EUROPEAN UROLOGY 67 (2015) 458–459
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. 451–457 of this issue
Positive Surgical Margins: Race or Surgeon? Alexandre R. Zlotta a,b,c,*, Cynthia Kuk a,c a
Department of Surgery, Urology, Mount Sinai Hospital, Toronto, Canada;
b
University of Toronto, Toronto, Canada; c Department of Surgical Oncology,
Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
The present study by Jalloh et al. published in this month’s issue of European Urology aimed to investigate the influence of racial variations on pathologic outcome after radical prostatectomy (RP) for low-risk prostate cancer (PCa) patients. The positive surgical margin (PSM) rate was significantly higher in the African American group (31%) than in the Caucasian group (21%) [1]. This well-known and respected group of authors concluded, after adjusting for appropriate confounders, that the rate of upstaging and upgrading is not influenced by race. They found that the rate of PSMs was significantly higher in African American men. The exact reasons are still unclear, but this observation is certainly hypothesis generating. Given that a disproportionate number of African American men are diagnosed with PCa each year and are likely to die from the disease, the authors should be commended for having addressed this important question. Their patient cohort had major limitations that included having only a very small percentage of African American men available for analysis, 6.5% of the entire cohort [1]. In addition, race was associated with PSMs among men who were treated at community-based clinics but not in the subset treated at academic centers. Of note, PSM rates were also strikingly lower at academic sites (15%) versus community-based sites (24%) ( p < 0.01), and the authors were unable to adjust the analyses by surgeon, given the large number of participating operators. Several other reasons for a PSM can be proposed, like extensive nervepreservation attempts, wide differences in surgeon experience, and surgical technique. Using retrospectively gathered margins data from 14 institutions worldwide on 9778 open RPs, positive
margins were observed in 22.8% [2]. Interestingly, 62% of these cases were pathologically pT2, whereas in the paper by Jalloh et al. [1], whether in African American or Caucasian men, 87% of PCa was pT2. Consequently, because PSMs are often viewed as a surrogate for the quality of surgery in pathologically organ-confined disease, a PSM rate of 31% seems higher than what has been consistently published by high-volume centers, especially in low-risk patients [3]. The likelihood of PSMs seems to be strongly influenced by the surgeon’s experience, regardless of the surgical approach [4]. It is unclear whether focal margins carry a major prognostic and predictive value, especially for patients with low-risk PCa, but unifocality versus multifocality was not available in the present paper, and that is another limitation [1]. PSM is considered a ‘‘bad’’ outcome after RP and is associated with an increased risk of prostate-specific antigen (PSA) recurrence, but its association with longterm end points such as PCa metastases or survival remains unclear [4,5]. Analyzing data from 1712 patients from a high-volume center with pT2–4 N0 PCa and undetectable PSA after RP, 10-yr estimates for biochemical recurrencefree survival were 82% for patients with negative surgical margins, 72% for patients with a solitary PSM, and 59% for patients with multiple PSMs ( p < 0.0001) [5]. Positive margins did not convey a significantly worse outcome for metastatic disease or PCa-specific survival ( p = 0.988 for overall survival). Yet PSM is likely a cause of patient anxiety and is associated with an increased administration rate of postoperative radiotherapy and related costs and complications. Although PSMs in PCa are considered an adverse
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2014.03.026. * Corresponding author. Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and Princess Margaret Cancer Centre, University Health Network, 60 Murray Street, 6th Floor, Box 19, Toronto, Ontario, M5T 3L9, Canada. Tel. +1 416 586 4800 ext 3910; Fax: +1 416 586 4776. E-mail address: [email protected] (A.R. Zlotta). http://dx.doi.org/10.1016/j.eururo.2014.05.036 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY 67 (2015) 458–459
oncologic outcome, their long-term impact on survival is highly variable and is largely influenced by other risk modifiers. As much as we all try to minimize this aspect and aim at achieving some uniformity of outcomes across techniques and practitioners, RP is a procedure heavily influenced by the surgeon [6]. Especially in low-risk PCa and pathologically confined disease, nerve sparing is performed to preserve the patient’s potency without compromising surgical extent and the chance of curing the patient from his cancer by leaving tumor behind. The hands that perform RP can have a significant impact on outcomes, and higher-volume surgeons tend to have better oncologic and functional outcomes [6]. Surgeons should strive for low PSM rates. Constant review of their individual margins may ultimately improve outcomes. Cancer Care Ontario, for example, recently undertook an audit of pathology reports to determine the province wide PSM rate for pathological stage T2 (pT2) PCa and to assess the overall and regional PSM rates based on surgical volume to understand gaps in quality of care prior to undertaking quality improvement initiatives [7]. This initiative led to improved outcomes within only a few years. Finally, interobserver variability, even between expert urologic pathologists, has been reported for surgical margin status in RP specimens, and this aspect should not be overlooked [8]. In the present study by Jalloh et al. [1], despite the best attempts at minimizing confounders, it looks as if the increased PCa margin rate was likely influenced by the surgeon and the center where surgery was carried out rather than the ethnic background. Despite a lower number of prostate biopsies in African American men, no difference in upstaging or upgrading of African American and Caucasian men was observed from clinical to pathological assessment [1]. This could indicate that in low-risk disease, PCa biology might be relatively similar across ethnic groups, and differences in PCa mortality seen between African American and Caucasian men might be limited to more aggressive forms of the disease. Even after extensive studies of the topic and especially with respect to risk factors [9], scientists do not fully
459
understand why PCa incidence and death rates are higher within the African American population, and more research is definitely warranted. Starting by trying to improve outcomes with surgeons paying close attention and monitoring their own PSM rates in pT2 disease is one way to go. Conflicts of interest: The authors have nothing to disclose.
References [1] Jalloh M, Myers F, Cowan JE, Carroll PR, Cooperberg MR. Racial variation in prostate cancer upgrading and upstaging among men with low risk clinical characteristics. Eur Urol 2015;67:451–7. [2] Sooriakumaran P, Srivastava A, Shariat SF, et al. A multinational, multi-institutional study comparing positive surgical margin rates among 22 393 open, laparoscopic, and robot-assisted radical prostatectomy patients. Eur Urol 2014;66:450–6. [3] Satkunasivam R, Kulkarni GS, Zlotta AR, et al. Pathological, oncologic and functional outcomes of radical prostatectomy following active surveillance. J Urol 2013;190:91–5. [4] Yossepowitch O, Briganti A, Eastham JA, et al. Positive surgical margins after radical prostatectomy: a systematic review and contemporary update. Eur Urol 2014;65:303–13. [5] Mauermann J, Fradet V, Lacombe L, et al. The impact of solitary and multiple positive surgical margins on hard clinical end points in 1712 adjuvant treatment-naive pT2-4 N0 radical prostatectomy patients. Eur Urol 2013;64:19–25. [6] Vickers A, Savage C, Bianco F, et al. Cancer control and functional outcomes after radical prostatectomy as markers of surgical quality: analysis of heterogeneity between surgeons at a single cancer center. Eur Urol 2011;59:317–22. [7] Lawrentschuk N, Evans A, Srigley J, et al. Surgical margin status among men with organ-confined (pT2) prostate cancer: a population-based study. Can Urol Assoc J 2011;5:161–6. [8] Evans AJ, Henry PC, Van der Kwast TH, et al. Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. Am J Surg Pathol 2008;32:1503–12. [9] Haiman CA, Chen GK, Blot WJ, et al. Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21. Nat Genet 2011;43:570–3.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. 451–457 of this issue
Positive Surgical Margins: Race or Surgeon? Alexandre R. Zlotta a,b,c,*, Cynthia Kuk a,c a
Department of Surgery, Urology, Mount Sinai Hospital, Toronto, Canada;
b
University of Toronto, Toronto, Canada; c Department of Surgical Oncology,
Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
The present study by Jalloh et al. published in this month’s issue of European Urology aimed to investigate the influence of racial variations on pathologic outcome after radical prostatectomy (RP) for low-risk prostate cancer (PCa) patients. The positive surgical margin (PSM) rate was significantly higher in the African American group (31%) than in the Caucasian group (21%) [1]. This well-known and respected group of authors concluded, after adjusting for appropriate confounders, that the rate of upstaging and upgrading is not influenced by race. They found that the rate of PSMs was significantly higher in African American men. The exact reasons are still unclear, but this observation is certainly hypothesis generating. Given that a disproportionate number of African American men are diagnosed with PCa each year and are likely to die from the disease, the authors should be commended for having addressed this important question. Their patient cohort had major limitations that included having only a very small percentage of African American men available for analysis, 6.5% of the entire cohort [1]. In addition, race was associated with PSMs among men who were treated at community-based clinics but not in the subset treated at academic centers. Of note, PSM rates were also strikingly lower at academic sites (15%) versus community-based sites (24%) ( p < 0.01), and the authors were unable to adjust the analyses by surgeon, given the large number of participating operators. Several other reasons for a PSM can be proposed, like extensive nervepreservation attempts, wide differences in surgeon experience, and surgical technique. Using retrospectively gathered margins data from 14 institutions worldwide on 9778 open RPs, positive
margins were observed in 22.8% [2]. Interestingly, 62% of these cases were pathologically pT2, whereas in the paper by Jalloh et al. [1], whether in African American or Caucasian men, 87% of PCa was pT2. Consequently, because PSMs are often viewed as a surrogate for the quality of surgery in pathologically organ-confined disease, a PSM rate of 31% seems higher than what has been consistently published by high-volume centers, especially in low-risk patients [3]. The likelihood of PSMs seems to be strongly influenced by the surgeon’s experience, regardless of the surgical approach [4]. It is unclear whether focal margins carry a major prognostic and predictive value, especially for patients with low-risk PCa, but unifocality versus multifocality was not available in the present paper, and that is another limitation [1]. PSM is considered a ‘‘bad’’ outcome after RP and is associated with an increased risk of prostate-specific antigen (PSA) recurrence, but its association with longterm end points such as PCa metastases or survival remains unclear [4,5]. Analyzing data from 1712 patients from a high-volume center with pT2–4 N0 PCa and undetectable PSA after RP, 10-yr estimates for biochemical recurrencefree survival were 82% for patients with negative surgical margins, 72% for patients with a solitary PSM, and 59% for patients with multiple PSMs ( p < 0.0001) [5]. Positive margins did not convey a significantly worse outcome for metastatic disease or PCa-specific survival ( p = 0.988 for overall survival). Yet PSM is likely a cause of patient anxiety and is associated with an increased administration rate of postoperative radiotherapy and related costs and complications. Although PSMs in PCa are considered an adverse
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2014.03.026. * Corresponding author. Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and Princess Margaret Cancer Centre, University Health Network, 60 Murray Street, 6th Floor, Box 19, Toronto, Ontario, M5T 3L9, Canada. Tel. +1 416 586 4800 ext 3910; Fax: +1 416 586 4776. E-mail address: [email protected] (A.R. Zlotta). http://dx.doi.org/10.1016/j.eururo.2014.05.036 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY 67 (2015) 458–459
oncologic outcome, their long-term impact on survival is highly variable and is largely influenced by other risk modifiers. As much as we all try to minimize this aspect and aim at achieving some uniformity of outcomes across techniques and practitioners, RP is a procedure heavily influenced by the surgeon [6]. Especially in low-risk PCa and pathologically confined disease, nerve sparing is performed to preserve the patient’s potency without compromising surgical extent and the chance of curing the patient from his cancer by leaving tumor behind. The hands that perform RP can have a significant impact on outcomes, and higher-volume surgeons tend to have better oncologic and functional outcomes [6]. Surgeons should strive for low PSM rates. Constant review of their individual margins may ultimately improve outcomes. Cancer Care Ontario, for example, recently undertook an audit of pathology reports to determine the province wide PSM rate for pathological stage T2 (pT2) PCa and to assess the overall and regional PSM rates based on surgical volume to understand gaps in quality of care prior to undertaking quality improvement initiatives [7]. This initiative led to improved outcomes within only a few years. Finally, interobserver variability, even between expert urologic pathologists, has been reported for surgical margin status in RP specimens, and this aspect should not be overlooked [8]. In the present study by Jalloh et al. [1], despite the best attempts at minimizing confounders, it looks as if the increased PCa margin rate was likely influenced by the surgeon and the center where surgery was carried out rather than the ethnic background. Despite a lower number of prostate biopsies in African American men, no difference in upstaging or upgrading of African American and Caucasian men was observed from clinical to pathological assessment [1]. This could indicate that in low-risk disease, PCa biology might be relatively similar across ethnic groups, and differences in PCa mortality seen between African American and Caucasian men might be limited to more aggressive forms of the disease. Even after extensive studies of the topic and especially with respect to risk factors [9], scientists do not fully
459
understand why PCa incidence and death rates are higher within the African American population, and more research is definitely warranted. Starting by trying to improve outcomes with surgeons paying close attention and monitoring their own PSM rates in pT2 disease is one way to go. Conflicts of interest: The authors have nothing to disclose.
References [1] Jalloh M, Myers F, Cowan JE, Carroll PR, Cooperberg MR. Racial variation in prostate cancer upgrading and upstaging among men with low risk clinical characteristics. Eur Urol 2015;67:451–7. [2] Sooriakumaran P, Srivastava A, Shariat SF, et al. A multinational, multi-institutional study comparing positive surgical margin rates among 22 393 open, laparoscopic, and robot-assisted radical prostatectomy patients. Eur Urol 2014;66:450–6. [3] Satkunasivam R, Kulkarni GS, Zlotta AR, et al. Pathological, oncologic and functional outcomes of radical prostatectomy following active surveillance. J Urol 2013;190:91–5. [4] Yossepowitch O, Briganti A, Eastham JA, et al. Positive surgical margins after radical prostatectomy: a systematic review and contemporary update. Eur Urol 2014;65:303–13. [5] Mauermann J, Fradet V, Lacombe L, et al. The impact of solitary and multiple positive surgical margins on hard clinical end points in 1712 adjuvant treatment-naive pT2-4 N0 radical prostatectomy patients. Eur Urol 2013;64:19–25. [6] Vickers A, Savage C, Bianco F, et al. Cancer control and functional outcomes after radical prostatectomy as markers of surgical quality: analysis of heterogeneity between surgeons at a single cancer center. Eur Urol 2011;59:317–22. [7] Lawrentschuk N, Evans A, Srigley J, et al. Surgical margin status among men with organ-confined (pT2) prostate cancer: a population-based study. Can Urol Assoc J 2011;5:161–6. [8] Evans AJ, Henry PC, Van der Kwast TH, et al. Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. Am J Surg Pathol 2008;32:1503–12. [9] Haiman CA, Chen GK, Blot WJ, et al. Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21. Nat Genet 2011;43:570–3.
![[Positive surgical margins after radical prostatectomy].](/assets/img/hold.png)
