Tag Archive for: cancer-specific survival


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

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.

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 Ficarra4,18; 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


• 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.


• 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.


• 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.


• 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.


Read Previous Articles of the Week



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

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


  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

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.

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. Shariat12,13,14, 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

Read the full article

• 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).


• 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.


• 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.


• 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.


Read Previous Articles of the Week


Editorial: External validation of Karakiewicz models: do they hold up?

Cancer-specific survival (CSS) in patients with RCC depends on important prognostic factors including specific clinical signs or symptoms, tumour-related factors and various laboratory findings. To better predict prognosis and aid patient counselling, several investigators have developed tools which have greatly enhanced our ability to predict outcomes in patients with RCC. For instance, Kattan et al. [1] have combined manner of presentation, tumour histology, tumour size and pathological stage to develop a nomogram that predicts cancer-free survival after nephrectomy. The stage, size, grade, and necrosis (SSIGN) score is another predominant model that provides individualized information for patients with clear-cell RCC. It incorporates the 1997 TNM stage, tumour size, nuclear grade and presence of tumour necrosis to predict recurrence and survival after radical nephrectomy [2]. The Karakiewicz nomogram [3] was developed to predict CSS based on multi-institutional data. The preoperative nomogram includes patient age, gender, clinical stage, presence of metastases, tumour size and symptom classification. The postoperative one includes TNM stage, tumour size, Fuhrman grade, histological subtype and local symptoms. Tan et al. [4] compared several prognostic systems (the Karakiewicz, Kattan and Sorbellini nomograms, and the Leibovich model) and concluded that in terms of individual counselling, the postoperative Karakiewicz nomogram is likely to be more useful than other models and provides excellently calibrated CSS estimates; however, before a prediction tool becomes popular in clinical use, it is crucial to perform internal and external validation to prove its generalizability. For example, the UCLA integrated staging system (UISS) helps to identify patients with localized or metastatic disease at low, intermediate, and high risk of disease progression and has been validated internally and externally [5].

The present study by Cindolo et al. [6] aims to assess the accuracy and generalizability of the pre- and postoperative Karakiewicz nomograms in predicting CSS. It is a retrospective study involving >3000 patients from multiple European and US centres between 1992 and 2010. They include high-, mid- and low-volume institutes, as well as different populations. This helps to provide a heterogenous study cohort to better reflect the real clinical situation and hence to improve the reproducibility of the nomogram. The preoperative and postoperative models have a good predictive ability with a stratified C-index of 0.784 and 0.842, respectively, and the latter discriminates substantially better. The authors conclude that the Karakiewicz nomograms proved to have excellent accuracy and generalizability.

With more RCC therapeutic options including surveillance, ablation, surgery and systemic therapies, better prediction tools are needed to help clinical decision-making. A wealth of literature now supports the hypothesis that nomograms and artificial neural networks are superior to classic TNM staging systems in risk assessment; therefore, these predictive tools are important to guide the counselling, treatment and follow-up of patients with RCC.

Peggy Chu1 and Ringo Wing-Hong Chu2
1Department of Surgery, Tuen Mun Hospital, and 2Department of Surgery, Kwong Wah Hospital, Hong Kong, China

Read the full article
  1. Kattan MW, Reuter V, Motzer RJ et al. A postoperative prognostic nomogram for renal cell carcinoma. J Urol 2001; 166: 63–7
  2. Frank I, Blute ML, Cheville JC et al. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the sign score. J Urol 2002; 168: 2395–400
  3. Karakiewicz PI, Briganti A, Chun FK et al. Multi-institutional validation of a new renal cancer-specific survival nomogram. J Clin Oncol 2007; 25: 1316–22
  4. Tan MH, Li H, Choong CV et al. The Karakiewicz nomogram is the most useful clinical predictor for survival outcomes in patients with localized renal cell carcinoma. Cancer 2011; 117: 5314–24
  5. Cindolo L, Chiodini P, Gall C et al. Validation by calibration of the UCLA integrated staging system prognostic model for nonmetastatic renal cell carcinoma after nephrectomy. Cancer 2008; 113: 65–71
  6. Cindolo L, Chiodini P, Brookman-May S et al. Assessing the accuracy and generalizability of the preoperative and postoperative Karakiewicz nomograms for renal cell carcinoma: results from a multicentre European and US study. BJU Int 2013; 112: 578–584.
© 2024 BJU International. All Rights Reserved.