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

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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 Aljabery1,2,*, Ivan Shabo2,3,4, Hans Olsson2,5, Oliver Gimm2,6 and Staffan Jahnson1,2

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

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.

Read more articles of the week

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

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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

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

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

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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