Case Report
Urologia Internationalis
Received: July 22, 2013 Accepted after revision: October 28, 2013 Published online: September 6, 2014
Urol Int DOI: 10.1159/000356990
Salvage Pelvic Lymph Node Dissection after Radical Prostatectomy for Biochemical and Lymph Node Recurrence Charlotte Peeters a Diederik Ponette b Hendrik van Poppel a Department of Urology, UZ Gasthuisberg, Leuven, and b Department of Urology, AZ Damiaan, Ostend, Belgium
Key Words Salvage pelvic lymph node dissection · Radical prostatectomy · Biochemical recurrence · Lymph node recurrence
Abstract Prostate cancer is the most common male malignancy. Radiation therapy and radical prostatectomy are the main curative treatment options for organ confined disease. Despite the good long-term oncologic outcomes, roughly 40% of patients undergoing surgery develop biochemical recurrence, manifested as a rising prostate-specific antigen (PSA). Those patients are at higher risk of developing a local or distant recurrence. The diagnosis of a nodal recurrence is challenging. This report is about a 66-year-old male, who had a radical prostatectomy in 2006. Postoperatively, the PSA was never undetectable. Radiotherapy was delivered in 2007, but the PSA rose again. Anti-androgen therapy was started, but he developed painful mastodynia. A (11C) choline PET-CT showed an enlarged suspicious lymph node at the left common iliac and a salvage pelvic lymphadenectomy was performed. Postoperatively, the PSA remained undetectable for the last 5 years. The use of lesion – targeted therapy for oligometastatic disease is a new concept in urology, aiming at reducing the tumor burden. Therefore, even though this surgical approach might not be associated with a durable response over time, the tumor load is decreased and further cancer progression might be delayed, allowing to postpone the delivery of hormone therapy. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0042–1138/14/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/uin
Introduction
Prostate cancer (PCa) is the most common male malignancy. According to the recent European Association of Urology (EAU) guidelines, radiation therapy and radical prostatectomy are the main curative treatment options for organ-confined disease. Despite the good longterm oncologic outcomes provided by radical prostatectomy for clinically localized PCa, roughly 40% of patients undergoing surgery develop biochemical recurrence (BCR) [1], manifested as rising prostate-specific antigen (PSA). Although only approximately 15% of patients with BCR after radical prostatectomy will die from PCa [2], patients with BCR are at higher risk of developing local or distant recurrence. A correct diagnosis of the site of PCa recurrence is most important in the clinical decisionmaking process. Patients presenting with a local recurrence are usually treated with salvage radiotherapy. Conversely, patients with distant recurrence are treated with hormone therapy (HT) [3]. The diagnosis of nodal recurrence is challenging. Conventional imaging such as computed tomography (CT) or magnetic resonance imaging has low sensitivity in the detection of nodal recurrence [4]. However, new techniques have been introduced, such as 11C-choline positron emission tomography (PET)-CT. This has shown very good sensitivity and specificity for detecting PCa nodal recurrence [5].
Charlotte Peeters Department of Urology, UZ Gasthuisberg Herestraat 49 BE–3000 Leuven (Belgium) E-Mail [email protected]
Downloaded by: Gazi Üniversitesi 198.143.58.1 - 4/13/2016 9:31:24 AM
a
Color version available online
Color version available online
Fig. 1. Drawing of the salvage lymphadenectomy as performed in
Fig. 2. Intraoperative view showing the aorta and vena cava bifur-
September 2009.
cation after resection of the para-aortic and presacral nodes.
The EAU guidelines recommend early or delayed HT for nodal metastasis. However, the secondary effects of this treatment affect quality of life and cause, next to others, cardiovascular morbidity [6]. This would suggest that removal of positive lymph nodes might impact on cancer progression and eventually delay and/or reduce exposure to HT.
nodes of the left and right common iliac and internal iliac, the paraaortic and the presacral area (fig. 1, 2). In the postoperative period, there was a prolonged drainage of lymphatic fluid that stopped spontaneously. A small lymphocele caused a mild hydroureteronephrosis of the left kidney which did not need any treatment. The pathologist reported on ten lymph nodes, a small node being positive in the para-aortic area, and one macrometastasis in the presacral area. The first postoperative PSA was 0; 5 years after the salvage lymphadenectomy, the PSA remains undetectable (fig. 3).
Case Report
2
Urol Int DOI: 10.1159/000356990
Discussion
This is a case report of PSA persistence and increase after radical prostatectomy and salvage radiotherapy to the prostate bed. At a PSA of 0.56 ng/ml, 11C-choline PET-CT was performed, which showed a suspect lymph node. A salvage lymphadenectomy was performed showing two positive lymph nodes. The patient has complete biochemical response with an undetectable PSA after nearly 5 years. His quality of life improved since he stopped the anti-androgen therapy. Rigatti et al. [7] showed that salvage lymphadenectomy is feasible in patients with BCR after radical prostatectomy and nodal pathological uptake at 11C-choline PET-CT scan. However, the benefit related to biochemical response was not durable over time because the majority of patients still developed BCR after a median time of 18 months. However, despite this apparent lack of benefit in the BCR-free survival rates, the authors showed that when Peeters /Ponette /van Poppel
Downloaded by: Gazi Üniversitesi 198.143.58.1 - 4/13/2016 9:31:24 AM
A 66-year-old male patient underwent bilateral nerve-sparing radical prostatectomy with obturator lymphadenectomy in August 2006 for an intermediate-risk PCa with negative CT and bone scan, an initial PSA of 8 ng/ml, pT2c N0, Gleason 7, with negative surgical margins. The postoperative PSA was 0.11 ng/ml. At the next control PSA was 0.17 ng/ml, and a wait-and-see attitude was adopted. Three months later, PSA had almost doubled up to 0.36 ng/ml. A restaging abdominal CT scan showed no suspect lymph nodes or bone metastasis. In October 2007, radiotherapy was delivered to the prostatic fossa in a dose of 66 Gy. The PSA control after radiotherapy was still 0.22 ng/ml. 10 months later, PSA rose again up to 0.38 ng/ml and then to 0.49 ng/ml. After two times 6 Gy radiation of the breasts, bicalutamide (Casodex®) was started. The patient however developed painful gynecomastia while the PSA decreased slowly to 0.18 ng/ml. Bicalutamide was stopped because of severe mastodynia. The PSA rose again up to 0.56 ng/ml and restaging by 11C-choline PET-CT was performed. This showed an enlarged suspicious lymph node in the left common iliac area not seen on previous CT scans. After discussion with the patient, informed consent was obtained and salvage lymphadenectomy was performed 3 years after radical prostatectomy. The lymphadenectomy comprised the lymph
PSA
RP
Casodex 150 mg
RT 66 Gy
Stop Casodex
Color version available online
PSA
9 8 7 6 5 4 3 2 1 0
Salvage LND
08 2006
12 2006
03 2007
06 2007
12 2007
03 2008
08 2008
11 2008
02 2009
05 2009
09 2009
03 2010
08 2010
02 2011
08 2011
02 2012
08 2012
02 2013
7.9
0.11
0.17
0.36
0.22
0.22
0.38
0.49
0.48
0.18
0.56
0
0
0
0
0
0
0
Fig. 3. PSA course during the patient’s history. RP = Radical prostatectomy; RT = radiation therapy; LND = lymph
node dissection.
recurrent cancer in the nodes could be resected, roughly 35% of patients showed absence of any further clinical progression at 5-year follow-up. The predictive factors for a biochemical response of salvage lymphadenectomy are a PSA 24 months and an initial node-negative status at pelvic lymphadenectomy during primary radical prostatectomy. The sensitivity and specificity of 11C-choline PET-CT scan as a diagnostic tool is not optimal, but nowadays there is no other diagnostic tool. Performing salvage lymphadenectomy without any positive imaging for a lymph node recurrence cannot yet be supported. The use of lesion-targeted therapy for oligometastatic disease is a new concept in urology, aiming at reducing the tumor burden. Therefore, even though this surgical approach might not be associated with durable response over time, the tumor load is anyhow decreased and further can-
cer progression might be delayed, allowing to postpone the delivery of HT. When a salvage lymphadenectomy is performed, it has to be an extended lymphadenectomy in order to remove possible other micrometastatic deposits. This is necessary because the affected lymph nodes of PCa can indeed vary in number and localization [8].
Conclusion
Salvage lymphadenectomy is feasible in patients with BCR after radical prostatectomy with suspicious lymph nodes on 11C-choline PET-CT. An extended lymphadenectomy has to be performed. Although most patients will ultimately progress with BCR, this approach is aimed at delaying the clinical progression and at postponing the need for administration of HT.
References
Salvage Pelvic Lymph Node Dissection after Radical Prostatectomy
4 Sandler HM, Eisenberger MA: Assessing and treating patients with increasing prostate specific antigen following radical prostatectomy. J Urol 2007;178:S20–S24. 5 Picchio M, Briganti A, Fanti S, Heidenreich A, Krause BJ, Messa C, Montorsi F, Reske SN, Thalmann GN: The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol 2011;59:51–60. 6 Dacal K, Sereika SM, Greenspan SL: Quality of life in prostate cancer patients taking androgen deprivation therapy. J Am Geriatr Soc 2006;54:85–90.
Urol Int DOI: 10.1159/000356990
7 Rigatti P, Suardi N, Briganti A, Da Pozzo LF, Tutolo M, Villa L, Gallina A, Capitanio U, Abdollah F, Scattoni V, Colombo R, Freschi M, Picchio M, Messa C, Guazzoni G, Montorsi F: Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol 2011;60:935–943. 8 Mattei A, Fuechsel FG, Bhatta Dhar N, Warncke SH, Thalmann GN, Krause T, Studer UE: The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol 2008;53:118–125.
3
Downloaded by: Gazi Üniversitesi 198.143.58.1 - 4/13/2016 9:31:24 AM
1 Han M, Partin AW, Pound CR, Epstein JI, Walsh PC: Long-term biochemical diseasefree and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001;28:555–565. 2 Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591–1597. 3 Mottet N, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, Schmid HP, van der Kwast T, Wiegel T, Zattoni F, Heidenreich A: EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castrationresistant prostate cancer. Eur Urol 2011; 59: 572–583.
Urologia Internationalis
Received: July 22, 2013 Accepted after revision: October 28, 2013 Published online: September 6, 2014
Urol Int DOI: 10.1159/000356990
Salvage Pelvic Lymph Node Dissection after Radical Prostatectomy for Biochemical and Lymph Node Recurrence Charlotte Peeters a Diederik Ponette b Hendrik van Poppel a Department of Urology, UZ Gasthuisberg, Leuven, and b Department of Urology, AZ Damiaan, Ostend, Belgium
Key Words Salvage pelvic lymph node dissection · Radical prostatectomy · Biochemical recurrence · Lymph node recurrence
Abstract Prostate cancer is the most common male malignancy. Radiation therapy and radical prostatectomy are the main curative treatment options for organ confined disease. Despite the good long-term oncologic outcomes, roughly 40% of patients undergoing surgery develop biochemical recurrence, manifested as a rising prostate-specific antigen (PSA). Those patients are at higher risk of developing a local or distant recurrence. The diagnosis of a nodal recurrence is challenging. This report is about a 66-year-old male, who had a radical prostatectomy in 2006. Postoperatively, the PSA was never undetectable. Radiotherapy was delivered in 2007, but the PSA rose again. Anti-androgen therapy was started, but he developed painful mastodynia. A (11C) choline PET-CT showed an enlarged suspicious lymph node at the left common iliac and a salvage pelvic lymphadenectomy was performed. Postoperatively, the PSA remained undetectable for the last 5 years. The use of lesion – targeted therapy for oligometastatic disease is a new concept in urology, aiming at reducing the tumor burden. Therefore, even though this surgical approach might not be associated with a durable response over time, the tumor load is decreased and further cancer progression might be delayed, allowing to postpone the delivery of hormone therapy. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0042–1138/14/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/uin
Introduction
Prostate cancer (PCa) is the most common male malignancy. According to the recent European Association of Urology (EAU) guidelines, radiation therapy and radical prostatectomy are the main curative treatment options for organ-confined disease. Despite the good longterm oncologic outcomes provided by radical prostatectomy for clinically localized PCa, roughly 40% of patients undergoing surgery develop biochemical recurrence (BCR) [1], manifested as rising prostate-specific antigen (PSA). Although only approximately 15% of patients with BCR after radical prostatectomy will die from PCa [2], patients with BCR are at higher risk of developing local or distant recurrence. A correct diagnosis of the site of PCa recurrence is most important in the clinical decisionmaking process. Patients presenting with a local recurrence are usually treated with salvage radiotherapy. Conversely, patients with distant recurrence are treated with hormone therapy (HT) [3]. The diagnosis of nodal recurrence is challenging. Conventional imaging such as computed tomography (CT) or magnetic resonance imaging has low sensitivity in the detection of nodal recurrence [4]. However, new techniques have been introduced, such as 11C-choline positron emission tomography (PET)-CT. This has shown very good sensitivity and specificity for detecting PCa nodal recurrence [5].
Charlotte Peeters Department of Urology, UZ Gasthuisberg Herestraat 49 BE–3000 Leuven (Belgium) E-Mail [email protected]
Downloaded by: Gazi Üniversitesi 198.143.58.1 - 4/13/2016 9:31:24 AM
a
Color version available online
Color version available online
Fig. 1. Drawing of the salvage lymphadenectomy as performed in
Fig. 2. Intraoperative view showing the aorta and vena cava bifur-
September 2009.
cation after resection of the para-aortic and presacral nodes.
The EAU guidelines recommend early or delayed HT for nodal metastasis. However, the secondary effects of this treatment affect quality of life and cause, next to others, cardiovascular morbidity [6]. This would suggest that removal of positive lymph nodes might impact on cancer progression and eventually delay and/or reduce exposure to HT.
nodes of the left and right common iliac and internal iliac, the paraaortic and the presacral area (fig. 1, 2). In the postoperative period, there was a prolonged drainage of lymphatic fluid that stopped spontaneously. A small lymphocele caused a mild hydroureteronephrosis of the left kidney which did not need any treatment. The pathologist reported on ten lymph nodes, a small node being positive in the para-aortic area, and one macrometastasis in the presacral area. The first postoperative PSA was 0; 5 years after the salvage lymphadenectomy, the PSA remains undetectable (fig. 3).
Case Report
2
Urol Int DOI: 10.1159/000356990
Discussion
This is a case report of PSA persistence and increase after radical prostatectomy and salvage radiotherapy to the prostate bed. At a PSA of 0.56 ng/ml, 11C-choline PET-CT was performed, which showed a suspect lymph node. A salvage lymphadenectomy was performed showing two positive lymph nodes. The patient has complete biochemical response with an undetectable PSA after nearly 5 years. His quality of life improved since he stopped the anti-androgen therapy. Rigatti et al. [7] showed that salvage lymphadenectomy is feasible in patients with BCR after radical prostatectomy and nodal pathological uptake at 11C-choline PET-CT scan. However, the benefit related to biochemical response was not durable over time because the majority of patients still developed BCR after a median time of 18 months. However, despite this apparent lack of benefit in the BCR-free survival rates, the authors showed that when Peeters /Ponette /van Poppel
Downloaded by: Gazi Üniversitesi 198.143.58.1 - 4/13/2016 9:31:24 AM
A 66-year-old male patient underwent bilateral nerve-sparing radical prostatectomy with obturator lymphadenectomy in August 2006 for an intermediate-risk PCa with negative CT and bone scan, an initial PSA of 8 ng/ml, pT2c N0, Gleason 7, with negative surgical margins. The postoperative PSA was 0.11 ng/ml. At the next control PSA was 0.17 ng/ml, and a wait-and-see attitude was adopted. Three months later, PSA had almost doubled up to 0.36 ng/ml. A restaging abdominal CT scan showed no suspect lymph nodes or bone metastasis. In October 2007, radiotherapy was delivered to the prostatic fossa in a dose of 66 Gy. The PSA control after radiotherapy was still 0.22 ng/ml. 10 months later, PSA rose again up to 0.38 ng/ml and then to 0.49 ng/ml. After two times 6 Gy radiation of the breasts, bicalutamide (Casodex®) was started. The patient however developed painful gynecomastia while the PSA decreased slowly to 0.18 ng/ml. Bicalutamide was stopped because of severe mastodynia. The PSA rose again up to 0.56 ng/ml and restaging by 11C-choline PET-CT was performed. This showed an enlarged suspicious lymph node in the left common iliac area not seen on previous CT scans. After discussion with the patient, informed consent was obtained and salvage lymphadenectomy was performed 3 years after radical prostatectomy. The lymphadenectomy comprised the lymph
PSA
RP
Casodex 150 mg
RT 66 Gy
Stop Casodex
Color version available online
PSA
9 8 7 6 5 4 3 2 1 0
Salvage LND
08 2006
12 2006
03 2007
06 2007
12 2007
03 2008
08 2008
11 2008
02 2009
05 2009
09 2009
03 2010
08 2010
02 2011
08 2011
02 2012
08 2012
02 2013
7.9
0.11
0.17
0.36
0.22
0.22
0.38
0.49
0.48
0.18
0.56
0
0
0
0
0
0
0
Fig. 3. PSA course during the patient’s history. RP = Radical prostatectomy; RT = radiation therapy; LND = lymph
node dissection.
recurrent cancer in the nodes could be resected, roughly 35% of patients showed absence of any further clinical progression at 5-year follow-up. The predictive factors for a biochemical response of salvage lymphadenectomy are a PSA 24 months and an initial node-negative status at pelvic lymphadenectomy during primary radical prostatectomy. The sensitivity and specificity of 11C-choline PET-CT scan as a diagnostic tool is not optimal, but nowadays there is no other diagnostic tool. Performing salvage lymphadenectomy without any positive imaging for a lymph node recurrence cannot yet be supported. The use of lesion-targeted therapy for oligometastatic disease is a new concept in urology, aiming at reducing the tumor burden. Therefore, even though this surgical approach might not be associated with durable response over time, the tumor load is anyhow decreased and further can-
cer progression might be delayed, allowing to postpone the delivery of HT. When a salvage lymphadenectomy is performed, it has to be an extended lymphadenectomy in order to remove possible other micrometastatic deposits. This is necessary because the affected lymph nodes of PCa can indeed vary in number and localization [8].
Conclusion
Salvage lymphadenectomy is feasible in patients with BCR after radical prostatectomy with suspicious lymph nodes on 11C-choline PET-CT. An extended lymphadenectomy has to be performed. Although most patients will ultimately progress with BCR, this approach is aimed at delaying the clinical progression and at postponing the need for administration of HT.
References
Salvage Pelvic Lymph Node Dissection after Radical Prostatectomy
4 Sandler HM, Eisenberger MA: Assessing and treating patients with increasing prostate specific antigen following radical prostatectomy. J Urol 2007;178:S20–S24. 5 Picchio M, Briganti A, Fanti S, Heidenreich A, Krause BJ, Messa C, Montorsi F, Reske SN, Thalmann GN: The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol 2011;59:51–60. 6 Dacal K, Sereika SM, Greenspan SL: Quality of life in prostate cancer patients taking androgen deprivation therapy. J Am Geriatr Soc 2006;54:85–90.
Urol Int DOI: 10.1159/000356990
7 Rigatti P, Suardi N, Briganti A, Da Pozzo LF, Tutolo M, Villa L, Gallina A, Capitanio U, Abdollah F, Scattoni V, Colombo R, Freschi M, Picchio M, Messa C, Guazzoni G, Montorsi F: Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol 2011;60:935–943. 8 Mattei A, Fuechsel FG, Bhatta Dhar N, Warncke SH, Thalmann GN, Krause T, Studer UE: The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol 2008;53:118–125.
3
Downloaded by: Gazi Üniversitesi 198.143.58.1 - 4/13/2016 9:31:24 AM
1 Han M, Partin AW, Pound CR, Epstein JI, Walsh PC: Long-term biochemical diseasefree and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001;28:555–565. 2 Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591–1597. 3 Mottet N, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, Schmid HP, van der Kwast T, Wiegel T, Zattoni F, Heidenreich A: EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castrationresistant prostate cancer. Eur Urol 2011; 59: 572–583.
