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

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.

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

 

image_n_bju13127-fig-0001
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.

Editorial: Penis cancer management – insight into the future

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.

Simon Horenblas

 

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

 

References

 

 

 

3 Horenblas S, Jansen L, Meinhardt W, Hoefnagel CA, de Jong DNieweg OE. Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol 2000;
163: 1004

 

4 Djajadiningrat RS, Graa and NM, van Werkhoven E et al. Contemporary management of regional nodes in penile cancer-improvement of survival? J Urol 2014; 191: 6873

 

 

 

7 Visser O, Adolfsson J, Rossi S et al. Incidence and survival of rare urogenital cancers in Europe. Eur J Cancer 2012; 48: 45664

 

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

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

 

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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