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Incidence of initial local therapy among men with lower-risk prostate cancer in the United States
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B. Konety / Urologic Oncology: Seminars and Original Investigations 25 (2007) 87–95
genitourinary group within the American College of Surgeons Oncology Group, which is the only cooperative group focusing on trials in surgical oncology. doi:10.1016/j.urolonc.2006.11.003 Badrinath Konety, M.D., M.B.A. Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of < or ⴝ10 ng/mL and biopsy Gleason score of < or ⴝ6, and their influence on PSA progression-free survival after radical prostatectomy. Weckermann D, Goppelt M, Dorn R, Wawroschek F, Harzmann R, Department of Urology, Klinikum Augsburg, Augsburg, Germany. BJU Int 2006;97:1173– 8 Objective: To investigate how many men with low-risk prostate cancer had positive lymph nodes detected by radio-guided surgery and whether they had a higher biochemical relapse rate after radical prostatectomy, because in such patients most urologists dispense with operative lymph node staging, as nomograms indicate only a low percentage of lymph node metastases. Patients and Methods: The study included 474 men with a prostate-specific antigen (PSA) level of ⬍ or ⫽ 10 ng/mL, biopsy Gleason score of ⬍ or ⫽ 6 and positive biopsies in one (group 1, 315 men) or both lobes (group 2, 159 men); follow-up data were available in 357 men. Men with adjuvant radiation or hormone therapy before the occurrence of biochemical relapse were excluded. Results: Positive lymph nodes were detected in 17 men in group 1, and in 18 in group 2. In more than half of the patients (19/35) these nodes were found outside the region of standard lymphadenectomy. Men with node-positive disease had a higher biochemical relapse rate (P ⬍ 0.001). When the tumour was organ-confined and well differentiated in node-positive disease (Gleason score ⬍ or ⫽ 6) the biochemical relapse rate was lower than in men with higher tumour stage and grade. Conclusions: When dissecting pelvic lymph nodes, extended or sentinel lymphadenectomy should be preferred. Removing the diseased nodes could improve the PSA progression-free survival, especially in well differentiated organ-confined disease.
Commentary This study used intraoperative scintigraphic imaging to identify potentially positive lymph nodes in men undergoing radical prostatectomy for low-risk prostate cancer. By using more meticulous pathologic examination, the authors were able to identify lymph node metastases in 7% of these patients, which is marginally higher than what would have been predicted using published nomograms. The largest subset of the patients (34.5%) had positive nodes along the internal iliac artery. These data highlight the need to perform a large field node dissection in prostate cancer and the potential use of intraoperative imaging in identifying those patients with node positive disease. doi:10.1016/j.urolonc.2006.11.004 Badrinath Konety, M.D., M.B.A. Incidence of initial local therapy among men with lower-risk prostate cancer in the United States. Miller DC, Gruber SB, Hollenbeck BK, Montie JE, Wei JT, Department of Urology, University of Michigan, Ann Arbor, MI. J Natl Cancer Inst 2006;98:1134 – 41 Background: The frequently indolent nature of early-stage prostate cancer in older men and in men with low- or moderate-grade tumors and the demonstration that the survival benefits of radical prostatectomy are primarily among men younger than 65 years have led to concerns about prostate cancer overtreatment. Methods: Using data from 13 Surveillance, Epidemiology, and End Results registries, we performed a retrospective cohort study of 71,602 men who were diagnosed with localized or regional prostate cancer between 2000 and 2002. We quantified the incidence of initial curative therapy (i.e., surgery or radiation therapy) among men with lower-risk cancers as defined by their limited likelihood of either dying from expectantly managed prostate cancer or achieving a survival benefit from local therapy. Stratified analyses and multinomial logistic regression models were used to quantify the absolute and relative rates of curative therapy among men in various age-grade strata. All statistical tests were two-sided. Results: We identified 24,405 men with lower-risk prostate cancers and complete data for the first course of treatment. Initial curative therapy was undertaken in 13,537 of these men (55%); 81% of treated men received radiation therapy. The likelihood of curative therapy, relative to expectant management, varied statistically significantly among lower-risk age-grade strata (all P ⬍ .05). Assuming that initial expectant management is appropriate for all lower-risk cancers, 2564 men (10%) in this population-based sample were overtreated with radical prostatectomy and 10,973 (45%) with radiation therapy. Conclusions: These data quantify a target population for whom greater use of expectant approaches may reduce overtreatment and improve the quality of localized prostate cancer care.
Commentary These authors conducted a retrospective analysis of treatment patterns for lower risk prostate cancer using the Surveillance, Epidemiology, and End Results data set, and compared trends over 2 time periods, 10 years apart. The definition of lower risk disease was basically
K. Anderson / Urologic Oncology: Seminars and Original Investigations 25 (2007) 87–95
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based on grade of tumor and patient age, which adopts a more patient-centered approach, rather than a disease-focused approach of most conventional risk stratification schema. It is interesting to note that high rates of curative therapy, mainly radiation therapy, were observed in patients with low-risk disease. Although radical prostatectomy was age sensitive, radiation therapy use did not change with age, even beyond 75 years when treatment value is very questionable. This result may be fostered by an impression that these men better tolerated radiation therapy. However, that still does not justify overtreatment. Most interestingly, the rate of expectant management/androgen deprivation therapy for men with poorly differentiated cancer was higher than that for moderately differentiated tumors. This relative underutilization of curative treatment is hard to explain. It is possible that this may be a gross overestimation, given that many men may have received neoadjuvant hormonal therapy, followed by radiation, which is not captured in the Surveillance, Epidemiology, and End Results database. Although it is to be acknowledged that single modality curative therapy is not uniformly effective in men with high Gleason tumors, the efficacy is not so low as to justify switching to expectant treatment or primary androgen deprivation therapy. doi:10.1016/j.urolonc.2006.11.005 Badrinath Konety, M.D., M.B.A.
LABORATORY RESEARCH Comparison of holding strength of suture anchors for hepatic and renal parenchyma. Ames CD, Perrone JM, Frisella AJ, Morrissey K, Landman J, Division of Urology, Washington University School of Medicine, St. Louis, MO. J Endourol 2005;19:1221–5 Background and Purpose: Various laparoscopic devices have been described for suture anchoring during solid organ parenchymal closure. Application of these devices expedites the closure of parenchymal defects and minimizes ischemia time. We compared different technologies as suture anchors for parenchymal closure. Materials and Methods: A tensometer was used to determine the amount of tension necessary to dislodge each of five different clips from Vicryl suture alone or against two different substrates (fresh pig kidney and liver) with and without an intervening pledget. The clips investigated were the Lapra-Ty (Ethicon), Endoclip II (US Surgical), small Horizon Ligating Clips (Weck), Hem-o-lok Medium Polymer Clips (Weck), and a novel Suture-clip (Applied Medical). ANOVA and two-sided Fisher’s exact test provided statistical analysis. Results: The force required to dislodge the Lapra-Ty clip from bare suture for both 0 and 1 Vicryl (7.0 N) was approximately fourfold the force required to dislodge the Endoclips or the 5-mm or 10-mm Hem-o-lok clips (p⬍0.01). When clips were applied to suture running through renal or liver parenchyma, the novel Suture-clip required the greatest tension to dislodge (P⬍0.01), followed by the Horizon and Lapra-Ty clips. There were no statistically significant differences in the tension required to dislodge a given clip from the two parenchymal substrates or in the presence or absence of a pledget. Conclusions: In our experimental model, the Suture-clip, Lapra-Ty, and Horizon clips required significantly greater tension to dislodge than the Hem-o-lok and Endoclip clips. The addition of a pledget did not improve tension resistance. Commentary Although laparoscopic knot tying is a skill that can be learned through repetition in a dry lab, the use of this technique for laparoscopic partial nephrectomy can make for a challenging and often rather frustrating time in the operating room. Laparoscopic approximation of renal tissue through tensioning of sutures over bolsters is difficult enough but then to tie a knot while maintaining adequate tension may require an assistant to “hold” the knot while the second throw is prepared. To overcome this problem, a number of suture anchoring devices have been developed to obviate the need for knot tying. In this article, Ames et al. evaluated suture anchoring devices and found that of the commercially available anchors, both the Horizon Ligating Clips and the Lapra-Ty held suture well enough to resist suture tensioning forces great enough to cause renal parenchymal tearing. Although these anchors were not compared against a traditional surgical knot, any anchor that can hold a suture against tension sufficient to tear through the renal parenchyma is likely adequate for use during laparoscopic partial nephrectomy. Interestingly, there was an equal frequency of parenchymal tearing whether or not a Surgicel pledget was inserted between the anchor and the parenchyma. Although the use of these devices has been previously reported in small clinical series, this report should help alleviate any doubt about the effectiveness of these devices for use during partial nephrectomy. Despite the proliferation of hemostatic agents and energy based coagulation devices (ultrasonic shears, radiofrequency based coagulation, etc.), there are currently no well-proven alternatives to sutured repairs (generally with bolsters) following large and deep partial nephrectomy resections. The Horizon Ligating Clip or Lapra-Ty make repair after this type of laparoscopic partial nephrectomy significantly more rapid than can be achieved with knot tying. doi:10.1016/j.urolonc.2006.08.023 Kyle Anderson, M.D. Acute integrity of closure for partial nephrectomy: Comparison of 7 agents in a hypertensive porcine model. Johnston WK III, Kelel KM, Hollenbeck BK, Daignault S, Wolf JS Jr, Department of Urology, University of Michigan and Veterans Administration Medical Center, Ann Arbor, MI. J Urol 2006;175:2307-11 Purpose: We assessed the acute effectiveness of closure after partial nephrectomy of 7 techniques in a large hypertensive porcine model using shallow and deep resections to approximate clinical situations.
B. Konety / Urologic Oncology: Seminars and Original Investigations 25 (2007) 87–95
genitourinary group within the American College of Surgeons Oncology Group, which is the only cooperative group focusing on trials in surgical oncology. doi:10.1016/j.urolonc.2006.11.003 Badrinath Konety, M.D., M.B.A. Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of < or ⴝ10 ng/mL and biopsy Gleason score of < or ⴝ6, and their influence on PSA progression-free survival after radical prostatectomy. Weckermann D, Goppelt M, Dorn R, Wawroschek F, Harzmann R, Department of Urology, Klinikum Augsburg, Augsburg, Germany. BJU Int 2006;97:1173– 8 Objective: To investigate how many men with low-risk prostate cancer had positive lymph nodes detected by radio-guided surgery and whether they had a higher biochemical relapse rate after radical prostatectomy, because in such patients most urologists dispense with operative lymph node staging, as nomograms indicate only a low percentage of lymph node metastases. Patients and Methods: The study included 474 men with a prostate-specific antigen (PSA) level of ⬍ or ⫽ 10 ng/mL, biopsy Gleason score of ⬍ or ⫽ 6 and positive biopsies in one (group 1, 315 men) or both lobes (group 2, 159 men); follow-up data were available in 357 men. Men with adjuvant radiation or hormone therapy before the occurrence of biochemical relapse were excluded. Results: Positive lymph nodes were detected in 17 men in group 1, and in 18 in group 2. In more than half of the patients (19/35) these nodes were found outside the region of standard lymphadenectomy. Men with node-positive disease had a higher biochemical relapse rate (P ⬍ 0.001). When the tumour was organ-confined and well differentiated in node-positive disease (Gleason score ⬍ or ⫽ 6) the biochemical relapse rate was lower than in men with higher tumour stage and grade. Conclusions: When dissecting pelvic lymph nodes, extended or sentinel lymphadenectomy should be preferred. Removing the diseased nodes could improve the PSA progression-free survival, especially in well differentiated organ-confined disease.
Commentary This study used intraoperative scintigraphic imaging to identify potentially positive lymph nodes in men undergoing radical prostatectomy for low-risk prostate cancer. By using more meticulous pathologic examination, the authors were able to identify lymph node metastases in 7% of these patients, which is marginally higher than what would have been predicted using published nomograms. The largest subset of the patients (34.5%) had positive nodes along the internal iliac artery. These data highlight the need to perform a large field node dissection in prostate cancer and the potential use of intraoperative imaging in identifying those patients with node positive disease. doi:10.1016/j.urolonc.2006.11.004 Badrinath Konety, M.D., M.B.A. Incidence of initial local therapy among men with lower-risk prostate cancer in the United States. Miller DC, Gruber SB, Hollenbeck BK, Montie JE, Wei JT, Department of Urology, University of Michigan, Ann Arbor, MI. J Natl Cancer Inst 2006;98:1134 – 41 Background: The frequently indolent nature of early-stage prostate cancer in older men and in men with low- or moderate-grade tumors and the demonstration that the survival benefits of radical prostatectomy are primarily among men younger than 65 years have led to concerns about prostate cancer overtreatment. Methods: Using data from 13 Surveillance, Epidemiology, and End Results registries, we performed a retrospective cohort study of 71,602 men who were diagnosed with localized or regional prostate cancer between 2000 and 2002. We quantified the incidence of initial curative therapy (i.e., surgery or radiation therapy) among men with lower-risk cancers as defined by their limited likelihood of either dying from expectantly managed prostate cancer or achieving a survival benefit from local therapy. Stratified analyses and multinomial logistic regression models were used to quantify the absolute and relative rates of curative therapy among men in various age-grade strata. All statistical tests were two-sided. Results: We identified 24,405 men with lower-risk prostate cancers and complete data for the first course of treatment. Initial curative therapy was undertaken in 13,537 of these men (55%); 81% of treated men received radiation therapy. The likelihood of curative therapy, relative to expectant management, varied statistically significantly among lower-risk age-grade strata (all P ⬍ .05). Assuming that initial expectant management is appropriate for all lower-risk cancers, 2564 men (10%) in this population-based sample were overtreated with radical prostatectomy and 10,973 (45%) with radiation therapy. Conclusions: These data quantify a target population for whom greater use of expectant approaches may reduce overtreatment and improve the quality of localized prostate cancer care.
Commentary These authors conducted a retrospective analysis of treatment patterns for lower risk prostate cancer using the Surveillance, Epidemiology, and End Results data set, and compared trends over 2 time periods, 10 years apart. The definition of lower risk disease was basically
K. Anderson / Urologic Oncology: Seminars and Original Investigations 25 (2007) 87–95
93
based on grade of tumor and patient age, which adopts a more patient-centered approach, rather than a disease-focused approach of most conventional risk stratification schema. It is interesting to note that high rates of curative therapy, mainly radiation therapy, were observed in patients with low-risk disease. Although radical prostatectomy was age sensitive, radiation therapy use did not change with age, even beyond 75 years when treatment value is very questionable. This result may be fostered by an impression that these men better tolerated radiation therapy. However, that still does not justify overtreatment. Most interestingly, the rate of expectant management/androgen deprivation therapy for men with poorly differentiated cancer was higher than that for moderately differentiated tumors. This relative underutilization of curative treatment is hard to explain. It is possible that this may be a gross overestimation, given that many men may have received neoadjuvant hormonal therapy, followed by radiation, which is not captured in the Surveillance, Epidemiology, and End Results database. Although it is to be acknowledged that single modality curative therapy is not uniformly effective in men with high Gleason tumors, the efficacy is not so low as to justify switching to expectant treatment or primary androgen deprivation therapy. doi:10.1016/j.urolonc.2006.11.005 Badrinath Konety, M.D., M.B.A.
LABORATORY RESEARCH Comparison of holding strength of suture anchors for hepatic and renal parenchyma. Ames CD, Perrone JM, Frisella AJ, Morrissey K, Landman J, Division of Urology, Washington University School of Medicine, St. Louis, MO. J Endourol 2005;19:1221–5 Background and Purpose: Various laparoscopic devices have been described for suture anchoring during solid organ parenchymal closure. Application of these devices expedites the closure of parenchymal defects and minimizes ischemia time. We compared different technologies as suture anchors for parenchymal closure. Materials and Methods: A tensometer was used to determine the amount of tension necessary to dislodge each of five different clips from Vicryl suture alone or against two different substrates (fresh pig kidney and liver) with and without an intervening pledget. The clips investigated were the Lapra-Ty (Ethicon), Endoclip II (US Surgical), small Horizon Ligating Clips (Weck), Hem-o-lok Medium Polymer Clips (Weck), and a novel Suture-clip (Applied Medical). ANOVA and two-sided Fisher’s exact test provided statistical analysis. Results: The force required to dislodge the Lapra-Ty clip from bare suture for both 0 and 1 Vicryl (7.0 N) was approximately fourfold the force required to dislodge the Endoclips or the 5-mm or 10-mm Hem-o-lok clips (p⬍0.01). When clips were applied to suture running through renal or liver parenchyma, the novel Suture-clip required the greatest tension to dislodge (P⬍0.01), followed by the Horizon and Lapra-Ty clips. There were no statistically significant differences in the tension required to dislodge a given clip from the two parenchymal substrates or in the presence or absence of a pledget. Conclusions: In our experimental model, the Suture-clip, Lapra-Ty, and Horizon clips required significantly greater tension to dislodge than the Hem-o-lok and Endoclip clips. The addition of a pledget did not improve tension resistance. Commentary Although laparoscopic knot tying is a skill that can be learned through repetition in a dry lab, the use of this technique for laparoscopic partial nephrectomy can make for a challenging and often rather frustrating time in the operating room. Laparoscopic approximation of renal tissue through tensioning of sutures over bolsters is difficult enough but then to tie a knot while maintaining adequate tension may require an assistant to “hold” the knot while the second throw is prepared. To overcome this problem, a number of suture anchoring devices have been developed to obviate the need for knot tying. In this article, Ames et al. evaluated suture anchoring devices and found that of the commercially available anchors, both the Horizon Ligating Clips and the Lapra-Ty held suture well enough to resist suture tensioning forces great enough to cause renal parenchymal tearing. Although these anchors were not compared against a traditional surgical knot, any anchor that can hold a suture against tension sufficient to tear through the renal parenchyma is likely adequate for use during laparoscopic partial nephrectomy. Interestingly, there was an equal frequency of parenchymal tearing whether or not a Surgicel pledget was inserted between the anchor and the parenchyma. Although the use of these devices has been previously reported in small clinical series, this report should help alleviate any doubt about the effectiveness of these devices for use during partial nephrectomy. Despite the proliferation of hemostatic agents and energy based coagulation devices (ultrasonic shears, radiofrequency based coagulation, etc.), there are currently no well-proven alternatives to sutured repairs (generally with bolsters) following large and deep partial nephrectomy resections. The Horizon Ligating Clip or Lapra-Ty make repair after this type of laparoscopic partial nephrectomy significantly more rapid than can be achieved with knot tying. doi:10.1016/j.urolonc.2006.08.023 Kyle Anderson, M.D. Acute integrity of closure for partial nephrectomy: Comparison of 7 agents in a hypertensive porcine model. Johnston WK III, Kelel KM, Hollenbeck BK, Daignault S, Wolf JS Jr, Department of Urology, University of Michigan and Veterans Administration Medical Center, Ann Arbor, MI. J Urol 2006;175:2307-11 Purpose: We assessed the acute effectiveness of closure after partial nephrectomy of 7 techniques in a large hypertensive porcine model using shallow and deep resections to approximate clinical situations.