H. Furberg et al. / Urologic Oncology: Seminars and Original Investigations 33 (2015) 49–52
benefit calculation were computed from the PLCO cohort. The choice of threshold risk for eligibility was made by filtering on designs with positive net benefit, controlling for the size of the resulting screening trial. In contrast, the decision curve analysis of Mir et al. [3] which used the net benefit methodology as described in Vickers et al. [2], differed in the following ways. First, the computation of number screened in each hypothetical trial design was based on a comparison of threshold and predicted risk of HGBC incidence, while the expected events prevented in each hypothetical trial design was computed directly from a bladder cancer mortality end point. Rates of bladder cancer mortality required in this portion of the net benefit calculation were computed from the incidence of HGBC in the PLCO predicted from the model and 5-year bladder cancer survival by grade taken from the Statistical Epidemiologic Endpoints Registry given by Lynch and Platz [6]. The optimal hypothetical trial design was selected by filtering designs with positive net benefit, controlling for size of trial as well as the expected proportion of source cohort events selected for inclusion into the trial. Identifying individuals at high risk of HGBC, rather than ABC, results in a screening trial with a lower potential for overdiagnosis. The use of bladder cancer mortality in the net benefit computation, rather than HGBC incidence as a surrogate for mortality, together with the fact that the designs discussed could be considered feasible means that PI's need not resort to the use of a surrogate endpoint in the design of a bladder cancer screening trial. The optimum threshold risk of HGBC was a 5-year incidence of 2.82 per 1,000 personyears or roughly 56.4 per 100,000 person-years. The additional control over the expected proportion of events selected for inclusion provided an additional loss term on designs with too high of a risk threshold that would miss too great a proportion of events in the source cohort, which is an important consideration in choosing an optimal design. In summary, all 3 articles have the stated goal of determining a risk threshold for use in constructing eligibility criteria for some hypothetical future bladder cancer screening trial. The study by Krabbe et al. [1] used data from the PLCO and National Lung Screening Trial to fit a model for incidence of ABC but did no decision curve
Metastatic castrate-resistant prostate cancer To the Editor: The framework outlined by de Vere White and Lara in their article under “ news and topics,” Urologic Oncology: seminars and original investigations 32 2014; 380–382 describes a strategy of expanded multidisciplinary clinic activity and tumor board and teleconference interaction to address the explosion of scientific knowledge that has expanded the treatment options for men with castrate-resistant metastatic prostate cancer.
51
analysis and characterization based on their model the set of individuals with risk in excess of 2 cases per 1,000 personyears, a value taken from the literature on colon cancer screening. The studies by Vickers et al. [2] and Mir et al. [3] included a decision curve analysis, based on methodology presented Vickers et al. [2], but the study by Mir et al. [3] was the only one to model HGBC and consider hypothetical bladder cancer mortality trials, optimizing the net benefit while controlling for the size of the resulting screening trial as well as the expected proportion of events that had met the risk-based eligibility for trial. Grant Izmirlian, Ph.D.a Jon Paciorekb a National Cancer Institute, BG 9609 RM 5E130 MSC 9789, 9609 Medical Center Dr, Bethesda, MD 20892-9789 b Department of Engineering, Catholic University, 620 Michigan Ave., N.E., Washington DC 20064 Email address: [email protected] References [1] Krabbe L-M, Svatek RS, Shariat SF, Messing E, Lotan Y. Bladder cancer risk: use of the PLCO and NLST to identify a suitable screening cohort. Urol Oncol 2014:Available at: http://dx.doi.org/10.1016/j. urolonc.2014.06.009. [2] Vickers AJ, Bennette C, Kibel AS, Black A, Izmirlian G, Stephenson AJ, et al. Who should be included in a clinical trial of screening for bladder cancer? A decision analysis of data from the prostate, lung, colorectal and ovarian cancer screening trial. Cancer 2013;119:143–9. [3] Mir MC, Stephenson AJ, Grubb RL III, Black A, Kibel AS, Izmirlian G. Predicting risk of bladder cancer using clinical and demographic information from prostate, lung, colorectal, and ovarian cancer (PLCO) screening trial participants. Cancer Epidemiol Biomarkers Prev 2013; 22:2241–9. [4] Prorok PC, Andriole GL, Bresalier RS, Buys SS, Chia D, Crawford ED, et al. Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Control Clin Trials 2000;21:273S–309S. [5] Aberle DR, Berg CD, Black WC, Church TR, Fagerstrom RM, Galen B, et al. The national lung screening trial: overview and study design. Radiology 2011;258:243–53. [6] Lynch CF, Davilla JA, Platz CE. Cancer of urinary bladder. In: Ries LAG, Young JL Jr., Keel GE, et al. editors. SEER Survival Monograph: Cancer Survival Among Adult: U.S. Seer Program, 1998-2001, Patient and Tumor Characteristics. Bethesda, MD: National Cancer Institute, SEER Program; 2007.
However, in the near future, for most men in this disease state, is the complete multidisciplinary clinic model realistic and is the conference model sufficient? The M.D. clinic model outside a university faculty/ hospital setting where convenient, dedicated clinic space with common personnel, electronic medical records, and reimbursement plan, is a very difficult venture to implement and sustain. I am fortunate to reside in a progressive medical community where there is excellent cooperation among fellowship and specialty training urologists,
52
H. Furberg et al. / Urologic Oncology: Seminars and Original Investigations 33 (2015) 49–52
medical, and radiation oncologists with open-minded communication and regular reports and conferences. While all of these support systems provide an invaluable sounding board, information is relayed and decisions are finalized in the office where the individual physician makes face-to-face and hands on patient contact. A urologist embarking in this treatment space must be absolutely current. Even lapses of 6 months in education and interaction will diminish this currency. Moreover, the urologist cannot presume that referral to medical oncology provides a ready solution to the patient's care. A medical oncologist with a practice caring for patients with breast cancer, lung cancer, colon cancer is unable to be abreast of the developments in prostate cancer.
In either specialty, the immediate need calls for disease state–focused physician—a champion. These champions will be the near-term backbone delivering informed and current therapy for patients with castration-resistant metastatic prostate cancer. When these champions are identified and step forward, their unique needs must be recognized, encouraged, and supported. From their efforts, the de Vere White/Lara framework may eventually materialize.
Surgeons' preferences and practice patterns regarding intraoperative frozen section during partial nephrectomy
tumors in their retrospective study of renal cell carcinoma specimens. Do the authors have an opinion about surgeon preference in these patients? It was shown that the nephrectomy specimen after partial nephrectomy will contain tumor remnants in 6.9% to 15% of cases [4,5]. Radical nephrectomy can be done to these patients, especially in tumors with high malignant potential. However, it is not possible every time to find tumor in final pathology. By considering this situation, do the authors offer nephrectomy to these patients without IFS?
To the Editor: The authors conducted a study to evaluate the preferences and practice patterns of urologists regarding intraoperative frozen section (IFS) during partial nephrectomy. The risk of incomplete tumor removal is a major problem related to surgical outcomes of partial nephrectomy. It is unclear how to define the patient at risk for a positive surgical margin (PMS) and for disease recurrence after PMS and if the incidence of PMS is related to the surgical approach or technique [1]. To ensure negative margins, IFS) analysis of resected tumor is commonly done [2]. However, there are falsenegative or inconclusive results of IFS that do not correlate with the final pathology. Moreover, tumor-bed biopsies represent only a small fraction of the resection margin and generally deliver unreliable results [1]. The current article represents a different point of view of surgeons' and practice patterns regarding IFS during partial nephrectomy. The authors concluded that most surgeons still obtain IFS during partial nephrectomy despite low utility of frozen section. We believe IFS is time consuming during surgery because it does not give distinguishing knowledge about tumor remnants and we do not prefer taking routine frozen section. There is a great interest for performing partial nephrectomy to T1b stage tumors. However, partial nephrectomies may result in higher tumor recurrence rates because of PMSs or multifocal tumors [3]. Chen et al. [3] indicate that 4 mm may be optimal surgical margin for patients with T1b
Paul Schellhammer, M.D. Department of Urology, Eastern Virginia Medical School, Urology of Virginia, 225 Clearfield Road, Virginia Bench, Virginia 23462
Yasin Ceylan, M.D. Bülent Günlüsoy, M.D. Department of Urology, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
References [1] Marszalek M, Carini M, Chlosta P, Jeschke K, Kirkali Z, Knüchel R. Positive surgical margins after nephron-sparing surgery. Eur Urol 2012;61:757–63. [2] Sidana A, Donovan JF, Gaitonde K. Surgeons' preferences and practice patterns regarding intraoperative frozen section during partial nephrectomy. Urol Oncol 2014;32:864–8. [3] Chen XS, Zhang ZT, Du J, Bi XC, Sun G, Yao X. Optimal surgical margin in nephron-sparing surgery for T1b renal cell carcinoma. Urology 2012;79:836–9. [4] Raz O, Mendlovic S, Shilo Y, et al. Positive surgical margins with renal cell carcinoma have a limited influence on long-term oncological outcomes of nephron-sparing surgery. Urology 2010;75:277–80. [5] Sundram V, Figenshau RS, Roytman TM, et al. Positive margin during partial neprectomy: does cancer remain in the renal remnant? Urology 2011;77:1400–3.
benefit calculation were computed from the PLCO cohort. The choice of threshold risk for eligibility was made by filtering on designs with positive net benefit, controlling for the size of the resulting screening trial. In contrast, the decision curve analysis of Mir et al. [3] which used the net benefit methodology as described in Vickers et al. [2], differed in the following ways. First, the computation of number screened in each hypothetical trial design was based on a comparison of threshold and predicted risk of HGBC incidence, while the expected events prevented in each hypothetical trial design was computed directly from a bladder cancer mortality end point. Rates of bladder cancer mortality required in this portion of the net benefit calculation were computed from the incidence of HGBC in the PLCO predicted from the model and 5-year bladder cancer survival by grade taken from the Statistical Epidemiologic Endpoints Registry given by Lynch and Platz [6]. The optimal hypothetical trial design was selected by filtering designs with positive net benefit, controlling for size of trial as well as the expected proportion of source cohort events selected for inclusion into the trial. Identifying individuals at high risk of HGBC, rather than ABC, results in a screening trial with a lower potential for overdiagnosis. The use of bladder cancer mortality in the net benefit computation, rather than HGBC incidence as a surrogate for mortality, together with the fact that the designs discussed could be considered feasible means that PI's need not resort to the use of a surrogate endpoint in the design of a bladder cancer screening trial. The optimum threshold risk of HGBC was a 5-year incidence of 2.82 per 1,000 personyears or roughly 56.4 per 100,000 person-years. The additional control over the expected proportion of events selected for inclusion provided an additional loss term on designs with too high of a risk threshold that would miss too great a proportion of events in the source cohort, which is an important consideration in choosing an optimal design. In summary, all 3 articles have the stated goal of determining a risk threshold for use in constructing eligibility criteria for some hypothetical future bladder cancer screening trial. The study by Krabbe et al. [1] used data from the PLCO and National Lung Screening Trial to fit a model for incidence of ABC but did no decision curve
Metastatic castrate-resistant prostate cancer To the Editor: The framework outlined by de Vere White and Lara in their article under “ news and topics,” Urologic Oncology: seminars and original investigations 32 2014; 380–382 describes a strategy of expanded multidisciplinary clinic activity and tumor board and teleconference interaction to address the explosion of scientific knowledge that has expanded the treatment options for men with castrate-resistant metastatic prostate cancer.
51
analysis and characterization based on their model the set of individuals with risk in excess of 2 cases per 1,000 personyears, a value taken from the literature on colon cancer screening. The studies by Vickers et al. [2] and Mir et al. [3] included a decision curve analysis, based on methodology presented Vickers et al. [2], but the study by Mir et al. [3] was the only one to model HGBC and consider hypothetical bladder cancer mortality trials, optimizing the net benefit while controlling for the size of the resulting screening trial as well as the expected proportion of events that had met the risk-based eligibility for trial. Grant Izmirlian, Ph.D.a Jon Paciorekb a National Cancer Institute, BG 9609 RM 5E130 MSC 9789, 9609 Medical Center Dr, Bethesda, MD 20892-9789 b Department of Engineering, Catholic University, 620 Michigan Ave., N.E., Washington DC 20064 Email address: [email protected] References [1] Krabbe L-M, Svatek RS, Shariat SF, Messing E, Lotan Y. Bladder cancer risk: use of the PLCO and NLST to identify a suitable screening cohort. Urol Oncol 2014:Available at: http://dx.doi.org/10.1016/j. urolonc.2014.06.009. [2] Vickers AJ, Bennette C, Kibel AS, Black A, Izmirlian G, Stephenson AJ, et al. Who should be included in a clinical trial of screening for bladder cancer? A decision analysis of data from the prostate, lung, colorectal and ovarian cancer screening trial. Cancer 2013;119:143–9. [3] Mir MC, Stephenson AJ, Grubb RL III, Black A, Kibel AS, Izmirlian G. Predicting risk of bladder cancer using clinical and demographic information from prostate, lung, colorectal, and ovarian cancer (PLCO) screening trial participants. Cancer Epidemiol Biomarkers Prev 2013; 22:2241–9. [4] Prorok PC, Andriole GL, Bresalier RS, Buys SS, Chia D, Crawford ED, et al. Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Control Clin Trials 2000;21:273S–309S. [5] Aberle DR, Berg CD, Black WC, Church TR, Fagerstrom RM, Galen B, et al. The national lung screening trial: overview and study design. Radiology 2011;258:243–53. [6] Lynch CF, Davilla JA, Platz CE. Cancer of urinary bladder. In: Ries LAG, Young JL Jr., Keel GE, et al. editors. SEER Survival Monograph: Cancer Survival Among Adult: U.S. Seer Program, 1998-2001, Patient and Tumor Characteristics. Bethesda, MD: National Cancer Institute, SEER Program; 2007.
However, in the near future, for most men in this disease state, is the complete multidisciplinary clinic model realistic and is the conference model sufficient? The M.D. clinic model outside a university faculty/ hospital setting where convenient, dedicated clinic space with common personnel, electronic medical records, and reimbursement plan, is a very difficult venture to implement and sustain. I am fortunate to reside in a progressive medical community where there is excellent cooperation among fellowship and specialty training urologists,
52
H. Furberg et al. / Urologic Oncology: Seminars and Original Investigations 33 (2015) 49–52
medical, and radiation oncologists with open-minded communication and regular reports and conferences. While all of these support systems provide an invaluable sounding board, information is relayed and decisions are finalized in the office where the individual physician makes face-to-face and hands on patient contact. A urologist embarking in this treatment space must be absolutely current. Even lapses of 6 months in education and interaction will diminish this currency. Moreover, the urologist cannot presume that referral to medical oncology provides a ready solution to the patient's care. A medical oncologist with a practice caring for patients with breast cancer, lung cancer, colon cancer is unable to be abreast of the developments in prostate cancer.
In either specialty, the immediate need calls for disease state–focused physician—a champion. These champions will be the near-term backbone delivering informed and current therapy for patients with castration-resistant metastatic prostate cancer. When these champions are identified and step forward, their unique needs must be recognized, encouraged, and supported. From their efforts, the de Vere White/Lara framework may eventually materialize.
Surgeons' preferences and practice patterns regarding intraoperative frozen section during partial nephrectomy
tumors in their retrospective study of renal cell carcinoma specimens. Do the authors have an opinion about surgeon preference in these patients? It was shown that the nephrectomy specimen after partial nephrectomy will contain tumor remnants in 6.9% to 15% of cases [4,5]. Radical nephrectomy can be done to these patients, especially in tumors with high malignant potential. However, it is not possible every time to find tumor in final pathology. By considering this situation, do the authors offer nephrectomy to these patients without IFS?
To the Editor: The authors conducted a study to evaluate the preferences and practice patterns of urologists regarding intraoperative frozen section (IFS) during partial nephrectomy. The risk of incomplete tumor removal is a major problem related to surgical outcomes of partial nephrectomy. It is unclear how to define the patient at risk for a positive surgical margin (PMS) and for disease recurrence after PMS and if the incidence of PMS is related to the surgical approach or technique [1]. To ensure negative margins, IFS) analysis of resected tumor is commonly done [2]. However, there are falsenegative or inconclusive results of IFS that do not correlate with the final pathology. Moreover, tumor-bed biopsies represent only a small fraction of the resection margin and generally deliver unreliable results [1]. The current article represents a different point of view of surgeons' and practice patterns regarding IFS during partial nephrectomy. The authors concluded that most surgeons still obtain IFS during partial nephrectomy despite low utility of frozen section. We believe IFS is time consuming during surgery because it does not give distinguishing knowledge about tumor remnants and we do not prefer taking routine frozen section. There is a great interest for performing partial nephrectomy to T1b stage tumors. However, partial nephrectomies may result in higher tumor recurrence rates because of PMSs or multifocal tumors [3]. Chen et al. [3] indicate that 4 mm may be optimal surgical margin for patients with T1b
Paul Schellhammer, M.D. Department of Urology, Eastern Virginia Medical School, Urology of Virginia, 225 Clearfield Road, Virginia Bench, Virginia 23462
Yasin Ceylan, M.D. Bülent Günlüsoy, M.D. Department of Urology, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
References [1] Marszalek M, Carini M, Chlosta P, Jeschke K, Kirkali Z, Knüchel R. Positive surgical margins after nephron-sparing surgery. Eur Urol 2012;61:757–63. [2] Sidana A, Donovan JF, Gaitonde K. Surgeons' preferences and practice patterns regarding intraoperative frozen section during partial nephrectomy. Urol Oncol 2014;32:864–8. [3] Chen XS, Zhang ZT, Du J, Bi XC, Sun G, Yao X. Optimal surgical margin in nephron-sparing surgery for T1b renal cell carcinoma. Urology 2012;79:836–9. [4] Raz O, Mendlovic S, Shilo Y, et al. Positive surgical margins with renal cell carcinoma have a limited influence on long-term oncological outcomes of nephron-sparing surgery. Urology 2010;75:277–80. [5] Sundram V, Figenshau RS, Roytman TM, et al. Positive margin during partial neprectomy: does cancer remain in the renal remnant? Urology 2011;77:1400–3.
