Correspondence
Effective maybe, but is it cost-effective? A reply DOI: 10.1111/his.12438 © 2014 John Wiley & Sons Ltd.
Sir: The letter from Varma and Griffiths in response to our study that investigated lymph node yield following processing of all tissues submitted from lymph node dissections in association with radical prostatectomy for prostate adenocarcinoma1 suggests that this should not be undertaken, on the basis of costeffectiveness. In the letter, the authors query how many additional blocks were required for the complete processing of lymphadenectomy tissues. No evidence-based guidelines for the sampling of these tissues currently exist. In our study, we identified palpable lymph nodes and then embedded the tissue completely. This necessitated the preparation of an additional three to five blocks per case. With a mean of 7.4 blocks per case, total embedding of lymphadenectomy tissue resulted in the detection of an additional 190% of lymph nodes.1 Varma and Griffiths make the point that a section taken through a lymph node may miss micrometastases. In support of this, they cite their unpublished study from 2007, which evaluated the utility of frozen sections of pelvic lymph nodes obtained during radical prostatectomy. They showed that frozen sections revealed metastatic tumour in 2% of cases, with a false-negative result being obtained in 3% of cases, following submission of the entire node for paraffin processing. Similar results were reported more than a decade earlier, when it was shown that frozen section assessment of lymph nodes for prostate cancer had a sensitivity of only 63.2%.2 These observations are not relevant to our study, as the majority of impalpable nodes are of small size, and sectioning therefore samples a substantial proportion of the node. There are no firm recommendations suggesting an optimum nodal harvest for patients undergoing radical prostatectomy for prostate cancer. In a postmortem study, it was shown that the mean number of lymph nodes removed during bilateral lymph node dissection was 22.7.3 This was similar to the mean number of 20.5 lymph nodes removed from patients undergoing radical prostatectomy. The authors noted that ~20 pelvic lymph nodes may serve as a guideline for sufficient standard pelvic lymph node dissection. It is of interest that, in support of these findings, total processing of our specimens resulted in the detection Histopathology, 65, 722–730.
729
of a mean number of 10.8 nodes per side. This indicates that total submission of pelvic lymphadenectomy tissue provides evidence of the adequacy of lymphadenectomy. In their letter, the authors query our ability to accurately identify and count the numbers of lymph nodes present. In reality, the technique that we employ makes this straightforward. First, as noted above, the impalpable nodes discovered following complete sampling are small, and are therefore well circumscribed and easily identified as discrete nodes. Second, we embed the lymphadenectomy specimen in serial blocks, and this makes it possible to match a partially sampled node in one block with the other portion of it in the adjacent block. The presence of metastases in lymph nodes is of prognostic significance for prostate cancer. In particular, it has been shown that both the maximum diameter of nodal metastases and the grade of nodal tumour are independent predictors of outcome on multivariate analysis.4 This underscores the importance of total submission of lymphadenectomy specimens. In our study, we identified additional metastatic prostatic cancer in 7.3% of cases, thus permitting more accurate assignment of tumour grade to lymph node metastases. In their concluding comments, Varma and Griffiths muse that it might be possible for additional lymph nodes to be be detected in other malignancies following submission of all tissues removed as part of a curative resection for cancer in a variety of organs. In this context, they particularly mention axillary lymph node dissections and colectomies. This latter argument is inappropriate, as the authors are confusing practicality and feasibility with cost-effectiveness. There are protocols in place to ensure optimum sampling of relevant nodes for patients with breast and rectal cancer, and these have been well validated.5–7 Such protocols remain to be established for prostate cancer; hence the purpose of our study. Varma and Griffiths conclude that processing of lymphadenectomy tissue is not cost-effective, and here their argument is on shaky ground. Although the data that we reported were from a formal study based on the material submitted to a solitary, specialized, private uropathology practice, in the three pathology units (one hospital and two private pathology practices) in which the authors work, all lymphadenectomy tissue are always routinely embedded, as this provides optimal prognostic information for the surgeon and also accurately informs subsequent treatment. The additional sections that are examined as a result of this are small and the costs
730
Correspondence
are trivial in relation to the total cost of the procedure and subsequent care. Joanna Perry-Keene1,2 Peter Ferguson3,4 Hemamali Samaratunga1 John N Nacey5 Brett Delahunt4 Aquesta Uropathology, 2Royal Brisbane Hospital, Brisbane, Qld, Australia, 3Wellington School of Medicine and Health Sciences, Malaghan Institute of Medical Research, University of Otago, 4Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, and 5 Department of Surgery, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand 1
1. Perry-Keene J, Ferguson P, Samaratunga H, Nacey JN, Delahunt B. Total submission of pelvic lymphadenectomy tissues removed during radical prostatectomy for prostate cancer
2.
3.
4.
5.
6.
7.
increases lymph node yield and detection of micrometastasis. Histopathology 2014; 64; 399–404. Davis GL. Sensitivity of frozen section examination of pelvic lymph nodes for metastatic prostate carcinoma. Cancer 1995; 76; 661–668. Weing€ artner K, Ramaswamy A, Bittinger A, Gerharz EW, V€ oge D, Riedmiller H. Anatomical basis for pelvic lymphadenectomy in prostate cancer: results of an autopsy study and implications for the clinic. J. Urol. 1996; 156; 1969–1971. Boormans JL, Wildhagen MF, Bangma CH, Verhagen PC, van Leenders GJ. Histopathological characteristics of lymph node metastases predict cancer—specific survival in node-positive prostate cancer. BJU Int. 2008; 102; 1589–1593. Weaver DL. Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale. Mod. Pathol. 2010; 23(Suppl. 2); S26–S32. Murphy J, Pocard M, Jass JR, O’Sullivan GC, Lee G, Talbot IC. Number and size of lymph nodes recovered from Dukes B rectal cancer correlation with prognosis and histologic antitumor immune response. Dis. Colon Rectum 2007; 50; 1526–1534. Greco P, Andreola S, Magro G, Belli F, Gallino GF, Leo E. Potential pathological understaging of pT3 rectal cancers with less than 26 lymph nodes recovered from a prospective study based on a re-sampling of 50 rectal specimens. Virchows Arch. 2006; 449; 647–651.
Histopathology, 65, 722–730.
Effective maybe, but is it cost-effective? A reply DOI: 10.1111/his.12438 © 2014 John Wiley & Sons Ltd.
Sir: The letter from Varma and Griffiths in response to our study that investigated lymph node yield following processing of all tissues submitted from lymph node dissections in association with radical prostatectomy for prostate adenocarcinoma1 suggests that this should not be undertaken, on the basis of costeffectiveness. In the letter, the authors query how many additional blocks were required for the complete processing of lymphadenectomy tissues. No evidence-based guidelines for the sampling of these tissues currently exist. In our study, we identified palpable lymph nodes and then embedded the tissue completely. This necessitated the preparation of an additional three to five blocks per case. With a mean of 7.4 blocks per case, total embedding of lymphadenectomy tissue resulted in the detection of an additional 190% of lymph nodes.1 Varma and Griffiths make the point that a section taken through a lymph node may miss micrometastases. In support of this, they cite their unpublished study from 2007, which evaluated the utility of frozen sections of pelvic lymph nodes obtained during radical prostatectomy. They showed that frozen sections revealed metastatic tumour in 2% of cases, with a false-negative result being obtained in 3% of cases, following submission of the entire node for paraffin processing. Similar results were reported more than a decade earlier, when it was shown that frozen section assessment of lymph nodes for prostate cancer had a sensitivity of only 63.2%.2 These observations are not relevant to our study, as the majority of impalpable nodes are of small size, and sectioning therefore samples a substantial proportion of the node. There are no firm recommendations suggesting an optimum nodal harvest for patients undergoing radical prostatectomy for prostate cancer. In a postmortem study, it was shown that the mean number of lymph nodes removed during bilateral lymph node dissection was 22.7.3 This was similar to the mean number of 20.5 lymph nodes removed from patients undergoing radical prostatectomy. The authors noted that ~20 pelvic lymph nodes may serve as a guideline for sufficient standard pelvic lymph node dissection. It is of interest that, in support of these findings, total processing of our specimens resulted in the detection Histopathology, 65, 722–730.
729
of a mean number of 10.8 nodes per side. This indicates that total submission of pelvic lymphadenectomy tissue provides evidence of the adequacy of lymphadenectomy. In their letter, the authors query our ability to accurately identify and count the numbers of lymph nodes present. In reality, the technique that we employ makes this straightforward. First, as noted above, the impalpable nodes discovered following complete sampling are small, and are therefore well circumscribed and easily identified as discrete nodes. Second, we embed the lymphadenectomy specimen in serial blocks, and this makes it possible to match a partially sampled node in one block with the other portion of it in the adjacent block. The presence of metastases in lymph nodes is of prognostic significance for prostate cancer. In particular, it has been shown that both the maximum diameter of nodal metastases and the grade of nodal tumour are independent predictors of outcome on multivariate analysis.4 This underscores the importance of total submission of lymphadenectomy specimens. In our study, we identified additional metastatic prostatic cancer in 7.3% of cases, thus permitting more accurate assignment of tumour grade to lymph node metastases. In their concluding comments, Varma and Griffiths muse that it might be possible for additional lymph nodes to be be detected in other malignancies following submission of all tissues removed as part of a curative resection for cancer in a variety of organs. In this context, they particularly mention axillary lymph node dissections and colectomies. This latter argument is inappropriate, as the authors are confusing practicality and feasibility with cost-effectiveness. There are protocols in place to ensure optimum sampling of relevant nodes for patients with breast and rectal cancer, and these have been well validated.5–7 Such protocols remain to be established for prostate cancer; hence the purpose of our study. Varma and Griffiths conclude that processing of lymphadenectomy tissue is not cost-effective, and here their argument is on shaky ground. Although the data that we reported were from a formal study based on the material submitted to a solitary, specialized, private uropathology practice, in the three pathology units (one hospital and two private pathology practices) in which the authors work, all lymphadenectomy tissue are always routinely embedded, as this provides optimal prognostic information for the surgeon and also accurately informs subsequent treatment. The additional sections that are examined as a result of this are small and the costs
730
Correspondence
are trivial in relation to the total cost of the procedure and subsequent care. Joanna Perry-Keene1,2 Peter Ferguson3,4 Hemamali Samaratunga1 John N Nacey5 Brett Delahunt4 Aquesta Uropathology, 2Royal Brisbane Hospital, Brisbane, Qld, Australia, 3Wellington School of Medicine and Health Sciences, Malaghan Institute of Medical Research, University of Otago, 4Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, and 5 Department of Surgery, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand 1
1. Perry-Keene J, Ferguson P, Samaratunga H, Nacey JN, Delahunt B. Total submission of pelvic lymphadenectomy tissues removed during radical prostatectomy for prostate cancer
2.
3.
4.
5.
6.
7.
increases lymph node yield and detection of micrometastasis. Histopathology 2014; 64; 399–404. Davis GL. Sensitivity of frozen section examination of pelvic lymph nodes for metastatic prostate carcinoma. Cancer 1995; 76; 661–668. Weing€ artner K, Ramaswamy A, Bittinger A, Gerharz EW, V€ oge D, Riedmiller H. Anatomical basis for pelvic lymphadenectomy in prostate cancer: results of an autopsy study and implications for the clinic. J. Urol. 1996; 156; 1969–1971. Boormans JL, Wildhagen MF, Bangma CH, Verhagen PC, van Leenders GJ. Histopathological characteristics of lymph node metastases predict cancer—specific survival in node-positive prostate cancer. BJU Int. 2008; 102; 1589–1593. Weaver DL. Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale. Mod. Pathol. 2010; 23(Suppl. 2); S26–S32. Murphy J, Pocard M, Jass JR, O’Sullivan GC, Lee G, Talbot IC. Number and size of lymph nodes recovered from Dukes B rectal cancer correlation with prognosis and histologic antitumor immune response. Dis. Colon Rectum 2007; 50; 1526–1534. Greco P, Andreola S, Magro G, Belli F, Gallino GF, Leo E. Potential pathological understaging of pT3 rectal cancers with less than 26 lymph nodes recovered from a prospective study based on a re-sampling of 50 rectal specimens. Virchows Arch. 2006; 449; 647–651.
Histopathology, 65, 722–730.
