Tag: renal cell carcinoma

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Video: Be Clear on Cancer – Blood in Pee

April 6, 2016/by admin Z.9

Assessing the impact of mass media public health campaigns. ‘Be Clear on Cancer: Blood in Pee’ a case in point

Archie Hughes-Hallett*, Daisy Browne†, Elsie Mensah*, Justin Vale*† and Erik Mayer*†‡

*Department of Surgery and Cancer, Imperial College London, †Department of Urology, Imperial College Healthcare Trust, and ‡Institute of Global Health Innovation, Imperial College London, London, UK

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Objectives

To assess the impact on suspected cancer referral burden and new cancer diagnosis of Public Health England’s recent Be Clear on Cancer ‘blood in pee’ mass media campaign.

Methods

A retrospective cohort study design was used. For two distinct time periods, August 2012 to May 2013 and August 2013 to May 2014, all referrals of patients deemed to be at risk of urological cancer by the referring primary healthcare physician to Imperial College NHS Healthcare Trust were screened. Data were collected on age and sex and whether the referral was for visible haematuria, non-visible haematuria or other suspected urological cancer. In addition to referral data, hospital episode data for all new renal cell (RCC) and upper and lower tract transitional cell carcinoma (TCC), as well as testicular and prostate cancer diagnoses for the same time periods were obtained.

Results

Over the campaign period and the subsequent 3 months, the number of haematuria referrals increased by 92% (P = 0.013) when compared with the same period a year earlier. This increase in referrals was not associated with a significant corresponding rise in cancer diagnosis; instead changes of 26.8% (P = 0.56) and −3.3% (P = 0.84) were seen in RCC and TCC, respectively.

Conclusions

This study has shown that the Be Clear on Cancer ‘blood in pee’ mass media campaign significantly increased the number of new suspected cancer referrals, but there was no significant change in the diagnosis of target cancers across a large catchment. Mass media campaigns are expensive, require significant planning and appropriate implementation and, while the findings of this study do not challenge their fundamental objective, more work needs to be done to understand why no significant change in target cancers was observed. Further consideration should also be given to the increased referral burden that results from these campaigns, such that pre-emptive strategies, including educational and process mapping, across primary and secondary care can be implemented.

Guideline of guidelines: follow-up after nephrectomy for renal cell carcinoma

March 9, 2016/by admin Z.9

Abstract

The purpose of this article was to review and compare the international guidelines and surveillance protocols for post-nephrectomy renal cell carcinoma (RCC). PubMed database searches were conducted, according to the PRISMA statement for reporting systematic reviews, to identify current international surveillance guidelines and surveillance protocols for surgically treated and clinically localized RCC. A total of 17 articles were reviewed. These included three articles on urological guidelines, three on oncological guidelines and 11 on proposed strategies. Guidelines and strategies varied significantly in relation to follow-up, specifically with regard to the frequency and timing of radiological imaging. Although there is currently no consensus within the literature regarding surveillance protocols, various guidelines and strategies have been developed using both patient and tumour characteristics.

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Article of the week: Pneumonitis should not prevent continued mTOR inhibitor use

March 19, 2014/by admin Z.9

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.

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

March 19, 2014/by Simon Chowdhury

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.

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

References

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
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
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
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
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
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: SEER shows no benefit from LND in RCC

January 15, 2014/by admin Z.9

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 Maxine Sun discussing her paper.

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

Extent of lymphadenectomy does not improve the survival of patients with renal cell carcinoma and nodal metastases: biases associated with the handling of missing data

Maxine Sun*, Quoc-Dien Trinh*^‡, Marco Bianchi*^¶, Jens Hansen*^††, Firas Abdollah^¶, Zhe Tian*, Shahrokh F. Shariat^§, Francesco Montorsi^¶, Paul Perrotte^† and Pierre I. Karakiewicz*^†

*Cancer Prognostics and Health Outcomes Unit, ^†Department of Urology, University of Montreal Health Center, Montreal, Canada, ^‡Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, ^§Department of Urology,Weill Medical College of Cornell University, New York, NY, USA, ^¶Department of Urology, Vita-Salute San Raffaele University, Milan, Italy, and ^††Martini Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany

Maxine Sun and Quoc-Dien Trinh contributed equally to this study.

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OBJECTIVE

• Previous studies showed no survival benefit with respect to performing lymph node dissection (LND) at nephrectomy, whereas a recent population-based analysis suggested otherwise, although the latter relied on imputation. To reconcile the findings of that study by critically evaluating the handling of missing data.

PATIENTS AND METHODS

• Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10 596).

• Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND.

• To examine differences in approaches with respect to handling missing data, separate analyses were performed: (i) imputed population; (ii) exclusion of patients with missing data; and (iii) inclusion of patients with missing data as a sub-category.

RESULTS

• Overall, 2916 (28%) patients had missing tumour grade.

• In multivariable analyses, our findings showed that increasing the extent of LND was associated with a significant protective effect on CSM in patients with pN1 after imputation (hazard ratio [HR], 0.82; P = 0.04).

• By contrast, the extent of LND was no longer significantly associated with a lower risk of CSM after excluding patients with a missing tumour grade (HR, 0.83; P = 0.1) or when including patients with missing tumour grade as a sub-category (HR, 0.82; P = 0.05).

CONCLUSIONS

• The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy.

• The different methodologies employed to account for missing data may introduce important biases.

• Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.

Read Previous Articles of the Week

Editorial: Does performing LND at nephrectomy give a survival benefit or not?

January 15, 2014/by Jared Whitson

We read with interest the article by Sun et al. [1] in this issue of the BJU International. We were pleased to see another research group interested in this important aspect of the management of patients with lymph-node-positive non-metastatic RCC. The question of the benefits of lymphadenectomy in such patients could not be answered by the European Organization for Research and Treatment of Cancer randomized trial [2], as only 4% of clinically node-negative patients had micrometastatic disease.

Given some of the complexities involved in the analysis of Surveillance, Epidemiology and End Results data and the particular statistical analysis we used in showing a benefit to increasing nodal yield in patients with positive nodes [3], we were reassured that Sun et al. were able to validate our findings when replicating our data extraction and analysis. They performed two additional analyses and the four results are shown in Table 1.

While Sun et al. concluded that multiple imputation introduces bias into the findings, inspection of the estimates of the impact of lymph node dissection (the hazard ratio) appear identical. If bias is a deviation of an estimate from the truth [4], we would argue that Sun et al. found no evidence of bias introduced by the multiple imputation method. This is not to say that all four analyses are free from potential bias – the reported hazard ratios may in fact still be biased results – but that there is no more bias in the multiple imputation model than in the others. In addition, we were somewhat surprised to see the use of a missing indicator approach proposed as less likely than multiple imputation to introduce bias as studies have shown the opposite [5].

Furthermore, the CIs show that the benefit to extent of lymphadenectomy may be as great as a 34% reduction in cancer-related death, with exclusion of all but a 5% increase in death associated with the procedure. CIs provide extremely valuable information, particularly in the setting of marginally significant or nonsignificant P values. Sun et al. could have strengthened their paper on statistical considerations by discussing this further. In fact, we would argue that their additional analyses lend further support to the potential benefit of the extent of lymphadenectomy.

The most notable difference across the analyses is a drift in the P value. We would argue that this mirrors the loss in power associated with the censoring of almost 3000 patients (28%) with missing grades. In addition, grade does not appear to be missing at random, as patients with missing tumour grades were associated with larger tumours, higher local stage, increased probability of nodal involvement and increased risk of kidney cancer death. The censoring of such patients may in and of itself introduce bias, although again the hazard ratios do not seem to reflect this. The devaluation of the P value continues to be an active area of biostatistical research, although in general journals have not foregone its inclusion in favour of an entirely Bayesian approach [6]. We believe that, in this case, Sun et al. have taken a far too traditional approach to interpretation of small differences in P values, particularly in the setting of changing sample sizes.

We agree with Sun et al. that consideration of another randomized trial focused on patients at high risk of nodal involvement or with clinically apparent nodes on CT is warranted based upon our combined results.

Jared M. Whitson and Maxwell Meng
Department of Urology, Kaiser Permanente South Sacramento Medical Center, Sacramento, CA, USA

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References

Sun M, Trinh Q-D, Bianchi M et al. Extent of lymphadenectomy does not improve survival of patients with renal cell carcinoma and nodal metastases: biases associated with handling of missing data. BJU Int 2014; 113: 36–42
Blom JH, van Poppel H, Marechal JM et al. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009; 55: 28–34
Whitson JM, Harris CR, Reese AC, Meng MV. Lymphadenectomy improves survival of patients with renal cell carcinoma and nodal metastases. J Urol 2011; 185: 1615–1620
Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet 2002; 359: 248–252
Greenland S, Finkle WD. A critical look at methods for handling missing covariates in epidemiologic regression analyses. Am J Epidemiol 1995; 142: 1255–1264
Goodman SN. Toward evidence-based medical statistics. 2: the Bayes factor. Ann Intern Med 1999; 130: 1005–1013

Video: Survival for RCC and nodal metastases

January 15, 2014/by admin Z.9

Extent of lymphadenectomy does not improve the survival of patients with renal cell carcinoma and nodal metastases: biases associated with the handling of missing data

Maxine Sun and Quoc-Dien Trinh contributed equally to this study.

Read the full article

OBJECTIVE

PATIENTS AND METHODS

• Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10 596).

• Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND.

RESULTS

• Overall, 2916 (28%) patients had missing tumour grade.

CONCLUSIONS

• The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy.

• The different methodologies employed to account for missing data may introduce important biases.

• Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.

Article of the week: What predicts cancer-specific survival after renal cancer recurrence?

November 27, 2013/by admin Z.9

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

Time to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma – results from a comprehensive multi-centre database (CORONA/SATURN-Project)

Sabine D. Brookman-May¹, Matthias May², Shahrokh F. Shariat³, Giacomo Novara⁴, Richard Zigeuner⁵, Luca Cindolo⁶, Ottavio De Cobelli⁷, Cosimo De Nunzio⁸, Sascha Pahernik⁹, Manfred P. Wirth¹⁰, Nicola Longo¹¹, Alchiede Simonato¹², Sergio Serni¹³, Salvatore Siracusano¹⁴, Alessandro Volpe¹⁵, Giuseppe Morgia¹⁶, Roberto Bertini¹⁷, Orietta Dalpiaz⁵, Christian Stief¹, and Vincenzo Ficarra^4,18; Members of the CORONA-Project, the SATURN-Project, and the Young Academic Urologists Renal Cancer Group

¹Department of Urology, Ludwig-Maximilians-University Munich, Campus Grosshadern, Munich, ²Department of Urology, St. Elisabeth Hospital Straubing, Straubing, Germany, ³Department of Urology and Division of Medical Oncology, Weill Cornell Medical College, New York, NY, USA, ⁴Department of Urology, University of Padua, Padua, Italy, ⁵Department of Urology, Medical University of Graz, Graz, Austria, ⁶Department of Urology, S. Pio Da Pietrelcina Hospital, Vasto, ⁷Department of Urology, European Institute of Oncology, Milan, ⁸Department of Urology, S. Andrea Hospital, Rome, Italy, ⁹Department of Urology, University of Heidelberg, Heidelberg, ¹⁰Department of Urology, Carl Gustav Carus Hospital, University of Dresden, Dresden, Germany, ¹¹Department of Urology, University of Naples Federico II, Napoli, ¹²‘Luciano Giuliani’ Department of Urology, University of Genoa, Genoa, ¹³Department of Urology, University of Florence, Careggi Hospital, Florence, ¹⁴Department of Urology, University of Trieste, Trieste, ¹⁵Department of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, ¹⁶Departments of Urology, University of Catania, Catania, ¹⁷Department of Urology, Vita-Salute University San Raffaele, Milan, ¹⁸Department of Urology, Vita-Salute University San Raffaele, Milan, Italy, and OLV Robotic Surgery Institute, Aalst, Belgium

S.D.B.-M. and M.M contributed equally to this manuscript

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OBJECTIVES

• To assess the prognostic impact of time to recurrence (TTR) on cancer-specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron-sparing surgery.

• To analyse differences in clinical and histopathological criteria between patients with early and late recurrence.

PATIENTS AND METHODS

• Of 13 107 patients with RCC from an international multicentre database, 1712 patients developed recurrence in the follow-up (FU), at a median (interquartile range) of 50.1 (25–106) months.

• In all, 1402 patients had recurrence at ≤5 years (Group A) and 310 patients beyond this time (Group B).

• Differences in clinical and histopathological variables between patients with early and late recurrence were analysed.

• The influence of TTR and further variables on CSS after recurrence was assessed by Cox regression analysis.

RESULTS

• Male gender, advanced age, tumour diameter and stage, Fuhrman grade 3–4, lymphovascular invasion (LVI), and pN + stage were significantly more frequent in patients with early recurrence, who had a significantly reduced 3-year CSS of 30% compared with patients in Group B (41%; P = 0.001).

• Age, gender, tumour histology, pT stage, and continuous TTR (hazard ratio 0.99, P = 0.006; monthly interval) independently predicted CSS.

• By inclusion of dichotomised TTR in the multivariable model, a significant influence of this variable on CSS was present until 48 months after surgery, but not beyond this time.

CONCLUSIONS

• Advanced age, male gender, larger tumour diameters, LVI, Fuhrman grade 3–4, pN + stage, and advanced tumour stages are associated with early recurrence.

• Up to 4 years from surgery, a shorter TTR independently predicts a reduced CSS after recurrence.

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Editorial: Better late than early for long-term survival in patients with recurrence after renal carcinoma

November 27, 2013/1 Comment/by Kathie Wong

In this paper, Brookman-May et al. [1] used a large multi-institutional database of over 13 000 patients from 23 centres in both Europe and the USA to examine the prognostic indicators of cancer-specific survival (CSS) in patients who had recurrence after primary surgery for RCC. Their analysis was based on a subset of 1712 patients who had recurrence during a median follow-up period of 50 months. All patients had undergone either radical nephrectomy or nephron-sparing surgery, with no evidence of metastasis at the time of surgery.

The authors have previously shown, in a related study based on a subset of 5000 patients from the same database, that lymphovascular invasion, Fuhrman grade 3–4, and pT stage > pT1 at the time of diagnosis were significantly associated with the development of late recurrence (defined as after >5 years) [2]. In this paper, the primary objective was to look at the effect of time to tumour recurrence (TTR) on CSS. In addition, clinical and histopathological comparisons were made between patients with early (<5 years) and late recurrence (>5 years).

Patients often want to know whether if they are recurrence-free after a period of time, their subsequent risk of dying from recurrence is reduced; this paper goes some way towards answering this question and showing that those with later recurrence had improved survival times. Specifically, the authors found that TTR was an independent predictor of CSS; i.e. if patients recurred early they had a worse CSS than those recurring late. This is similar to results from another group who reported that recurrent disease, particularly before 12 months, was associated with a poorer prognosis [3]. In the first 4 years of follow-up, a shorter TTR independently predicted lower CSS after recurrence [1]. When divided into those with early recurrence, Group A (N = 1402), and those with late recurrence, Group B (N = 310), patients in Group A were more likely to be male, of advanced age, have a greater tumour diameter and stage, have Fuhrman grade 3–4, with lymphovascular invasion and positive lymph node disease, than those in Group B. Patients in Group A had a 3-year CSS of 30% compared with those in Group B whose CSS was better at 41%. Age and gender were also independent predictors of CSS.

These results can help to guide the aftercare management of patients after primary surgery. Currently, primary surgery is the only recommended option for patients with localized RCC, although results from several phase III clinical trials looking at the role of adjuvant therapy, such as the SORCE, PROTECT and S-TRAC trials, are still awaited [4]. Furthermore, it is not known which group of patients are suitable for adjuvant chemotherapy, which is reflected in the subtly differing eligibility criteria for recruitment to the various trials [4]. The authors of the present study pointed out that a method of risk stratification may be useful to allow equal representation of early and late recurrence patients in treatment arms for clinical trials. Potentially, understanding the predictors of early recurrence may help to identify patients for whom adjuvant therapy may be beneficial.

Only 12% of patients with localized RCC in the present cohort developed recurrence after surgery [1]. This rate is lower than that found in the literature, where 20–30% recurrence rates of localized RCC have been reported [2, 5, 6]. Brookman-May et al. speculate that this lower rate is attributable to both an increase in early detection as well as improved surgical management in recent years. Furthermore, they acknowledge that the database is heterogeneous and that the study therefore has all the inherent limitations of a retrospective study.

The present paper clearly shows that the earlier the recurrence after surgery the lower the survival rate, but a clear strategy for the surveillance of localized RCC after primary surgery is currently lacking. Most follow-up protocols exercise a blanket ‘one for all’ policy with follow-up spaced at regular intervals to ensure patients who recur are detected early. Such a policy may not be intensive enough to detect early recurrence in some patients and may be excessive for the majority of patients where the risk of recurrence is low. Risk stratification of patients, by understanding the predictors of CSS after surgery, may help to tailor surveillance protocols to the individual and identify those for whom adjuvant therapy may be beneficial.

Kathie Wong and Ben Challacombe
The Urology Centre, Guy’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

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References

Brookman-May S, May M, Shariat S et al. Time to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma – results from a comprehensive multi centre database (CORONA/SATURN Project). BJU Int 2013; 112: 909–916
Brookman-May S, May M, Shariat SF et al. Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project). Eur Urol 2012; 64: 472–477
Rodriguez-Covarrubias F, Gomez-Alvarado MO, Sotomayor M et al. Time to recurrence after nephrectomy as a predictor of cancer-specific survival in localized clear-cell renal cell carcinoma. Urol Int 2011; 86: 47–52
Kim SP, Crispen PL, Thompson RH et al. Assessment of the pathologic inclusion criteria from contemporary adjuvant clinical trials for predicting disease progression after nephrectomy for renal cell carcinoma. Cancer 2012; 118: 4412–4420
Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Five-year survival after surgical treatment for kidney cancer: a population-based competing risk analysis. Cancer 2007; 109: 1763–1768
Breda A, Konijeti R, Lam JS. Patterns of recurrence and surveillance strategies for renal cell carcinoma following surgical resection. Expert Rev Anticancer Ther 2007; 7: 847–862

Article of the week: Karakiewicz was right: nomograms are very robust

September 25, 2013/by admin Z.9

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.

Assessing the accuracy and generalizability of the preoperative and postoperative Karakiewicz nomograms for renal cell carcinoma: results from a multicentre European and US study

Luca Cindolo¹, Paolo Chiodini², Sabine Brookman-May⁸, Ottavio De Cobelli³, Matthias May⁸, Stefano Squillacciotti⁴, Cosimo De Nunzio⁵, Andrea Tubaro⁵, Ioan Coman⁷, Bodgan Feciche⁷, Michael Truss⁹, Manfred P. Wirth¹⁰, Orietta Dalpiaz¹¹, Thomas F. Chromecki¹¹, Shahrock F. Shariat^12,13,14, Manuel Sanchez-Chapado¹⁵, Maria del Carmen Santiago Martin¹⁵, Bernardo Rocco¹⁶, Luigi Salzano⁶, Giuseppe Lotrecchiano⁶, Francesco Berardinelli¹, and Luigi Schips¹

¹“S. Pio Da Pietrelcina” Hospital, Dept. of Urology, Vasto, Italy, ²Second University of Naples, Dept. of Public Health, Naples, Italy, ³European Institute of Oncology, Dept. of Urology, Milan, Italy, ⁴“San Carlo” Hospital, Dept. of Urology, Rome, Italy, ⁵“S. Andrea” Hospital, Dept. of Urology, Rome, Italy, ⁶“G. Rummo” Hospital, Dept. of Urology, Benevento, Italy, ⁷Clinical Municipal Hospital, Dept. of Urology, Cluj-Napoca, Romania, ⁸“Ludwig-Maximilians” University Munich, Dept. of Urology, Campus Grosshadern, Munich, Germany, ⁹Klinikum Dortmund, Dept. of Urology, Dortmund, Germany, ¹⁰Uniklinikum “Carl Gustav Carus”; Dept. of Urology, Dresden, Germany, ¹¹Medical University of Graz, Graz, Austria, ¹²Weill Cornell Medical Center, New York-Presbyterian Hospital, Dept. of Urology, New York, NY, USA, ¹³Weill Cornell Medical Center, New York-Presbyterian Hospital, Division of Medical Oncology, New York, NY, USA, ¹⁴University of Texas Southwestern, Dept. of Urology, Dallas, TX, USA, ¹⁵Department of Urology, Hospital Universitario Principe de Asturias, Alcala de Henares, Spain, and ¹⁶Fondazione Ca’ granda, Ospedale Maggiore Policlinico, Dept. of Urology, University of Milan, Milan, Italy

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OBJECTIVE

• To assess the accuracy and generalizability of the pre- and postoperative Karakiewicz nomograms for predicting cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC).

PATIENTS AND METHODS

• This retrospective study included 3231 patients from European and US centres, who were treated by radical or partial nephrectomy for RCC between 1992 and 2010.

• Prognostic scores for each patient were calculated and the primary endpoint was CSS.

• Discriminating ability was assessed by Harrell’s c-index for censored data. The ‘validation by calibration’ method proposed by Van Houwelingen was used for checking the calibration of covariate effects. Calibration was graphically explored.

RESULTS

• Local and systemic symptoms were present in 23.2% and 9.1% of the patients, respectively.

• The median follow-up (FU) was 49 months. At the last FU, 408 cancer-related deaths were recorded, Kaplan–Meier estimates of CSS (with 95% confidence intervals [CIs]) at 5 and 10 years were 0.86 (0.84–0.87) and 0.77 (0.75–0.80), respectively.

• Both nomograms discriminated well. Stratified c-indices for CSS were 0.784 (95% CI 0.753–0.814) for the preoperative nomogram, and 0.842 (95% CI 0.816–0.867) for the postoperative one, with a significant difference between the two values (P < 0.001).

• The covariate-based predictions on our data for both nomograms were valid. The calibration plots showed no relevant departures from ideal predictions.

CONCLUSIONS

• The results suggest that the postoperative Karakiewicz nomogram discriminates substantially better than the preoperative one.

• These nomogram-based predictions may be used as benchmark data for pretreatment and postoperative decision-making in patients at various stages of RCC.