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Article of the Week: Detecting SNs in patients with BCa intra-operatively

September 13, 2017/by admin Z.9

Every Week the Editor-in-Chief selects an 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.

Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study

Firas Aljabery^1,2,*, Ivan Shabo^2,3,4, Hans Olsson^2,5, Oliver Gimm^2,6 and Staffan Jahnson^1,2

¹Department of Urology, Region Östergötland, Linköping University Hospital, Linköping, Sweden, ²Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, sweden ³Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden ⁴Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden ⁵Department of Pathology, Region Östergötland, Linköping University Hospital, Linköping, Sweden ⁶Department of Surgery, Region Östergötland, Linköping University Hospital, Linköping, Sweden

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Abstract

Objectives

To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

Patients and Methods

We studied 103 patients with BCa pathological stage T1–T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005–2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

Results

The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1–12 (12%), T2–20 (19%), T3–48 (47%) and T4–23 (22%). A mean (range) number of 31 (7–68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

Conclusion

We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

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Editorial: Positive messages for bladder cancer management in negative sentinel lymph node study

September 13, 2017/by admin Z.9

I encourage you to read the study by Aljabery et al. [1] in this edition of BJUI. Their findings are based on some very solid methodology and I think provide a robust answer to their question, which often in science means a ‘negative’ result. The principle of sentinel lymph node biopsy (SLNB) needs no introduction. It is primarily intended to detect the principal LN draining a tumour, allowing its removal and pathological determination of LN metastasis status in that individual [2].The avoidance of an unnecessary LN dissection (LND) and its associated risks is at the heart of any SLNB strategy. On the other hand, particularly for bladder cancer, there is a recognition that a higher number of LNs removed at the time of surgery confers a survival advantage to patients through more accurate staging [3]. With greater numbers of LNs removed pN0 patients are more likely to be truly N0 and pN1 patients with limited metastases have a greater chance that all disease has been completely excised. Thus, when considering SLNB in bladder cancer there is the usual conflict between maximising oncological benefit and minimising surgical harm.Aljabery et al. [1] present an excellent series of cystectomies with a 100% negative margin rate and mean LN count of 30. The 40% rate of LN involvement, is perhaps partly due to the meticulous triple sectioning of each excised LN. Their SLN technique involved four cystoscopic injections to the bladder wall surrounding the tumour and focused on the biggest lesion in multiple tumour cases. The LNs were removed in their packets and studied after removal from the patient. While this is likely to be a more precise method for determining the site of the SLN, it clearly differs from the approach one would take if trying to avoid LND in negative-SLN cases. Furthermore, examination of LNs was performed after formalin fixation. Typically when using SLN techniques frozen sections are also used to guide surgeons during surgery.The results clearly show that SLNB using radiolabelled nanocolloid does not allow accurate identification of pathologically LN-negative patients who could then avoid a complete LN dissection. Sensitivity of the technique in the detection of positive LNs ranged from 67% to 90% at the various LN stations. Overall, of patients with an identifiable SLN that was negative, 19% of patients had positive LNs elsewhere (81% negative predictive value). Effectively one in five patients who might be reassured by a negative SLN result would in fact have undetected positive LNs left behind if this technique were employed. Furthermore, this estimation does not consider errors likely to be introduced with in situ SLN identification and the use of frozen-section analysis rather than non-time-critical analysis of formalin-fixed sections.In such a dangerous disease such inaccuracy is not tolerable and so I totally agree with the authors’ [1] findings that SLNB of pelvic LNs at the time of radical cystectomy for bladder cancer is not a reliable technique for identifying LN metastasis.The positive messages from this study [1] are worth noting by those learning and undertaking cystectomy. The authors’ meticulous approach to surgery is evident from the methodology described and the accumulation of such a well-characterised series. This must be a contributing factor in achieving a 100% negative surgical margin rate and such consistently high LN yields. This should certainly be the aim of all cystectomists. The appropriate time, skill and patience should be given to this step and it should not be compromised upon, particularly when developing robot-assisted or laparoscopic cystectomy services.The findings that T-stage, N-stage and lymphovascular invasion are linked to survival are not that surprising. However, the use of LN metastatic density as a prognostic marker is interesting, as it is not usually discussed in our multidisciplinary meetings. This measure incorporates nodal tumour burden and the extent of LND. The finding of better outcomes in those with a LN metastatic density of <8% reinforces the message that even in those with LN metastases, removing greater numbers of LNs may improve prognosis. Furthermore, the finding that 30% of unilateral LN-positive tumours also had contralateral LNs settles any arguments for unilateral LN dissections.In a recent systematic review of SLNB in bladder cancer [4], the negative predictive value was found to be 92% compared to 81% in the Aljabery et al. [1] study. The authors of the systematic review suggested that SLNB is a promising technique; perhaps in view of technology advances they reviewed that might improve future outcomes of SLNB. While improvements may be possible, current evidence would not encourage me to consider SLNB using radiolabelled nanocolloid for fear of impairing cancer outcomes.

Congratulations to Aljabery et al. [1] on their work. I hope you find reading their paper as constructive as I did.

Tim Dudderidge
Department of Urology, University Hospital Southampton,
Southampton, Hampshire, UK

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References

1 Aljabery F, Shabo I, Olson H, Gimm O, Jahnson S. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study. BJU Int 2017; 120: 329–36

2 Gould EA, Winship T, Philbin PH, Kerr HH. Observations on a “sentinel node” in cancer of the parotid. Cancer 1960; 13: 77–8

3 Koppie TM, Vickers AJ, Vora K, Dalbagni G, Bochner BH. Standardization of pelvic lymphadenectomy performed at radical cystectomy. Cancer 2006; 107: 2368–74

4 Liss M, Noguchi J, Lee H, Vera D, Kader AK. Sentinel lymph node biopsy in bladder cancer: systematic review and technology update. Indian J Urol 2015; 31: 170–5

Video: Detecting SNs in patients with BCa intra-operatively

September 13, 2017/by admin Z.9

Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study

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Abstract

Objectives

Patients and Methods

Results

Conclusion

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Article of the Week: DSNB for Penile Cancer

June 15, 2016/by admin Z.9

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

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols

Panagiotis Dimopoulos*, Panagiotis Christopoulos*, Sam Shilito†, Zara Gall*‡, Brian Murby§, David Ashworth§, Ben Taylor, Bernadette Carrington, Jonathan Shanks**, Noel Clarke*, Vijay Ramani*, Nigel Parr*, Maurice Lau* and Vijay Sangar*

Departments of *Urology, §Nuclear Medicine, ¶Radiology , **Pathology, The Christie Hospital, Manchester, †Medical School, University of Manchester, Manchester, and ‡Department of Urology, Royal Bolton Hospital, Bolton Lancashire, UK

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Objective

To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer.

Patients and Methods

This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien–Dindo grading system).

Results

In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien–Dindo Grade 1–2.

Conclusions

DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

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Editorial: One Day Protocol for Early Penile Cancer – The Way to Go

June 15, 2016/by Paul Hegarty

The present article by Dimopoulos et al. [1] has some useful lessons on the development of new services. The authors have kept a detailed database of all patients going through their super-regional network, and have designed the protocol around the patient, whereby the primary and regional lymph nodes are dealt with in one visit. Previously, bilateral inguinal lymph node dissection (ILND) was so fraught with complications that it would not be combined routinely with organ-sparing surgery of the penis [2]; however, the significantly lower complication rate of dynamic sentinel node biopsy (DSNB) has allowed the more streamlined approach. The ‘only handle it once’ (OHIO) philosophy is surely not only preferable for the patient, but also reduces the risk of patients not receiving ideal management. In most cases, a biopsy at the time of presentation, along with physical examination/imaging, can determine those requiring DSNB instead of waiting for final pathology from the primary tumour. The controversy surrounding DSNB compared with ILND has been the false-negative rates. The pioneering group from the Netherlands reported four deaths in six patients with false-negative results [3]. In the present paper, the overall false-negative rate was 5.8%, but the smaller and newer cohort of patients underwent a same-day protocol and had zero false-negatives. This may be attributable to the fact that biopsies were taken from a total sample of 65 or that slightly more nodes were taken in this group. We expect the one-day protocol to become standard, and future independent reports will be welcome. Should there truly be a 0% false-negative rate then the controversy is resolved and prophylactic ILND will become a historical procedure. Finally, the lower morbidity of the present study cohort allowed the authors to move the intermediate-risk group from surveillance to nodal biopsy, which proved justified because some of these cases had micrometastatic disease. We congratulate the group for their scientific approach to improving the quality of care for patients and for bringing their data to publication.

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Paul K. Hegarty and Peter E. Lonergan

Urology, National Penile Cancer Centre, Mater Misericordiae University Hospital, Dublin, Ireland

References

1 Dimopoulos P, Christopoulos P, Shilito S et al. Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols. BJU Int 2016; 117: 890–6

2 Hegarty PK, Eardley I, Heidenreich A et al. Penile cancer: Organ-sparing techniques. BJU Int 2014; 114: 799–805

3 Kroon BK, Horenblas S, Meinhardt W et al. Dynaminc sentinel node biopsy in penile cancer: evaluation of 10 years experience. Eur Urol 2005; 47: 601–6

Article of the Month: DaPeCa-1 – Diagnostic Accuracy of SNB in Penile Cancer

February 3, 2016/2 Comments/by admin Z.9

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

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

DaPeCa-1: Diagnostic Accuracy of Sentinel Node Biopsy in 222 Penile Cancer Patients at four Tertiary Referral Centres — a National Study from Denmark

Jakob K. Jakobsen*, Kim P. Krarup†, Peter Sommer†, Henrik Nerstrøm†, Vivi Bakholdt‡, Jens A. Sørensen‡, Kasper Ø. Olsen*, Bjarne Kromann-Andersen§, Birgitte G. Toft¶, Søren Høyer**, Kirsten Bouchelouche†† and Jørgen B. Jensen*

*Departments of Urology, **Pathology, ††Nuclear Medicine and PET-Centre, Aarhus University Hospital, Aarhus, †Departments of Urology, ¶Pathology, Copenhagen University Hospital, Copenhagen, ‡Department of Plastic Surgery, Odense University Hospital, Odense, and §Department of Urology, Herlev University Hospital, Herlev, Denmark

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OBJECTIVES

To estimate the diagnostic accuracy of sentinel lymph node biopsy (SNB) in patients with penile cancer and assess SNB complications in a national multicentre setting.

PATIENTS AND METHODS

Retrospectively data were collected from records in four university centres by one medical doctor covering all SNBs performed in Denmark between 1 January 2000 and 31 December 2010. Patients had either impalpable lymph nodes (LNs) in one or both groins, or had a palpable inguinal mass from which aspiration cytology failed to reveal malignancy. Patients were injected with nanocolloid technetium and had a scintigram recorded before the SNB. The primary endpoint was LN recurrence on follow-up. The secondary endpoint was complications after SNB. Diagnostic accuracy was computed.

RESULTS

In all, 409 groins in 222 patients were examined by SNB. The median (interquartile range) follow-up of patients who survived was 6.6 (5–10) years. Of 343 negative groins, eight were false negatives. The sensitivity was 89.2% (95% confidence interval 79.8–95.2%) per groin. Interestingly, four of 67 T1G1 patients had a positive SNB. In all, 28 of 222 (13%) patients had complications of Clavien-Dindo grade I–IIIa.

CONCLUSION

Penile cancer SNB with a close follow-up stages LN involvement reliably and has few complications in a national multicentre setting. Inguinal LN dissection was avoided in 76% of patients.

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Editorial: Penis cancer management – insight into the future

February 3, 2016/by Simon Horenblas

The report of Jakobson et al. [1] assesses the results of the sentinel node procedure for penis carcinoma in Denmark. The sentinel node procedure was done in four university hospitals. In this geographically small country with little more than 5.6 million inhabitants and a case load of 50 patients with penis cancer per year, a distribution of care of patients with penis cancer over four hospitals seems reasonable at first sight.

The results show interesting elements. With a false-negative rate of 10.8%, the figure is in accordance with what is known from other series, albeit at the high end of the range [2]. The authors rightly acknowledge that there is room for improvement. It seems likely that centralising the procedure to two hospitals, as of 2009, will be instrumental in this endeavour.

The authors did not find a learning curve, underscoring the safe introduction of this procedure.

The experience testifies to the reliability of the procedure with a minimum of complications and morbidity. Despite inter-institutional variation no major differences were detected. The authors conclude that 76% of node dissections could be avoided.

More than 15 years after the first publication on the sentinel node procedure in a urological cancer, the debate on how to manage clinically node-negative patients is still not completely settled and the sentinel node procedure in penis cancer is not universally accepted [3].

Why?

There has been no randomised study comparing standard inguinal lymph node dissection to the sentinel node procedure. Comparisons of series with standard node dissection vs the sentinel node procedure have shown improved survival for the latter [4]. Nevertheless, in the absence of randomisation these figures have not convinced the whole urological community.

Advocates of the sentinel node procedure tend to emphasise the avoidance of unnecessary inguinal node dissections. Opponents tend to emphasise the false-negative rates with its ensuing risk of seriously jeopardising the patients, as some of the patient die from disease.

Oncological care has to seek the most rational balance between too much and too little, realising that 100% success does virtually not exist. It is reasonable to assume that if all elements of the chain necessary to deliver state-of-the-art treatment of penis cancer, the figures of false-negative sentinel node procedures should be around 4–5%. With meticulous follow-up, recurrences should be detected at the earliest possible moment, decreasing the risk of a fatal outcome. A 5% risk is a generally accepted figure to avoid a potentially harmful procedure. New tracers give hope that false-negative rates can even be improved, realising again that some failures have to be accepted as a fact of life [5, 6].

Opponents point to the technicalities of the procedure. True as it is, there is no modern hospital without all the equipment and the expertise, accumulated in other areas in oncology, necessary to perform a state of the art sentinel node procedure.

Is there reluctance to refer patients with penis cancer or is there a strong reason to rely on inguinal node dissection only? There can hardly be a financial motive considering the rarity of the disease. Is it fear for degradation of the trade by losing another surgical procedure, infringement of the surgical ego?

The management of penis cancer is exemplary for changes in health care. While initially four university hospitals were involved, this is further scaled down to two hospitals. Earlier in the Netherlands, the management of >75% of the patients with penis cancer in one institution led to the highest survival of these patients worldwide (88.3%) [7].

Introduction of a new procedure in medicine has to date been a more or less individual effort. This will be of the past with current health policy and a wealth of data on the effect of centralisation. A central introduction of a new procedure in a limited number of institutions and more rational distribution of care with dedicated professionals in institutions suited for the procedure will be the rule.

The future of lymph node staging looks bright for any urological cancer. There will be a day where discussions on sentinel node and the extent of the dissection will be of the past. Our successors will look with bewilderment at our discussions on sentinel node, extended, super-extended or minimal dissections and the failures to grasp the exact mechanisms of lymphatic invasion and the true role of surgical removal. Imaging methods will give unprecedented insight in nodes invaded by tumour. Smart molecules will kill specifically nodal metastases and will revert the process of lymphangiogenesis enhanced by effective immunotherapy.

But before we see these times, the treatment of patients with penis cancer will be completely centralised worldwide to the benefit of these patients.

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Simon Horenblas

Department of Urology, Netherlands Cancer Institute, Antonivan Leeuwenhoek Hospital, Amsterdam, The Netherlands

References

1 Jakobsen JK, Krarup KP, Sommer P et al. DaPeCa-1: diagnostic accuracy of sentinel lymph node biopsy in 222 patients with penile cancer at four tertiary referral centres – a national study from Denmark. BJU Int 2015; 117: 235–43

2 Sadeghi R, Gholami H, Zakavi SR, Kakhki VR, Tabasi KT, Horenblas S. Accuracy of sentinel lymph node biopsy for inguinal lymph node staging of penile squamous cell carcinoma: systematic review and meta-analysis of the literature. J Urol 2012; 187: 25–31

3 Horenblas S, Jansen L, Meinhardt W, Hoefnagel CA, de Jong D, Nieweg OE. Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol 2000;

163: 100–4

4 Djajadiningrat RS, Graa ﬂand NM, van Werkhoven E et al. Contemporary management of regional nodes in penile cancer-improvement of survival? J Urol 2014; 191: 68–73

5 Brouwer OR, van den Berg NS, Matheron HM et al. A hybrid radioactive and ﬂuorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. Eur Urol 2014; 65: 600–9

6 Brouwer OR, van den Berg NS, Matheron HM et al. Feasibility of intraoperative navigation to the sentinel node in the groin using preoperatively acquired single photon emission computerized tomography data: transferring functional imaging to the operating room. J Urol 2014; 192: 1810–6

7 Visser O, Adolfsson J, Rossi S et al. Incidence and survival of rare urogenital cancers in Europe. Eur J Cancer 2012; 48: 456–64

Video: DaPeCa-1 – Diagnostic Accuracy of SNB in Penile Cancer

February 3, 2016/by admin Z.9

DaPeCa-1: Diagnostic Accuracy of Sentinel Node Biopsy in 222 Penile Cancer Patients at four Tertiary Referral Centres — a National Study from Denmark

Read the full article

OBJECTIVES

To estimate the diagnostic accuracy of sentinel lymph node biopsy (SNB) in patients with penile cancer and assess SNB complications in a national multicentre setting.

PATIENTS AND METHODS

RESULTS

CONCLUSION

Penile cancer SNB with a close follow-up stages LN involvement reliably and has few complications in a national multicentre setting. Inguinal LN dissection was avoided in 76% of patients.

Read more articles of the week