: a population-based study. BJU Int 2014; 113: 541–547
  2. Vickers A, Savage C, Bianco F et al. Cancer control and functional outcomes after radical prostatectomy as markers of surgical quality: analysis of heterogeneity between surgeons at a single cancer center. Eur Urol 2011; 59: 317–322
  3. Shikanov S, Kocherginsky M, Shalhav AL, Eggener SE. Cause-specific mortality following radical prostatectomy. Prostate Cancer Prostatic Dis 2012; 15: 106–110
  4. Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708–1717

 

Video: Survival after RP for clinically localised prostate cancer

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Survival after radical prostatectomy for clinically localised prostate cancer: a population-based study

Martin Andreas Røder1, Klaus Brasso1, Ib Jarle Christensen2, Jørgen Johansen3, Niels Christian Langkilde4, Helle Hvarness1, Steen Carlsson5, Henrik Jakobsen6, Michael Borre7 and Peter Iversen1

1Copenhagen Prostate Cancer Center and Department of Urology, 2The Finsen Laboratory, Copenhagen Biotech Research and Innovation Centre (BRIC), Rigshospitalet Copenhagen University Hospital, Faculty of Health and Medical Sciences, Copenhagen, 3Department of Urology, Regional Hospital West Jutland, Holstebro, 4Department of Urology, Aalborg University Hospital, Faculty of Medicine, Aalborg, 5Department of Urology, Odense University Hospital, Faculty of Health Sciences, Odense, 6Department of Urology, Herlev Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, Herlev and 7Department of Urology, Skejby, Aarhus University Hospital, Department of Clinical Medicine, Aarhus, Denmark

 

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OBJECTIVES

• To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP).

• To describe risk factors associated with prostate cancer mortality.

PATIENTS AND METHODS

• Observational study of 6489 men with localised prostate cancer treated with RP at six different hospitals in Denmark between 1995 and 2011.

• Survival was described using Kaplan–Meier estimates. Causes of death were obtained from the national registry and cross-checked with patient files.

• Cumulative incidence of death, any cause and prostate cancer-specific, was described using Nelson–Aalen estimates.

• Risk for prostate cancer death was analysed in a Cox multivariate regression model using the covariates: age, cT-category, PSA level and biopsy Gleason score.

RESULTS

• The median follow-up was 4 years. During follow-up, 328 patients died, 109 (33.2%) from prostate cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP.

• In multivariate analysis, cT-category was a predictor of prostate cancer death (P < 0.001). Compared with T1 disease, both cT2c (hazard ratio [HR] 2.2) and cT3 (HR 7.2) significantly increased the risk of prostate cancer death. For every doubling of PSA level the risk of prostate cancer death was increased by 34.8% (P < 0.001). Biopsy Gleason score 4 + 3 and ≥8 were associated with an increased risk of prostate cancer death compared with biopsy Gleason score ≤ 6 of 2.3 and 2.7 (P = 0.003), respectively.

• The cumulative hazard of all-cause and prostate cancer-specific mortality after 10 years was 15.4% (95% confidence interval [CI] 13.2–17.7) and 6.6% (95% CI 4.9–8.2) respectively.

CONCLUSIONS

• We present the first survival analysis of a complete, nationwide cohort of men undergoing RP for localised prostate cancer.

• The main limitation of the study was the relatively short follow-up.

• Interestingly, our national results are comparable to high-volume, single institution, single surgeon series.

 

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Article of the month: The surgical spectacle

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Every week the Editor-in-Chief selects the 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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

The surgical spectacle: a survey of urologists viewing live case demonstrations

Sammy E. Elsamra, Mathew Fakhoury, Hector Motato, Justin I. Friedlander, Daniel M. Moreira, Joel Hillelsohn, Brian Duty, Zeph Okeke and Arthur D. Smith

The Arthur Smith Institute for Urology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY, USA

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OBJECTIVE

• To evaluate perspectives of urologists viewing live case demonstrations (LCD) and taped case demonstrations (TCD).

METHOD

• A 15-question anonymous survey was distributed to attendees of the live surgery session at the American Urological Association 2012 national meeting (Atlanta) and the second International Challenges in Endourology meeting (Paris).

RESULTS

• Of 1000 surveys distributed, 253 were returned completed (response rate 25%). Nearly half of respondents were in the academic practice setting and nearly 75% were beyond training.

• Just over 30% had performed a LCD previously. The perceived benefit of an LCD was greater than unedited and edited videos (chi-squared P = 0.014 and P < 0.001, respectively). Nearly no one selected ‘not helpful’ and a few selected ‘minimally helpful’ for any of the three forms of demonstration.

• Most respondents identified that opportunity to ask questions (61%) and having access to the full unedited version (72%), two features inherent to LCD, improved upon the educational benefit of edited videos.

• Most (78%) identified LCD as ethical. However, those that did not perceived lower educational benefit from LCD (P = 0.019).

• A slim majority (58%) would allow themselves or a family member to be a patient of a LCD and the vast majority (86%) plan to transfer knowledge gained at the LCD session into their practice.

CONCLUSIONS

• Urologists who attended these LCD sessions identified LCDs as beneficial and applicable to their practice.

• LCDs are preferred over videos. The large majority considers LCD ethical, although not as many would volunteer themselves for LCD.

• Further studies are necessary to determine if there is actual benefit from LCD over TCD to patient care.

 

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Editorial: Do live case demonstrations have a future in surgical education?

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The ever increasing desire for instant access to information is a reflection of our times facilitated by social networks and by video and information technology. Nowadays, sport events are dissected and quantified from every possible perspective. We know almost real-time any detail of a soccer match: how many miles each player runs, how many good or bad passages of play, how many faults and so on, including if needed the details of heart rate and weight loss. The same and even more is available for example in formula one racing. Theoretically the same could easily be applied to surgical performance and it is foreseeable it will be applied, as a self-performance improvement method and as a development of one of the most popular ‘scientific and educational’ activities during surgical meetings, live case demonstrations (LCDs). All this, together with simulation, could in the near future have a tremendous impact on surgical performance and training. Twitter and Instagram show the power of the immediate real-time diffusion of events, as condensed as possible, so that the tweet or the instantaneous image can be visible and digested without losing time. Video clips follow the same concept and certainly BJUI is pioneering the use of short surgical video clips that are easily accessible and usable at any spare time of a busy day.

The core issue about LCDs is that at present there is no solid scientific evidence of their educational value, and this is outlined in the paper by Elsamra et al. [1] published in this issue of BJUI, which commendably attempts to evaluate the educational benefit of LCDs in terms of perception, clearly not a very strong criterion.

Data about the outcomes of live surgery operations are scant. Clearly patient’s safety is the first goal of any surgical activity, and this applies to LCDs. As mentioned in the paper, the European Association of Urology (EAU) Executive felt the urgent need to establish procedures and regulations in order to endorse live surgery events. The reader can find all related information on the EAU website. These regulations are meant to be in the best interest of patients, surgeons and organisers. Among others, one important innovation is the requisite of a ‘patient advocate’ present during the LCD, being an experienced medical doctor, independent from the organising committee of the educational event, in charge of advising in case of unexpected events, which can endanger patient’s safety.

Moreover, the EAU has established a prospective database of all endorsed live surgery events. This will hopefully allow in a few years an answer, with solid data, to the question of whether an intervention performed during a live surgery event has the same outcome compared with the same intervention executed by the same surgeon in his usual environment. The more challenging goal is to quantify the educational value of a live surgical event and the jump from perception to scientific evidence is far from being an easy task.

Walter Artibani
Urologia – Azienda Ospedaliero Universitaria Integrata di Verona, Verona, Italy

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Reference

  1. Elsamra SE, Fakhoury M, Motato H et al. The surgical spectacle: a survey of urologists viewing live case demonstrations. BJU Int 2014; 113: 674–678
 

Article of the week: Impact of blood transfusion during radical cystectomy

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Every week the Editor-in-Chief selects the 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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Kluth discussing his paper.

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

Impact of peri-operative blood transfusion on the outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder

Luis A. Kluth1,3, Evanguelos Xylinas1,4, Malte Rieken1,5, Maya El Ghouayel1, Maxine Sun1, Pierre I. Karakiewicz6, Yair Lotan7, Felix K.-H. Chun3, Stephen A. Boorjian8, Richard K. Lee1, Alberto Briganti9 , Morgan Rouprêt10, Margit Fisch3, Douglas S. Scherr1 and Shahrokh F. Shariat1,2,11

1Department of Urology and 2Division of Medical Oncology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA, 3Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, 4Department of Urology, Cochin Hospital, Assistance Publique-Hopitaux de Paris, Paris Descartes University, Paris, France, 5Department of Urology, University Hospital of Basel, Basel, Switzerland, 6Department of Urology, University of Montreal, Montreal, QC, Canada, 7Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA, 8Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, MN, USA, 9Department of Urology, Vita-Salute University, Milan, Italy, 10Department of Urology of la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, University Paris VI, Faculté de Médicine Pierre et Marie Curie, Paris, France, and 11Department of Urology, Medical University of Vienna, Vienna, Austria

L.A.K. and E.X. contributed equally to this work

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OBJECTIVE

• To determine the association between peri-operative blood transfusion (PBT) and oncological outcomes in a large multi-institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

PATIENTS AND METHODS

• We conducted a retrospective analysis of 2895 patients treated with RC for UCB.

• Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer-specific mortality, and any-cause mortality.

RESULTS

• Patients’ median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow-up was 36.1 (15, 84) months.

• Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004).

• PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer-specific mortality (P = 0.017), and any-cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05).

• In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer-specific mortality and any-cause mortality (all P values <0.002).

CONCLUSIONS

• Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer-specific mortality and any-cause mortality in univariable, but not multivariable, analysis.

• Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer-related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.

 

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Editorial: Radical cystectomy: how do blood transfusions affect oncological outcomes?

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Kluth et al. [1] have conducted a large retrospective study from several institutions in North America and Europe to assess the impact of blood transfusion on oncological outcomes after radical cystectomy (RC) for bladder cancer. The hypothesis for a negative impact of transfusion on oncological outcomes stems from the observation that renal allograft survival is prolonged after pre-transplant blood transfusions because of its immuno-modulatory effects [2]. This finding prompted Gantt [3] to express concern about the possible adverse effects of transfusions in patients being treated for cancer. Since then, there have been numerous publications addressing this issue in various surgical journals including those of urology with conflicting messages.

Sadeghi et al. [4] queried the Columbia University Urologic Oncology Database. This included 638 patients undergoing RC between 1989 and 2010. Of these, 209 (32.8%) received perioperative blood transfusions. On univariate analysis, the number of units transfused was inversely related to overall and cancer-specific survival. However, on multivariate analysis, it did not prove to be an independent predictor of cancer-specific survival.

As the authors highlighted in this paper, Linder et al. [5] reported a large series of patients from the Mayo Clinic, which included 2060 patients undergoing RC over 25 years. Of this large cohort, 1279 (62%) received perioperative blood transfusion with adverse outcomes, not only in terms of overall and cancer-specific mortality, but also postoperative tumour recurrence.

RC is one of the most major surgical procedures performed in urological surgery. The vast majority of patients with bladder cancer requiring RC are in their mid-sixties, overweight and have several co-morbidities. Some of these patients present late and are anaemic at presentation.

Blood loss during open RC varies depending upon surgeons’ experience, patients’ body mass index, disease stage and availability of modern equipment, e.g. LigaSure™ or stapling devices. Blood transfusion may be required because of pre-existing anaemia or excessive blood loss during surgery. Variations exist in thresholds of anaesthesiologists and the surgeons for transfusions. All of these factors account for variation in reported frequency of transfusion rates for this operation and this is well reflected in many large series of RC.

As there are many confounding factors that may influence overall and cancer-specific survival in patients undergoing RC including stage of the disease, histological nature of the tumour, lymph node status and competing co-morbidities, it is very challenging to control for these factors in retrospective series. Hence, prospective well-controlled multicentre studies are the only way forward to answer this question.

While we await robust evidence on the influence of perioperative transfusion on oncological outcomes, several potential options could be explored to avoid homologous blood transfusion. These include preoperative optimisation of haemoglobin levels through iron infusions, administration of erythropoietin where appropriate, and preoperative autologous-banking. Intraoperatively meticulous surgical technique, use of modern devices, e.g. LigaSure/stapler and Cell Savers, could be used to avoid homologous blood transfusion.

Fortunately, these studies aimed at raising awareness of potential risks of transfusions are appearing in the urological literature at a time when urologists are moving away from open to minimally invasive oncological surgery with a steady decline in the need for perioperative blood transfusion. This is one of the important steps in the right direction and will have a major impact on the need for blood transfusion in foreseeable future.

Muhammed S. Khan
Department of Urology, Guy’s Hospital and King’s College London School of Medicine, London, UK

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References

  1. Kluth LA, Xylinas E, Rieken M et al. Impact of perioperative blood transfusion on the outcome of patients undergoing radical cystectomy for urothelial carcinoma of the bladder. BJU Int 2014; 113: 393–398
  2. Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973; 5: 253–259
  3. Gantt CL. Red blood cells for cancer patients. Lancet 1981; 2: 363
  4. Sadeghi N, Badalato GM, Hruby G, Kates M, McKiernan JM. The impact of perioperative blood transfusion on survival following radical cystectomy for urothelial carcinoma. Can J Urol 2012; 19: 6443–6449
  5. Linder BJ, Frank I, Cheville JC et al. The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013; 63: 839–845
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Article of the week: Pneumonitis should not prevent continued mTOR inhibitor use

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Every week the Editor-in-Chief selects the 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 accompanying editorial written by prominent members of the urological community. This blog is 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.

Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes

Bradley J. Atkinson, Diana H. Cauley, Chaan Ng*, Randall E. Millikan†, Lianchun Xiao‡, Paul Corn†, Eric Jonasch† and Nizar M. Tannir†

Departments of Pharmacy Clinical Programs, *Diagnostic Radiology, †Genitourinary Medical Oncology and ‡Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA

B.J.A. and D.H.C. are co-first authors
Supported in part by a Cancer Center Support Grant (CA016672) from the National Institutes of Health.

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OBJECTIVE

• To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC).

PATIENTS AND METHODS

• Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010.

• Clinical correlations were made with serial radiological imaging.

• Fisher’s exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors.

• Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis.

RESULTS

• NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively).

• The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups.

• Older age and everolimus treatment were predictive of NIP.

• Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months).

• NIP was a predictor of improved OS by multivariate analysis.

CONCLUSIONS

• There was an increased incidence of NIP in everolimus-treated patients.

• Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.

 

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Editorial: mTOR-related non-infectious pneumonitis: a potential biomarker of clinical benefit?

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The study by Atkinson et al. [1] published in the present issue of the BJUI is the largest study to date to address the role of non-infectious pneumonitis (NIP) as a predictive biomarker in patients with RCC who are treated with mammalian target of rapamycin (mTOR) inhibitors. It is also the first article to correlate mTOR-related NIP with improved overall survival (OS). Until now, only radiological response as measured by RECIST and progression-free survival (PFS) had been correlated to the onset of NIP in two small retrospective studies [2, 3], but the results obtained in those studies were contradictory and, therefore, this correlation remains controversial.

While the predictive relationship between NIP and OS needs to be further investigated in well-designed prospective clinical trials, the implications of such a relationship may be significant because no predictive biomarkers for mTOR inhibitors have been validated to date. In the era of targeted therapies, the detection of biomarkers of treatment efficacy is crucial to differentiate the subpopulations of patients who are most likely to benefit from treatment. Several biomarkers, such as the development of arterial hypertension and hypothyroidism, have been correlated with improved outcomes in patients with advanced RCC treated with vascular endothelial growth factor pathway inhibitors [1]; however, there are currently very limited data regarding the potential predictors of the clinical efficacy of mTOR inhibitors. A recent study by Lee et al. [4] showed that greater increases in serum cholesterol levels from baseline in patients with advanced RCC treated with temsirolimus were significantly associated with longer PFS and OS. Interestingly, temsirolimus-related hypertriglyceridemia and hyperglycaemia were not associated with improved clinical outcomes. Although NIP or hypercholesterolaemia must still be validated prospectively to ascertain whether they are true surrogate biomarkers of pharmacodynamic effect or just confounding epiphenomena, these promising findings may be the first steps in the identification of predictive biomarkers in mTOR inhibitor therapy.

Other important aspects addressed by Atkinson et al. [1] are the uncertainty of the pathogenesis of mTOR-related NIP and the lack of clinical predictive factors. Older age and treatment with everolimus were the only significant predictive factors of onset of NIP in their multivariate analysis. Similarly, a retrospective study by Dabydeen et al. [2] showed a statistically nonsignificant higher incidence of NIP in patients with RCC treated with everolimus compared to those treated with temsirolimus. Interestingly, in a randomized phase II study testing three different dose levels of temsirolimus (25,75 and 250 mg/week) in patients with advanced RCC, none of the six patients diagnosed with NIP were in the highest dose group of 250 mg/week [5], suggesting that mTOR-related NIP might have a non-dose-dependent pathogenesis. Similarly, a meta-analysis of 2233 patients affected by different tumours including RCC treated with an mTOR inhibitor failed to show any relationship between median treatment duration and incidence of NIP [6]. Finally, underlying respiratory conditions before treatment, such as the presence of lung metastases [6], chronic obstructive pulmonary disease or smoking habit [2], were not shown to be predictive factors of development of mTOR-related NIP. Another study by White et al. [3] showed that the development of pneumonitis in patients with RCC treated with everolimus was not associated with more impaired baseline pulmonary function tests, indicating that pulmonary function tests may not help identify patients with an increased risk of pneumonitis nor predict its severity. At present, there are therefore very few pretreatment clinical predictive factors to help clinicians identify patients at higher risk of developing mTOR-related NIP.

In conclusion, given the potential value of NIP as a predictive biomarker of survival in patients with RCC treated with mTOR inhibitors, Atkinson et al. [1] suggest that efforts should be made to avoid dose reductions and treatment discontinuation whenever possible. However, predictive factors of the severity of lung toxicity are needed to identify those patients at risk of developing life-threatening NIP as the maintenance of dose intensity may be crucial for maximizing clinical benefit.

Read the full article

Alejo Rodriguez-Vida, Noan-Minh Chau and Simon Chowdhury
Department of Medical Oncology, Guy’s Hospital, London, UK

References

  1. Atkinson BJ, Pharm D, Cauley DH et al. mTOR inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: management, predictors, and outcomes. BJU Int 2014; 113: 376–382
  2. Dabydeen DA, Jagannathan JP, Ramaiya N et al. Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: incidence, radiographic findings and correlation with clinical outcome. Eur J Cancer 2012; 48:1519–1524
  3. White DA, Camus P, Endo M et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 2010; 182: 396–403
  4. Lee CK, Marschner IC, Simes RJ et al. Increase in cholesterol predicts survival advantage in renal cell carcinoma patients treated with temsirolimus. Clin Cancer Res 2012; 18: 3188–3196
  5. Atkins MB, Hidalgo M, Stadler WM et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004; 22: 909–918
  6. Iacovelli R, Palazzo A, Mezi S, Morano F, Naso G, Cortesi E. Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials. Acta Oncol 2012; 51: 873–879

 

Article of the week: Restored renal function after RN

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Every week the Editor-in-Chief selects the 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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Chung discussing his paper.

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

Trends in renal function after radical nephrectomy: a multicentre analysis

Jae S. Chung1, Nak H. Son2, Seok-Soo Byun6, Sang E. Lee6, Sung K. Hong6, Chang W. Jeong6, Sang C. Lee6, Dong-Wan Chae7, Won S. Choi8, Yong H. Park3, Sung H. Hong4, Yong J. Kim9 and Seok H. Kang5

1Department of Urology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, 2Department of Biostatistics, Yonsei University College of Medicine, 3Department of Urology, Seoul National University Hospital, 4Department of Urology, Seoul St. Mary’s Hospital, 5Department of Urology, Korea University Anam Hospital, Seoul, 6Departments of Urology and 7Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 8Choi Won Suk Urology Clinic, Yongin, and 9Department of Urology, Chungbuk National University Hospital, Cheongju, Korea

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OBJECTIVE

• To evaluate serial changes in renal function by investigating various clinical factors after radical nephrectomy (RN).

PATIENTS AND METHODS

• The study population consisted of 2068 consecutive patients who were treated at multiple institutions by RN for renal cortical tumour without metastasis between 1999 and 2011.

• We measured the serial change in estimated glomerular filtration rate (eGFR) and clinical factors during a 60-month follow-up period.

• The changes in eGFR over time were analysed according to baseline eGFR (eGFR ≥60 and 15–59 mL/min/1.73m2) using a linear mixed model.

• The independent prognostic value of various clinical factors on the increase in eGFR was ascertained by multivariate mixed regression model.

RESULTS

• Overall, there was a subsequent restoration of renal function over the 60 months.

• The slope for the relationship between the eGFR and the time since RN was 0.082 (95% confidence interval [CI] 0.039–0.104; P < 0.001) and 0.053 (95% CI 0.006–0.100; P = 0.038) in each baseline group, indicating that each month after RN was associated with an increase in eGFR of 0.082 and 0.053 mL/min/1.73m2, respectively.

• When we analysed renal function based on various factors, postoperative eGFR of patients with diabetes mellitus, old age (≥70 years) or a preoperative eGFR of <30 mL/min/1.73 m2, was decreased or maintained at a certain level without any improvement in renal function.

• Preoperative predictors of an increase in eGFR after RN were young age, no DM, no hypertension, a preoperative eGFR of ≥30 mL/min/1.73m2 and time after surgery (≥36 months).

CONCLUSIONS

• Renal function recovered continuously during the 60-month follow-up period after RN.

• However, the trends in functional recovery change were different according to various clinical factors and such information should be discussed with patients when being counselled about their treatment for renal cell carcinoma (RCC).

 

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Editorial: Renal functional recovery after radical nephrectomy

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In their publication ‘Trends in renal function after radical nephrectomy: a multicentre analysis’, Chung et al. [1] suggest that after radical nephrectomy (RN), renal functional recovery in patients who have RCC occurs even in states of baseline renal functional compromise (pre-existing stage III chronic kidney disease, CKD). These findings bolster other recent reports, which suggest that surgically induced CKD may not be associated with the same degree of renal functional decline as CKD that may be caused by medical factors [2, 3]. While the incidence of de novo stage III CKD (36.1%) and delta estimated GFR between preoperative and postoperative values are lower than reported by most other groups, which may be attributable to national and demographic trends that are different from North American and European trends [2-4], the findings are nonetheless important and show that in the short-to-intermediate term (median follow up of 33 months) continued renal functional stabilisation and recovery occurs after RN. Also, performing a RN in a patient does not sentence him or her to invariable or inevitable renal functional decline in the short-to-intermediate term. Furthermore, they establish, in the short-to-intermediate term at least, a reasonable timeline of renal functional recovery for patient counselling and physician expectations in the postoperative follow-up period. Interestingly, and perhaps more disturbingly, the authors noted minimal and no functional recovery in the elderly and diabetic groups, underlying the importance for consideration of nephron-sparing approaches in these higher risk subgroups, even in the setting of normal renal function, and particularly with a lower risk lesion, e.g. a clinical T1a renal mass [5]. What we are missing from this analysis are longer term data, and a more thorough analysis of the incidence and impact of potential metabolic and cardiovascular sequelae during this period [4, 6], and a comparative analysis that examines the timeline of renal functional recovery after partial nephrectomy. Because of these reasons, the reader should be cautioned not to over-interpret these findings, and to conclude that because RN is associated with renal functional recovery, performing a RN may not pose increased long-term risk compared with a nephron-sparing method, particularly in a patient with pre-existing medical drivers towards CKD (diabetes, obesity, hyperlipidaemia, etc.). These findings are nonetheless important and provocative, and should spur further investigation and may provide an important adjunct in the counselling of patients about the functional impact of RN.

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Ithaar H. Derweesh
Department of Urology, University of California San Diego Health System, La Jolla, CA, USA

References

  1. Chung JS, Son NH, Byun SS et al. Trends in renal function after radical nephrectomy: a multicentre analysis. BJU Int 2014; 113:408–415
  2. Van Poppel H, Da Pozzo L, Albrecht W et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011; 59:543–552
  3. Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 2013; 189: 1649–1655
  4. Sun M, Bianchi M, Hansen J et al. Chronic kidney disease after nephrectomy in patients with small renal masses: a retrospective observational analysis. Eur Urol 2012; 62: 696–703
  5. Campbell SC, Novick AC, Belldegrun A et al. Guideline for management of the clinical T1 renal mass. J Urol 2009; 182:1271–1279
  6. Woldrich J, Mehrazin R, Bazzi WM et al. Comparison of rates and risk factors for development of anaemia and erythropoiesis-stimulating agent utilization after radical or partial nephrectomy. BJU Int 2012; 109: 1019–1025

 

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