Tag Archive for: prognosis

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Article of the week: Men under 50 should not be discouraged from radical prostatectomy

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.

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. Andreas Becker discussing his paper.

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

Functional and oncological outcomes of patients aged <50 years treated with radical prostatectomy for localised prostate cancer in a European population

Andreas Becker*, Pierre Tennstedt*, Jens Hansen*, Quoc-Dien Trinh, Luis Kluth, Nabil Atassi*, Thorsten Schlomm*, Georg Salomon*, Alexander Haese*, Lars Budaeus*, Uwe Michl*, Hans Heinzer*, Hartwig Huland*, Markus Graefen* and Thomas Steuber*

*Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada, andDepartment of Urology, University-Hospital Hamburg-Eppendorf, Hamburg, Germany

OBJECTIVE

• To address the biochemical and functional outcomes after radical prostatectomy (RP) of men aged <50 years in a large European population.

PATIENTS AND METHODS

• Among 13 268 patients who underwent RP for clinically localised prostate cancer at our centre (1992–2011), 443 (3.3%) men aged <50 were identified.

• Biochemical recurrence (BCR) and functional outcomes (International Index of Erectile Function [IIEF-5], use of pads), were prospectively evaluated and compared between men aged <50 years and older patients.

RESULTS

• Men aged <50 years were more likely to harbour D’Amico low-risk (49.4 vs 34.9%, P < 0.001), organ-confined (82.6 vs 69.4%, P < 0.001) and low-grade tumours (Gleason score <7: 33.1 vs 28.7%, P < 0.001).

• Multivariate Cox regression analysis showed that age <50 years (hazard ratio 0.99; confidence interval 0.72–1.31; P = 0.9) was not a predictor of BCR.

• Urinary continence was more favourable in younger patients, resulting in continence rates of 97.4% vs 91.6% in most recent years (2009–2011) for patients aged <50 vs ≥50 years.

• After RP, a median IIEF-5 drop of 4 points in younger men vs 8 points in older patients was recorded (P < 0.001).

• Favourable recovery of urinary continence and erectile function in patients aged <50 years compared with their older counterparts was confirmed after multivariable adjustment.

CONCLUSION

• Men aged <50 years diagnosed with localised prostate cancer should not be discouraged from RP, as the postoperative rates of urinary incontinence and erectile dysfunction are low and probability of BCR-free survival at 2 and 5 years is high.

 

Editorial: Radical prostatectomy at young age

Becker et al. [1] investigated a large sample of young patients (aged <50 years) who underwent radical prostatectomy during a 20-year period in a high-volume European centre. In this study [1], men aged <50 years had a significantly more favourable functional outcome (continence rates [0–1 pads] 97% vs 92%; International Index of Erectile Function [IIEF] score drop of 4 vs 8 points), compared with their older counterparts. Biochemical tumour control was higher in younger patients in univariate (5-year rates 81% vs 70%) but not in multivariate analysis.

In studies in the pre-PSA era, young age at prostate cancer diagnosis was often associated with adverse tumour-related outcome [2]. Possibly, the disadvantage of younger patients was attributable to rapidly growing high-grade tumours causing symptoms at a young age in the absence of a dilution by favourable early detected low-grade cancers. In contemporary patients, the opposite is observed [1]. As the impact of age vanished after controlling for tumour-related prognostic factors reflecting the presence of more favourable disease criteria in younger men, it may be considered likely that PSA-based early detection enriched favourable parameters in the younger subgroup. Altogether, prostate cancer biology is probably not meaningfully associated with age. Outcome differences, even in randomised trials [3, 4], are rather caused by age-related differences in the approach to prostate cancer diagnostics and early detection than in actual biological differences.

The relative favourable functional outcome in younger patients [1] supports early curative treatment in this population. Currently available active surveillance studies have very limited follow-up and were performed mainly in elderly patients with significant comorbidity [5]. Currently, in Germany the further life expectancy in men aged 50 years is ≈30 years [6]. In a contemporary active surveillance study, narrowly half of patients received active treatment within 10 years [5]. Therefore, most men starting active surveillance at an age of 50 years will subsequently receive active treatment. This treatment will then be performed at a greater age where the chances for satisfactory functional recovery are less favourable.

The inferior tumour control rates in patients receiving robot-assisted surgery is another remarkable finding of this study (hazard ratio 1.4, 95% CI 0.99–1.9, P = 0.06 in the multivariate analysis). Although the significance level was narrowly failed, this observation cannot be ignored. It was accompanied by an increased continence recovery rate after robot-assisted surgery suggesting that it may probably not be attributed to the learning curve. Less radical removal of the prostate with more sparing of neurovascular structures and bladder neck might be a conceivable explanation of this phenomenon. In this study [1], the prognostic impact of robot-assisted approach was in a similar range as a positive surgical margin (hazard ratio 1.5, 95% CI 1.4–1.7).

Current clinical guidelines discourage prostate cancer screening in average-risk men aged <50 years [7]. It remains to be seen in which degree these recommendations will affect clinical practice and outcome parameters in this age group in the years ahead.

Manfred P. Wirth and Michael Froehner
Department of Urology, University Hospital ‘Carl Gustav Carus’, Dresden University of Technology, Dresden, Germany

References

  1. Becker A, Tennstedt P, Hansen J et al. Functional and oncological outcomes of patients younger than 50 years treated with radical prostatectomy for localized prostate cancer in a European population. BJU Int 2014; 114: 38–45
  2. Parker CC, Gospodarowicz M, Warde P. Does age influence the behaviour of localized prostate cancer? BJU Int 2001; 87: 629–637
  3. 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
  4. Froehner M, Wirth MP. Early prostate cancer – treat or watch? N Engl J Med 2011; 365: 568
  5. Selvadurai ED, Singhera M, Thomas K et al. Medium-term outcomes of active surveillance for localised prostate cancer. Eur Urol 2013; 64: 981–987
  6. Statistisches Bundesamt. Periodensterbetafeln für Deutschland 1871/1881 bis 2008/2010 [Period death tables for Germany 1871/1881 bis 2008/2010]. Wiesbaden 2012. Available at: https://www.destatis.de/DE/Publikationen/Thematisch/Bevoelkerung/Bevoelkerungsbewegung/PeriodensterbetafelnPDF_5126202.pdf?__blob=publicationFile [Website in German]. Accessed 12 July 2013.
  7. Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2013; 158: 761–769

Video: RP for younger men – low risk and high survival rate

Functional and oncological outcomes of patients aged <50 years treated with radical prostatectomy for localised prostate cancer in a European population

Andreas Becker*, Pierre Tennstedt*, Jens Hansen*, Quoc-Dien Trinh, Luis Kluth, Nabil Atassi*, Thorsten Schlomm*, Georg Salomon*, Alexander Haese*, Lars Budaeus*, Uwe Michl*, Hans Heinzer*, Hartwig Huland*, Markus Graefen* and Thomas Steuber*

*Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada, andDepartment of Urology, University-Hospital Hamburg-Eppendorf, Hamburg, Germany

OBJECTIVE

• To address the biochemical and functional outcomes after radical prostatectomy (RP) of men aged <50 years in a large European population.

PATIENTS AND METHODS

• Among 13 268 patients who underwent RP for clinically localised prostate cancer at our centre (1992–2011), 443 (3.3%) men aged <50 were identified.

• Biochemical recurrence (BCR) and functional outcomes (International Index of Erectile Function [IIEF-5], use of pads), were prospectively evaluated and compared between men aged <50 years and older patients.

RESULTS

• Men aged <50 years were more likely to harbour D’Amico low-risk (49.4 vs 34.9%, P < 0.001), organ-confined (82.6 vs 69.4%, P < 0.001) and low-grade tumours (Gleason score <7: 33.1 vs 28.7%, P < 0.001).

• Multivariate Cox regression analysis showed that age <50 years (hazard ratio 0.99; confidence interval 0.72–1.31; P = 0.9) was not a predictor of BCR.

• Urinary continence was more favourable in younger patients, resulting in continence rates of 97.4% vs 91.6% in most recent years (2009–2011) for patients aged <50 vs ≥50 years.

• After RP, a median IIEF-5 drop of 4 points in younger men vs 8 points in older patients was recorded (P < 0.001).

• Favourable recovery of urinary continence and erectile function in patients aged <50 years compared with their older counterparts was confirmed after multivariable adjustment.

CONCLUSION

• Men aged <50 years diagnosed with localised prostate cancer should not be discouraged from RP, as the postoperative rates of urinary incontinence and erectile dysfunction are low and probability of BCR-free survival at 2 and 5 years is high.

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

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

Read the full article
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.

 

 

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

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

Read the full article

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 bladderBJU Int 2014; 113: 393–398
  2. Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplantsTransplant Proc 1973; 5: 253–259
  3. Gantt CL. Red blood cells for cancer patientsLancet 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 carcinomaCan 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 cystectomyEur Urol 2013; 63: 839–845

Video: Peri-operative blood transfusion: outcomes in patients with bladder cancer

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

Read the full article
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.

 

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
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.

 

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
References
  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.

Article of the Week: Better fit than fat when it comes to radical cystectomy for bladder cancer

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.

Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy

Thomas F. Chromecki1,2*, Eugene K. Cha1*, Harun Fajkovic1,3, Michael Rink1,4, Behfar Ehdaie1, Robert S. Svatek5, Pierre I. Karakiewicz6, Yair Lotan7, Derya Tilki8, Patrick J. Bastian8, Siamak Daneshmand9,Wassim Kassouf10, Matthieu Durand1, Giacomo Novara11, Hans-Martin Fritsche12, Maximilian Burger12, Jonathan I. Izawa13, Antonin Brisuda14, Marek Babjuk14, Karl Pummer2 and Shahrokh F. Shariat1

1Weill Medical College of Cornell University, New York, NY, USA, 2Medical University Graz, Graz, Austria, 3Landeskrankenhaus St Poelten, St Poelten, Austria, 4University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, 5University of Texas Health Science Center San Antonio, San Antonio, TX, USA, 6University of Montréal, Montréal, QC, Canada, 7University of Texas Southwestern Medical Center, Dallas, TX, USA, 8Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Munich, Germany, 9University of Southern California Keck School of Medicine and Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 10McGill University Health Centre, Montréal, QC, Canada, 11University of Padua, Padua, Italy, 12Caritas St Josef Medical Centre, University of Regensburg, Regensburg, Germany, 13University of Western Ontario, London, ON, Canada, and 14Hospital Motol, 2nd Faculty of Medicine, Charles University, Praha, Czech Republic
*These authors contributed equally.

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OBJECTIVE

• To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series.

PATIENTS AND METHODS

• Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded.

• Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality.

• BMI was analysed as a continuous and categorical variable (<25 vs 25–29 vs 30 kg/m2).

RESULTS

• Median BMI was 28.8 kg/m2 (interquartile range 7.9); 25.3% had a BMI <25 kg/m2, 32.5% had a BMI between 25 and 29.9 kg/m2, and 42.2% had a BMI 30 kg/m2.

• Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI.

• In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46–1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24–1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60–2.05, P < 0.001). The main limitation is the retrospective design of the study.

CONCLUSIONS

• Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB.

• Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.

 

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Editorial: Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy

Michael R. Abern, Stephen J. Freedland and Brant A. Inman

Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USA

Obesity is a worldwide epidemic: it is estimated over 300 million adults are obese and over 1 billion are overweight. As obesity is a risk factor for cancers and is modifiable, the authors of this report retrospectively analyse the association between body mass index (BMI) and outcomes in a large multinational cohort of bladder cancer patients that underwent radical cystectomy. They found that obese patients were older and more likely to have high-grade tumours. Furthermore, obese patients received inferior lymphadenectomies, had more positive margins, and were less likely to receive adjuvant chemotherapy. The end result is an association between obesity and bladder cancer recurrence, and both cancer-specific and overall mortality.

Although these data suggest that obesity is associated with poor radical cystectomy outcomes, this contrasts with evidence showing no link between obesity and bladder cancer mortality in population-based trials such as the Cancer Prevention Study II, which prospectively followed over 900 000 participants. Why the discrepancy? One possible explanation is the presence of confounding factors and one possible confounder is the presence of type 2 diabetes. In population-based studies that considered both BMI and diabetes, people with diabetes were noted to have an increased risk of developing bladder cancer independent of BMI, whereas the converse was not true. Additionally, diabetes has been associated with recurrence and progression of non-muscle invasive bladder cancer whereas obesity has not. The impact of diabetes was not adequately addressed in the current study.

Other limitations also probably affect the results. In the current study, overweight patients (BMI 25–30) had significantly better cancer-specific survival (hazard ratio 0.80, P = 0.01) than those of ‘normal’ weight (BMI < 25). However, a threshold BMI ≥ 30 has been shown to have poor sensitivity for obesity in elderly populations, with over 25% of patients with BMI under 30 qualifying as obese based on body fat. This may result in an overstatement of the effect of obesity. Conversely, the inclusion of underweight patients (BMI < 18.5) in the ‘normal’ group may underestimate the effect between obesity and outcome, as cachexia may be associated with poor outcomes. Another factor mentioned by the authors is the inferior lymphadenectomies performed in obese patients, which introduces a detection bias for lymph node positivity, the strongest predictor after advanced stage for all of their tested outcomes on multivariate analysis (hazard ratio 2.01–2.33, P < 0.001).

Although the true effect of obesity may be hard to quantify with these data, all would agree that maintaining a non-obese bodyweight will help many disease states with little apparent harm. Patients undergoing neoadjuvant chemotherapy before radical cystectomy have a 3-month window to lose weight and exercise more. This could improve surgical outcomes, and possibly tolerance of chemotherapy. Furthermore, if we can prove that obesity leads to increased bladder cancer recurrence or progression, a window of opportunity may exist when a low-risk tumour is diagnosed. Otherwise, we are left with the eighteenth century wisdom of Benjamin Franklin: ‘An ounce of prevention is worth a pound of cure.’

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