Category: Article of the Week

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

March 26, 2014/by Shamim Khan

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

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

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

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

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

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

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

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

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

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References

Kluth LA, Xylinas E, Rieken M et al. Impact of perioperative blood transfusion on the outcome of patients undergoing radical cystectomy for urothelial carcinoma of the bladder. BJU Int 2014; 113: 393–398
Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973; 5: 253–259
Gantt CL. Red blood cells for cancer patients. Lancet 1981; 2: 363
Sadeghi N, Badalato GM, Hruby G, Kates M, McKiernan JM. The impact of perioperative blood transfusion on survival following radical cystectomy for urothelial carcinoma. Can J Urol 2012; 19: 6443–6449
Linder BJ, Frank I, Cheville JC et al. The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013; 63: 839–845

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

March 26, 2014/by admin Z.9

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

Luis A. Kluth^1,3, Evanguelos Xylinas^1,4, Malte Rieken^1,5, 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. Shariat^1,2,11

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

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

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OBJECTIVE

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

PATIENTS AND METHODS

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

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

RESULTS

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

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

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

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

CONCLUSIONS

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

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

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.

Read the full article

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.

Read the full article

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: Restored renal function after RN

March 12, 2014/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.

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

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

Trends in renal function after radical nephrectomy: a multicentre analysis

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

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

Read the full article

OBJECTIVE

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

PATIENTS AND METHODS

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

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

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

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

RESULTS

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

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

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

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

CONCLUSIONS

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

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

Read Previous Articles of the Week

Editorial: Renal functional recovery after radical nephrectomy

March 12, 2014/by Ithaar Derweesh

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

Read the full article

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

References

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

Video: Trends in renal function after RN

March 12, 2014/by admin Z.9

Trends in renal function after radical nephrectomy: a multicentre analysis

Read the full article

OBJECTIVE

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

PATIENTS AND METHODS

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

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

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

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

RESULTS

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

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

CONCLUSIONS

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

Article of the month: Targeting the androgen receptor

March 5, 2014/by admin Z.9

In addition to the article itself, there is an accompanying video of a lecture from Professor David Neal, filmed at the Society of Academic Research and Surgery: 2013 Annual Meeting.

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

The transcriptional programme of the androgen receptor (AR) in prostate cancer

Alastair D. Lamb, Charlie E. Massie and David E. Neal

Cambridge University Department of Urology, Addenbrooke’s Hospital and Cancer Research UK (CRUK) Cambridge Institute, Cambridge, UK

Read the full article

ABSTRACT

• The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth.

• AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone.

• Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC.

• The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease.

• Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors.

LINK TO VIDEO

Lecture filmed at the Society of Academic Research and Surgery: 2013 Annual Meeting. Video available from The Royal Society of Medicine https://www.rsmvideos.com/videoPlayer/?vid=340

Read Previous Articles of the Week

Article of the week – Prostate cancer: Sun shines light on surgical survival

February 26, 2014/1 Comment/by admin Z.9

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

Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation

Maxine Sun*, Jesse D. Sammon^†, Andreas Becker*, Florian Roghmann*, Zhe Tian*, Simon P. Kim^‡, Alexandre Larouche*, Firas Abdollah*, Jim C. Hu^§, Pierre I. Karakiewicz*^¶ and Quoc-Dien Trinh**

*Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada, ^†VUI Center for Outcomes Research, Analytics and Evaluation, Henry Ford Health Systems, Detroit, MI, ^‡Department of Urology, Yale University, New Haven, CT, ^§Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, ^¶Department of Urology, University of Montreal Health Center, Montreal, Canada and **Department of Surgery, Division of Urology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

MS and J.D.S contributed equally to the work.

Read the full article

OBJECTIVE

• To compare efficacy between radical prostatectomy (RP), radiotherapy and observation with respect to overall survival (OS) in patients with clinically localized prostate cancer (PCa).

METHODS

• Using data (1988–2005) from the Surveillance, Epidemiology, and End Results–Medicare linked database, 67 087 men with localized PCa were identified.

• The prevalence of the initial treatment strategy was quantified according to patients’ life expectancy ([LE] <10 vs ≥10 years) at initial diagnosis and according to tumour stage. To reduce the unmeasured bias associated with treatment, we performed an instrumental variable analysis.

• Stratified (by stage and LE) Cox regression and competing-risks regression analyses were generated for the prediction of OS and cancer-specific mortality, respectively.

RESULTS

• Among patients with <10 years of LE, most were treated with radiotherapy (49%) or observation (47%). Among patients with ≥10 years of LE, most received radiotherapy (49%), followed by RP (26%).

• In men with <10 years of LE, RP and radiotherapy were not different with respect to OS (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.45–1.48, P = 0.499). Conversely, in men with ≥10 years of LE, RP was associated with an improved OS compared with observation (HR: 0.59, 95% CI: 0.49–0.71, P < 0.001) and radiotherapy (HR: 0.66, 95% CI: 0.56–0.79, P < 0.001).

• Similar results were recorded in competing-risks regression analyses.

CONCLUSION

• In patients with an estimated LE ≥10 years at initial diagnosis, RP was associated with improved survival compared with radiotherapy and observation, regardless of disease stage.

Read Previous Articles of the Week

Editorial – Prostate cancer surgery vs radiation: has the fat lady sung?

February 26, 2014/by Tony Costello

The current article by Sun et al. [1] representing a number of institutions involved in prostate cancer treatment provision is thought-provoking and hypothesis-generating. The authors contention when mining Surveillance, Epidemiology and End Results data for 67 000 men who had localized prostate cancer between 1988 and 2005 is that those with a life expectancy >10 years had less likelihood of prostate cancer death when treated with surgery rather than by radiotherapy or being left to observation. The Scandinavians have already shown, in the randomized study by Hugosson et al. [2], that if you have your prostate cancer removed you have less likelihood of symptomatic local recurrence, lower likelihood of metastasis and progression, and a 29% reduced likelihood of prostate cancer death. The current study asks the question ‘Is radiation therapy less likely to provide a long-term cure for prostate cancer than surgery?’ and gives an answer in the affirmative.

The current paper, in its way, neatly encapsulates the contemporary angst generated in the community when prostate cancer screening, diagnosis and therapy are discussed. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial [3] allegedly shows no benefit from treatment over observation and contends perhaps that we surgeons and radiation oncologists are harm-workers, not life-savers. The PLCO has a 52% PSA contamination in its control arm [3]. That flawed trial compared screening with de facto screening and produced, in my view, a null hypothesis. How do we explain the paradox of a 44% reduction in prostate cancer-specific mortality between 1993 and 2009? How do we explain the disconnect between these trials and the facts? What do we do with the data not yet considered by the expert panels showing that early PSA testing at age <50 years is highly predictive of subsequent lethal prostate cancer? [4]

Clinicians are rapidly moving to an era of judicious risk assessment. This can only be done after biopsy is performed. We now frequently enrol patients with apparently indolent prostate cancer into surveillance protocols [5]. So the question should be ‘If the disease found on biopsy is moderate to high risk, and potentially lethal for that man, should we remove his prostate surgically or radiate it with intensity-modulated radiation therapy, brachytherapy, proton therapy, +/- hormone therapy?’.

As a surgeon I have an inherent dislike of combining hormone therapy in primary treatment. At least 50% of men in high-risk prostate cancer cohorts who receive radiation therapy also receive hormone therapy as adjuvant or neoadjuvant treatment [6]. Hormone therapy has a myriad of side effects. Even if the playing field was level between surgery and radiation therapy, the avoidance of hormone therapy as a first-line treatment gives surgery a seductive advantage.

The authors of the current report show a significant survival advantage in the cohort for surgery over radiation therapy and observation. There will never be a randomized trial between the two potentially curative treatment methods surgery and radiation. The scourge of commercial interest with spurious claims of superiority of one form of therapy over another, proton beam vs intensity-modulated radiation therapy, robotics vs high-intensity focused ultrasonography, means that we risk having our decisions regarding appropriate therapy formed by multibillion dollar technology companies with powerful marketing capacity. The current paper confirms what is self-evident: untreated localized prostate cancer can be lethal. Surgery and radiation therapy lower the morbidity and mortality from prostate cancer. Which is the better method of curative therapy is moot, but we do know that cure is very much predicated on the expertise and location of the practitioner.

We know mostly when and who to treat and what treatments work well. In my view, the prostate cancer testing debate resonates with the contemporary discussion about childhood immunization for infectious diseases. Some parents now, who clearly cannot remember the devastating epidemics of polio and other childhood illnesses, refuse to immunize their children. Prostate cancer practitioners who did not live in the quite recent era where the initial presentation of prostate cancer was bone metastasis +/− crush fracture to the vertebra and sometimes paraplegia, may be unknowingly steering us backwards.

At the recent 2013 AUA meeting, Adams et al. [7] reported on the fate of men not screened for prostate cancer, i.e. those men who presented with a PSA >100 ng/mL. There was a 3-year survival rate of 9.7%, a 19.7% cord compression rate and a 64% hospitalization rate. Those who do not learn the lessons of history are condemned to repeat them.

Anthony J. Costello
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

Read the full article

References

Sun M, Sammon JD, Becker A et al. Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation. BJU Int 2014; 113: 200–208
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