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

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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

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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: LESS nephroureterectomy: is it a good alternative?

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video by Prof. Rha and colleagues of LESS nephroureterectomy.

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

Laparoendoscopic single-site nephroureterectomy for upper urinary tract urothelial carcinoma: outcomes of an international multi-institutional study of 101 patients

Sung Yul Park, Koon Ho Rha1, Riccardo Autorino2, Ithaar Derweesh3, Evangelos Liastikos4, Yao Chou Tsai5, Ill Young Seo6, Ugo Nagele7, Aly M. Abdel-Karim8, Thomas Herrmann9, Deok Hyun Han10, Soroush Rais-Bahrami11, Seung Wook Lee, Kyu Shik Kim, Paolo Fornara12, Panagiotis Kallidonis4, Christopher Springer12, Salah Élsalmy8, Shih-Chieh Jeff Chueh13, Chen-Hsun Ho14, Kamol Panumatrassamee2, Ryan Kopp3, Jens-Uwe Stolzenburg15, Lee Richstone11, Jae Hoon Chung, Tae Young Shin1, Francesco Greco12 and Jihad H. Kaouk2

Department of Urology, Hanyang University College of Medicine, Seoul, Korea, 1Department of Urology, Yonsei University College of Medicine, Seoul, Korea, 2Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA, 3Division of Urology, University of California San Diego, La Jolla, CA, USA, 4Department of Urology, School of Medicine, University of Patras, Patras, Greece, 5Division of Urology, Buddhist Tzu Chi General Hospital, TaipeiBranch, Taipei, Taiwan, 6Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, Korea, 7Department of Urology, LKH, Hall in Tirol, Austria, 8Department of Urology, Alexandria University, Alexandria, Egypt, 9Department of Urology, Hannover Medical School, Hannover, Germany, 10Department of Urology, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea, 11The Arthur Smith Institute for Urology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY, USA, 12Department of Urology and Kidney Transplantation, Martin-Luther-University, Halle/Saale, Germany, 13Cleveland Clinic Urology Charleston Office, Charleston, WV, USA, 14Division of Urology, National Taiwan University Hospital, Taipei, Taiwan, 15Department of Urology, University of Leipzig, Leipzig, Germany

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OBJECTIVE

• To report a large multi-institutional series of laparoendoscopic single-site (LESS) nephroureterectomy (NU).

MATERIALS AND METHODS

• Data on all cases of LESS-NU performed between 2008 and 2012 at 15 institutions were retrospectively gathered.

• The main demographic data and perioperative outcomes were analysed.

RESULTS

• The study included 101 patients whose mean (sd) age was 66.4 (9.9) years and mean (sd) body mass index was 24.8 (4) kg/m2, and of whom 29.7% had undergone previous abdominal/pelvic surgery.

• The mean (sd) operating time was 221.4 (73.7) min, estimated blood loss 231.7 (348.0) mL.

• A robot-assisted LESS technique was applied in 25.7% of cases. An extra trocar was inserted in 28.7% of cases to complete the procedure. Conversion to open surgery was necessary in three cases (3.0%). There was no bladder cuff excision in 20.8% of cases, and excision was carried out using a variety of techniques in the remaining cases.

• Six intra-operative complications occurred (5.9%). The mean (sd) length of hospital stay was 6.3 (3.5) days. The overall postoperative complication rate was 10.0%, and most of the complications were low grade (Clavien grades 1 and 2).

• The mean tumour size was 3.1 (1.9) cm. Pathological staging was pTis in two patients, pTa in 12 patients, pT1 in 42 patients, pT2 in 20 patients, pT3 in 23 patients and pT4 in two patients. Pathological grade was high in 71 and low in 30 patients.

• At a mean follow-up of 14 months, six patients (5.9%) had died. Disease recurrence (including distant and bladder recurrence) was detected in 22.8% of patients, with a mean time to recurrence of 11.5 months.

CONCLUSIONS

• This study reports the largest multi-institutional experience of LESS-NU to date.

• Peri-operative outcomes mirror those of published standard laparoscopy series.

• Despite encouraging early findings, longer follow-up is needed to determine the oncological efficacy of the procedure.

 

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Editorial: LESS versus laparoscopic nephroureterectomy: the winner is…

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In this international multi-institutional study, Park et al. [1] have retrospectively collected and analysed data about 101 patients who underwent laparoendoscopic single-site (LESS) nephroureterectomy (NU) for upper urinary tract (UUT) urothelial carcinoma.

Nowadays, NU represents the standard of care for the surgical treatment of UUT urothelial carcinoma in the majority of patients [2]. Outcomes of such an intervention are strongly improved when lymph node dissection (LND) is performed according to a well-defined template [3].

In recent years, laparoscopy has become an important new approach to reduce the invasiveness of the surgical treatment of UUT urothelial carcinoma. In a multicentre Italian study Porpiglia et al. [4] showed that laparoscopic NU with open ureterectomy was a feasible and safe technique. Oncological results seemed to be similar to those of the traditional open approach, but the laparoscopic approach still has some disadvantages. First, patients who undergo a laparoscopic procedure receive LND with lower frequency. Moreover, the template during a laparoscopic procedure is rarely respected and the number of lymph nodes removed is often suboptimal [3]. Second, there is no consensus in the literature about the pathological stages that could potentially benefit from the bladder-cuff excision step of this procedure [5]. Bladder-cuff excision omission does not seem to undermine survival in patients with low-stage (pT1-2) disease, nevertheless confirmatory recurrence data are required before a NU without bladder-cuff excision may be considered as an option for this patient category.

The present paper shows that advances in surgical technology are being made, but it also underlines the fact that the above-mentioned disadvantages of NU are still under discussion, and these disadvantages are expanded when introducing a newer and challenging technique such as the LESS approach.

In the present study, different devices and instruments were used. Furthermore, the rate of LND reported was very low (27%), as the number of lymph nodes removed (approximately five). LND was often ‘formally’ performed, and no specific template was reported to be used. Bladder-cuff excision was not performed in 20% of cases and, when performed, the technique used was not clearly defined. With regard to oncological efficacy, the recurrence rate of 22% at 11 months is not sufficient to clarify if the LESS approach is oncologically effective [6].

In summary, there are evident limitations to the present paper; some are methodological, such as its retrospective nature and the non-homogeneous datasheets used to collect data, and some are technical and oncological. These limitations are justified by the fact that the technique is in its embryonic stages. Nevertheless, the authors deserve praise for having collected such a large number of cases for their study on LESS NU. Their paper underlines the fact that this technique is feasible and safe, and each surgeon who contributed by insisting on such a challenging and novel approach to NU should be congratulated for their efforts.

Now that the feasibility of the LESS NU technique has been demonstrated, the authors have the task of clarifying whether introducing a LESS approach would or would not compromise oncological outcomes. In any case, it is recommended that surgical oncological principles be respected when a new technique is introduced, especially when dealing with a high-risk cell-seeding tumour such as urothelial carcinoma.

Francesco Porpiglia and Riccardo Bertolo
Department of Clinical and Biological Sciences, San Luigi Hospital, Division of Urology, University of Turin, Orbassano-Turin, Italy

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REFERENCES
  1. Park SY, Rha KH, Autorino R et al. Laparoendoscopic single-site nephroureterectomy for upper urinary tract urothelial carcinoma: outcomes of an international multi-institutional study of 101 patients. BJU Int 2013; 112: 610–615
  2. Rouprêt M, Zigeuner R, Palou J et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol 2011; 59: 584–594
  3. Roscigno M, Brausi M, Heidenreich A et al. Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer.Eur Urol 2011; 60: 776–783
  4. Porpiglia F, Celia A, Luciani L, Terrone C, Guazzoni G, Parma P. Laparoscopic radical nephroureterectomy: results of a multicentric italian study. J Endourol 2009; 23 (Suppl. 1): A109
  5. Lughezzani G, Sun M, Perrotte P et al. Should bladder cuff excision remain the standard of care at nephroureterectomy in patients with urothelial carcinoma of the renal pelvis? A population-based study. Eur Urol 2010; 57: 956–962
  6. Walton TJ, Novara G, Matsumoto K et al. Oncological outcomes after laparoscopic and open radical nephroureterectomy: results from an international cohort. BJU Int 2010; 108: 406–412

Video: Is LESS more when it comes to nephroureterectomy?

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Laparoendoscopic single-site nephroureterectomy for upper urinary tract urothelial carcinoma: outcomes of an international multi-institutional study of 101 patients

Sung Yul Park, Koon Ho Rha1, Riccardo Autorino2, Ithaar Derweesh3, Evangelos Liastikos4, Yao Chou Tsai5, Ill Young Seo6, Ugo Nagele7, Aly M. Abdel-Karim8, Thomas Herrmann9, Deok Hyun Han10, Soroush Rais-Bahrami11, Seung Wook Lee, Kyu Shik Kim, Paolo Fornara12, Panagiotis Kallidonis4, Christopher Springer12, Salah Élsalmy8, Shih-Chieh Jeff Chueh13, Chen-Hsun Ho14, Kamol Panumatrassamee2, Ryan Kopp3, Jens-Uwe Stolzenburg15, Lee Richstone11, Jae Hoon Chung, Tae Young Shin1, Francesco Greco12 and Jihad H. Kaouk2

Department of Urology, Hanyang University College of Medicine, Seoul, Korea, 1Department of Urology, Yonsei University College of Medicine, Seoul, Korea, 2Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA, 3Division of Urology, University of California San Diego, La Jolla, CA, USA, 4Department of Urology, School of Medicine, University of Patras, Patras, Greece, 5Division of Urology, Buddhist Tzu Chi General Hospital, TaipeiBranch, Taipei, Taiwan, 6Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, Korea, 7Department of Urology, LKH, Hall in Tirol, Austria, 8Department of Urology, Alexandria University, Alexandria, Egypt, 9Department of Urology, Hannover Medical School, Hannover, Germany, 10Department of Urology, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea, 11The Arthur Smith Institute for Urology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY, USA, 12Department of Urology and Kidney Transplantation, Martin-Luther-University, Halle/Saale, Germany, 13Cleveland Clinic Urology Charleston Office, Charleston, WV, USA, 14Division of Urology, National Taiwan University Hospital, Taipei, Taiwan, 15Department of Urology, University of Leipzig, Leipzig, Germany

Read the full article
OBJECTIVE

• To report a large multi-institutional series of laparoendoscopic single-site (LESS) nephroureterectomy (NU).

MATERIALS AND METHODS

• Data on all cases of LESS-NU performed between 2008 and 2012 at 15 institutions were retrospectively gathered.

• The main demographic data and perioperative outcomes were analysed.

RESULTS

• The study included 101 patients whose mean (sd) age was 66.4 (9.9) years and mean (sd) body mass index was 24.8 (4) kg/m2, and of whom 29.7% had undergone previous abdominal/pelvic surgery.

• The mean (sd) operating time was 221.4 (73.7) min, estimated blood loss 231.7 (348.0) mL.

• A robot-assisted LESS technique was applied in 25.7% of cases. An extra trocar was inserted in 28.7% of cases to complete the procedure. Conversion to open surgery was necessary in three cases (3.0%). There was no bladder cuff excision in 20.8% of cases, and excision was carried out using a variety of techniques in the remaining cases.

• Six intra-operative complications occurred (5.9%). The mean (sd) length of hospital stay was 6.3 (3.5) days. The overall postoperative complication rate was 10.0%, and most of the complications were low grade (Clavien grades 1 and 2).

• The mean tumour size was 3.1 (1.9) cm. Pathological staging was pTis in two patients, pTa in 12 patients, pT1 in 42 patients, pT2 in 20 patients, pT3 in 23 patients and pT4 in two patients. Pathological grade was high in 71 and low in 30 patients.

• At a mean follow-up of 14 months, six patients (5.9%) had died. Disease recurrence (including distant and bladder recurrence) was detected in 22.8% of patients, with a mean time to recurrence of 11.5 months.

CONCLUSIONS

• This study reports the largest multi-institutional experience of LESS-NU to date.

• Peri-operative outcomes mirror those of published standard laparoscopy series.

• Despite encouraging early findings, longer follow-up is needed to determine the oncological efficacy of the procedure.

Article of the week: Fit to a T-cell: measuring host immunity in renal cell carcinoma

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Dr. Scala discussing her article.

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

Regulatory T cells, interleukin (IL)-6, IL-8, Vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma

Marianeve Polimeno, Maria Napolitano, Susan Costantini*, Luigi Portella, Arianna Esposito, Francesca Capone*, Eliana Guerriero*, AnnaMaria Trotta, Serena Zanotta, Luigi Pucci†, Nicola Longo†, Sisto Perdonà‡, Sandro Pignata‡, Giuseppe Castello* and Stefania Scala

Oncological Immunology, National Cancer Institute ‘G. Pascale’, *National Cancer Institute ‘G. Pascale’ Cancer Research Center, Mercogliano, Avellino, †Genitourinary Oncology and Rare Cancer Center, Federico II University, ‡Department of Urology, National Cancer Institute ‘G. Pascale’, Naples, Italy

M.P. and M.N. contributed equally to this work.

Read the full article
OBJECTIVE

• To identify a phenotype that could be informative and prognostic in patients with renal cell carcinoma (RCC) peripheral blood was evaluated for TH1, TH2, regulatory T cells (Tregs), natural killer (NK) and NKT cells and for cytokines/chemokines.

PATIENTS AND METHODS

• Peripheral blood from 77 patients with RCC and 40 healthy controls was evaluated by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RA, CD45RO, CD152, CD184, CD279, CD3, CD16, CD56, CD161, CD158a, CD4, CD26, CD30, CD183 and CD184.

• A concomitant evaluation of 38 molecules was conducted in patients’ serum using a multiplex biometric ELISA-based immunoassay.

RESULTS

• The number of NK cells CD3−/CD16+, CD3−/CD16+/CD161+ (NK) and CD3−/CD16+/CD161+/CD158a+ (NK- Kir 2+) was greater in the patients with RCC (P < 0.05); and the number of Treg cells CD4+/CD25high+/FOXP3+ and the subset CD4+/CD25high+/FOXP3+/CD45RA+ (naïve) and CD45R0+(memory) cells, were greater in the patients with RCC (P < 0.001).

• An increase in the following was observed in the serum of patients with RCC compared with healthy controls: interleukin (IL)-4, IL-6, IL-8, IL-10, G-CSF, CXCL10, CXCL11, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). According to Ingenuity Pathway Analysis (IPA), CXCL10, IL-6, IL-8, epidermal growth factor (EGF), HGF and VEGF were associated with a network that controls cellular movement, tissue development and cellular growth.

• Kaplan–Meier analysis for disease-free survival showed that high numbers of CD4+/CD25high+/FOXP3+/CD45RA+ (Treg naïve) and low numbers of CD3−/CD16+/CD161+/CD158a+ (NK-Kir+) cells predict short disease-free survival in patients with RCC.

CONCLUSION

• Concomitant evaluation of Treg (CD4+/CD25high+/FOXP3+ and CD4+/CD25high+/FOXP3+/CD45RA+) and of six soluble factors (IL-6, IL-8 ,VEGF, CXCL10, CXCL11, EGF, HGF) might be a surrogate marker of host immunity in patients with RCC.

 

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Editorial: Regulatory T cells in renal cell carcinoma: additional fuel to the bonfire of debate

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In the developing immune system, all T cells are positively selected in the neonatal thymus for the ability to recognize self-antigens, the major histocompatibility complex (MHC) proteins. Thus, the mature T-cell repertoire is trained to ‘see’ foreign pathogens ‘complexed’ with those self-antigens (‘MHC-presentation’). Fundamentally, this requirement predisposes mammalian systems to the development of autoimmune diseases, as all T cells are self-reactive. That such diseases are the exception rather than the rule is attributable to a small population (∼2–5%) of circulating T cells, termed ‘regulatory T cells’ (Tregs), that suppress the activation and function of many other immune cells. The fine balance between Tregs and other pro-inflammatory cells is essential for maintaining self-tolerance while allowing immunological reactivity against danger signals such as foreign antigens (mostly pathogens) and malignant cells. Many pathogens co-evolving alongside the mammalian immune system have learned to ‘hijack’ this balance to propagate disease or to inhibit their own clearance, notably Leishmaniasis, malaria, tuberculosis, HIV, hepatitis C virus and Helicobacter pylori. In these scenarios, an excess of Tregs induced by the pathogens prevents their clearance and establishes infective chronicity.

Likewise, in malignant diseases, such as pancreatic and ovarian cancer, an excess of Tregs is thought to contribute to failure of the immune system to clear neoplastic cells. Whether the tumour environment appropriates the regulatory function of Tregs to propagate its own survival in a manner akin to infectious agents, or whether Tregs infiltrate larger tumours in which there is more chronic inflammation is unclear. Nevertheless, a correlation between higher Treg numbers and poorer outcomes is a common feature of malignancies. In this issue of the BJUI Polimeno et al. add evidence to the debate over whether Treg numbers in RCC are associated with worse outcomes. While previous publications both support (Cancer Immunol Immunother 2007, BJU Int 2009) and refute (Clin Cancer Res 2007) this assertion, the data presented by Polimeno et al. identify not only increased circulating Treg numbers in patients with RCC but also find an association betweenTreg numbers, especially those that express the naïve T-cell marker CD45RA, and both larger tumour load and worse prognosis. In the same dataset, as expected, the authors also find that a shorter disease-free survival was evident in patients with lower numbers of tumoricidal natural killer cells. In the serum, patients with RCC had higher concentrations of soluble factors involved in cell growth and movement, such as epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor and interferon γ-induced protein 10 (also known as CXCL10), and markers of active inflammation, such as interleukins 6 and 8.

These observations suggest several broad possibilities: (i) that the ‘Tregs’ identified in the tumour environment and circulation are not Tregs but are in fact other activated T cells that temporarily express the same surface markers as bona fide Tregs; (ii) that Tregs in the context of RCC are unable to control tumour-associated inflammation; (iii) that Tregs contribute to tumour survival by inhibiting clearance of neoplasms by other immune cells, resulting in chronic inflammation; and/or (iv) that Tregs are actively contributing to the inflammation by converting to pro-inflammatory phenotypes, as has been demonstrated by several groups. These possibilities can be differentiated by isolating Tregs from the tumour environment or local draining lymph nodes and testing their functional characteristics in vitro; however, the fact that CD45RA+ Tregs were independently associated with worse outcomes makes (i) and (ii) less likely, as such cells are less likely to be recently activated and are inherently less plastic than other populations of Tregs.

In our opinion, the clinical value of the data presented in this paper and those of others, even if the underlying biology is poorly understood, should next be determined in a prospective study to see whether the immunological ‘fingerprint’ in peripheral blood can correctly identify those patients who are more likely to do poorly, targeting them for closer monitoring and/or more aggressive therapy.

Behdad Afzali and Giovanna Lombardi
Medical Research Council Centre for Transplantation, King’s College London, King’s Health Partners, Guy’s Hospital, and National Institute for Health Research Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, Guy’s Hospital, London, UK

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Video: Host immunity in renal cell carcinoma: call on the Tregs

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Regulatory T cells, interleukin (IL)-6, IL-8, Vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma

Marianeve Polimeno, Maria Napolitano, Susan Costantini*, Luigi Portella, Arianna Esposito, Francesca Capone*, Eliana Guerriero*, AnnaMaria Trotta, Serena Zanotta, Luigi Pucci†, Nicola Longo†, Sisto Perdonà‡, Sandro Pignata‡, Giuseppe Castello* and Stefania Scala

Oncological Immunology, National Cancer Institute ‘G. Pascale’, *National Cancer Institute ‘G. Pascale’ Cancer Research Center, Mercogliano, Avellino, †Genitourinary Oncology and Rare Cancer Center, Federico II University, ‡Department of Urology, National Cancer Institute ‘G. Pascale’, Naples, Italy

M.P. and M.N. contributed equally to this work.

Read the full article
OBJECTIVE

• To identify a phenotype that could be informative and prognostic in patients with renal cell carcinoma (RCC) peripheral blood was evaluated for TH1, TH2, regulatory T cells (Tregs), natural killer (NK) and NKT cells and for cytokines/chemokines.

PATIENTS AND METHODS

• Peripheral blood from 77 patients with RCC and 40 healthy controls was evaluated by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RA, CD45RO, CD152, CD184, CD279, CD3, CD16, CD56, CD161, CD158a, CD4, CD26, CD30, CD183 and CD184.

• A concomitant evaluation of 38 molecules was conducted in patients’ serum using a multiplex biometric ELISA-based immunoassay.

RESULTS

• The number of NK cells CD3−/CD16+, CD3−/CD16+/CD161+ (NK) and CD3−/CD16+/CD161+/CD158a+ (NK- Kir 2+) was greater in the patients with RCC (P < 0.05); and the number of Treg cells CD4+/CD25high+/FOXP3+ and the subset CD4+/CD25high+/FOXP3+/CD45RA+ (naïve) and CD45R0+(memory) cells, were greater in the patients with RCC (P < 0.001).

• An increase in the following was observed in the serum of patients with RCC compared with healthy controls: interleukin (IL)-4, IL-6, IL-8, IL-10, G-CSF, CXCL10, CXCL11, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). According to Ingenuity Pathway Analysis (IPA), CXCL10, IL-6, IL-8, epidermal growth factor (EGF), HGF and VEGF were associated with a network that controls cellular movement, tissue development and cellular growth.

• Kaplan–Meier analysis for disease-free survival showed that high numbers of CD4+/CD25high+/FOXP3+/CD45RA+ (Treg naïve) and low numbers of CD3−/CD16+/CD161+/CD158a+ (NK-Kir+) cells predict short disease-free survival in patients with RCC.

CONCLUSION

• Concomitant evaluation of Treg (CD4+/CD25high+/FOXP3+ and CD4+/CD25high+/FOXP3+/CD45RA+) and of six soluble factors (IL-6, IL-8 ,VEGF, CXCL10, CXCL11, EGF, HGF) might be a surrogate marker of host immunity in patients with RCC.

Article of the week: The AUA speaks: prostate cancer detection guideline

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

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

American Urological Association (AUA) Guideline on prostate cancer detection: process and rationale

H. Ballentine Carter

The Johns Hopkins University School of Medicine, Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA

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ABSTRACT

To review the process and rationale for the American Urological Association (AUA) guideline on prostate cancer detection. The AUA guideline on detection of prostate cancer involved a systematic literature review of >300 studies that evaluated outcomes important to patients (prostate cancer, incidence/mortality, health-related quality of life, diagnostic accuracy and harms of testing). A multidisciplinary panel interpreted the evidence and formulated statements to assist the urologist and the asymptomatic average-risk man in decision-making about prostate cancer detection. Other than prostate-specific antigen (PSA)-based prostate cancer screening, there was no evidence to address the outcomes of interest to patients. The strongest evidence that benefits may outweigh harms was in men aged 55–69 years undergoing PSA-based screening. This led the panel to recommend shared decision-making for these men at average risk, but recommend against routine screening for other age groups at average risk. Further, to reduce the harms associated with screening (false positive tests, over diagnosis, over treatment), the panel recommended against annual screening for those who choose to be screened. A panel under the auspices of the AUA recommended shared decision-making for the average risk asymptomatic man aged 55–69 years considering PSA-based screening for prostate cancer detection.

 

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Article of the week: Radiation-recurrent prostate cancers are often multifocal

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

This week, we feature two Articles of the Week.

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.

The final post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video by Dr. de Castro Abreu and colleagues.

Accuracy of post-radiotherapy biopsy before salvage radical prostatectomy

Joshua J. Meeks, Marc Walker*, Melanie Bernstein, Matthew Kent† and James A. Eastham

Urology Service, Department of Surgery and †Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY, and *Department of Surgery, Urology Service, Tripler Army Medical Center, Honolulu, HI, USA

Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers.

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OBJECTIVE

• To determine whether post-radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer.

PATIENTS AND METHODS

• SRP was performed between 1998 and 2011 on 198 patients.

• All patients underwent a PRB. PRB and SRP specimens were evaluated by a genitourinary pathologist. Patients had external-beam RT alone (EBRT; 71%) or brachytherapy with or without EBRT (29%).

RESULTS

• Of the men undergoing SRP, 26 (14%) were clinical stage ≥T3, with 13% of PRBs with Gleason score ≥8.

• Cancer was unilateral in 120 (61%) biopsies, with contralateral or bilateral prostate cancer at SRP in 49%. In the SRP specimen, cancer was multifocal in 57%.

• Cancer was upgraded at SRP in 58% of men, with 20% having an increase in primary Gleason grade.

• The accuracy of PRB varied by region from 62% to 76%, with undetected cancers ranging from 12% to 26% and most likely to occur at the mid-gland.

CONCLUSIONS

• Radiation-recurrent prostate cancers were often multifocal, and biopsy missed up to 20% of tumours.

• More than half of the cancers were upgraded at SRP, and many that were unilateral on PRB were bilateral at SRP.

 

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Article of the week: Salvage focal or total cryoablation after failed primary radiotherapy: which is better?

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

This week, we feature two Articles of the Week.

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.

The final post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video by Dr. de Castro Abreu and colleagues.

Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy

Andre Luis de Castro Abreu*, Duke Bahn*†, Scott Leslie*, Sunao Shoji*, Paul Silverman†, Mihir M. Desai*, Inderbir S. Gill* and Osamu Ukimura*

*USC Institute of Urology, Hillard and Roclyn Herzog Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los Angeles, and †Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA

Read the full article
OBJECTIVES

• To present the oncological and functional outcomes of salvage focal (SFC) and salvage total (STC) cryoablation for recurrent prostate cancer (PCa) after failed primary radiotherapy.

PATIENTS AND METHODS

• From March 2003 to August 2010, 50 men with biopsy-proven unilateral (n = 25) or bilateral (n = 25) radio-recurrent PCa underwent SFC or STC, respectively.

• Patients were assessed after treatment by prostate-specific antigen (PSA) testing, transrectal ultrasonography, biopsy and questionnaires. Biochemical failure (BF) was defined using the Phoenix criteria (PSA nadir + 2 mg/mL).

• Data were prospectively collected and retrospectively analysed.

RESULTS

• The median pre-cryoablation PSA level and Gleason score were, respectively, 2.8 ng/mL and 7 for SFC, and 3.9 ng/mL and 7 for STC. The median follow-up was 31 and 53 months (P = 0.004) for SFC and STC, respectively.

• Oncological outcomes were as follows: no patient died; one patient who underwent STC developed bone metastases; eight patients who underwent SFC and three who underwent STC had BF and the 5-year BF-free survival rates were 54 and 86%, respectively. In those patients without BF, the mean PSA decreased by 86% for SFC and 90% for STC within the first year and remained stable.

• Functional outcomes were as follows: new onset urinary incontinence occurred in three (13%) patients in the STC group, whereas no patient in the SFC group developed incontinence (P = 0.10); Two of seven patients in the SFC group retained postoperative potency, but none of the four potent patients in the STC group recovered potency postoperatively (P = 0.48); one (4%) patient in the STC group developed a recto-urethral fistula, but none occurred in the SFC group (P = 0.48).

CONCLUSIONS

• SFC and STC are feasible and safe with acceptable mid-term oncological outcomes. For carefully selected patients, SFC is an option that could be associated with lower treatment-related morbidity compared with STC.

• Although longer follow-up and more patient numbers are needed, our initial oncological and functional outcomes of SFC and STC are encouraging.

 

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