- Email: [email protected]
Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer
EUF-207; No. of Pages 2 EUROPEAN UROLOGY FOCUS XXX (2016) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com/eufocus
Clinical Case Discussion
Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer Axel Heidenreich * Department of Urology, Uro-Oncology, Reconstructive and Robot-assisted Surgery, University of Cologne, Cologne, Germany
Based on the data given in the case report we face a patient who is suffering from castration-resistant, locally progressive, and lymph node-positive prostate cancer with significant local cancer—associated morbidity such as voiding dysfunction and gross hematuria necessitating repetitive blood transfusions. Urethrocystoscopy revealed bleeding vessels in the prostatic urethra which are most probably due to cancer infiltration. The bladder appeared without significant pathologies in terms of bladder neck infiltration. Unfortunately, we do not have additional information with regard to the volume of the prostate and the local extent of prostate cancer usually assessed with multiparametric magnetic resonance imaging (MRI). Based on the given information and the good performance status of the patient, active local treatment needs to be performed in order to prevent bladder neck infiltration, upper urinary tract dilatation, and ongoing gross hematuria. Treatment options are external beam radiation or palliative transurethral resection of the prostate, followed by external beam radiotherapy/intensity modulated radiation therapy or palliative radical prostatectomy, and eventually cystoprostatectomy. Given the fact that the patient: (1) had a poor prostatespecific antigen (PSA) response to luteinizing hormonereleasing hormone treatment with PSA serum concentrations well above 4 ng/ml, (2) developed PSA and local progression just 1 yr after initiation of treatment, (3) experienced repetitive transfusion-requiring hematuria, and (4) had undifferentiated prostate cancer cells. Palliative radical surgery is associated with the best long-term response compared with nonradical treatment options. In our experience on 65 highly selected patients, patients will
survive 85% of their remaining life time without any local symptoms after radical palliative surgery [1]. However, radiation therapy is associated with a high risk of Grade 3/4 toxicities in about 10% of the patients and a high risk of local progression remains [2,3]. 1.
Preoperative evaluation of the patient
Prior to the decision-making process of radical palliative surgery, a multiparametric MRI of the prostate and the pelvic floor should be performed in order to assess the local extent of the prostate with special emphasis of the areas of extraprostatic growth, the exclusion of pelvic floor infiltration, and the presence of an at least minimal tissue plane between the prostate and the anterior surface of the rectum. If the MRI demonstrates broad infiltration of the pelvic floor, the patient usually is not a good candidate for palliative surgery since macroscopically positive resection margins will remain resulting in persisting pain, rapid local progression, and significantly increased local complications. Those patients are best managed using mere palliative procedures such as a combination of palliative transurethral resection of the prostate and radiation therapy or even intravesical formalin instillations to stop recurrent bleeding [4,5]. Another prerequisite to performing palliative radical (cysto-)prostatectomy is the selection of patients. Patients need to be in a good general performance status of Eastern Cooperative Oncology Group 0–1. Serum concentrations of albumin and C-reactive protein (CRP) determined preoperatively should be within the normal range. Low albumin levels are an indicator of malnutrition which has been
* Corresponding author. Department of Urology, Uro-Oncology, Specialized and Robot-assisted Urology, University of Cologne, Kerpener Street 62, Aachen, Cologne 50937, Germany. Tel. +4922147882108; Fax: +492418082441. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.euf.2016.08.009 2405-4569/# 2016 Published by Elsevier B.V. on behalf of European Association of Urology.
Please cite this article in press as: Heidenreich A, Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer. Eur Urol Focus (2016), http://dx.doi.org/10.1016/j.euf.2016.08.009
EUF-207; No. of Pages 2 2
EUROPEAN UROLOGY FOCUS XXX (2016) XXX–XXX
shown to be associated with a higher frequency of complications following radical cystectomy [6]. If possible, patients need to be supported with supplementary nutrition for 3–4 wk preoperatively. It also has been shown that specialized immunonutrition is associated with a significant 33% reduction in postoperative complication rates and a 39% reduction in infection rates [7]. CRP serum levels are often elevated due to paraneoplastic activation of an immunocascade triggered interleukins 2, 6, and 8 [8,9]. It has been shown in various studies that elevated CRP serum concentrations are associated with a poor cancer-specific survival in bladder cancer and metastatic prostate cancer [10–12]. In fact, we always observed a significant CRP serum level in the few patients who progressed very shortly after radical palliative surgery.
The average hospitalization time was 14 (10–23) d. A long-term reduction of symptoms was observed in 80% of the patients. 4.
Treatment outcome
A long-term reduction of symptoms occurred in 53/65 patients (80%). After a mean follow-up time of 27 (3–42) mo, the symptom-free survival rate was 15.3 (1–25) mo and the mean survival rate was 20.4 (1–28) mo. Conflicts of interest: The author has nothing to disclose.
References [1] Heidenreich A, Porres D, Pfister D. the role of palliative surgery in
2.
Surgical strategy
castration-resistant prostate cancer. Oncol Res Treat 2015;38: 670–7. [2] White R, Khor R, Bressel M, et al. Efficacy of high-dose palliative
Since the patient most probably will have bladder neck infiltration, he needs to be counseled for both radical prostatectomy and radical cystoprostatectomy with a urinary diversion. We always perform intraoperative frozen section analysis of biopsies from the bladder neck and the prostatic apex in such cases. If the biopsy of the bladder neck is positive, we always proceed with a radical cystectomy. In fact, 80% of our patients required a radical cystectomy due to microscopic infiltration of the bladder neck. With regard to urinary diversion, the majority of patients have received an ileal conduit due to the extent of the disease. Ten percent underwent radical prostatectomy only and another 10% required both anterior and posterior exenteration with an ileal conduit and a permanent colostomy. However, as we mentioned earlier, the symptom-free survival after these palliative procedures covered 80% of the remaining life time.
radiotherapy for localized, castration-resistant prostate cancer. Clin Oncol (R Coll Radiol) 2015;27:16–21. [3] Won AC, Gurney H, Marx G, De Souza P, Patel MI. Primary treatment of the prostate improves local palliation in men who ultimately develop castrate-resistant prostate cancer. BJU Int 2013;112: E250–5. [4] Crain DS, Amling CL, Kane CJ. Palliative transurethral prostate resection for bladder outlet obstruction in patients with locally advanced prostate cancer. J Urol 2004;171:668–71. [5] Ghahestani SM, Shakhssalim N. Palliative treatment of intractable hematuria in context of advanced bladder cancer: A systematic review. Urol J 2009;6:149–56. [6] Johnson DC, Riggs SB, Nielsen ME, et al. Nutritional predictors of complications following radical cystectomy. World J Urol 2015; 33:1129–37. [7] Hamilton-Reeves JM, Bechtel MD, Hand LK, et al. Effects of immunonutrition for cystectomy on immune response and infection rates: A pilot randomized controlled clinical trial. Eur Urol 2016; 69:389–92. [8] DeNardo DG, Johansson M, Coussens LM. Immune cells as media-
3.
Complications
tors of solid tumor metastasis. Cancer Metastasis Rev 2008;27: 11–8.
Surgery itself was not significantly more complicated than a normal radical prostatectomy or cystoprostatectomy. The average operation time was 230 (150–430) min with an average blood loss of 450 (400–700) ml. One patient required a transfusion of four erythrocyte packages preoperatively due to excessive preoperative gross hematuria. No significant intraoperative complications were encountered. In the postoperative interval, three ClavienDindo Grade IIIA/B complications required intervention: an intrapelvic abscess, a symptomatic lymphocele, and an obstructive pyonephrosis. In three cases, a paralytic ileus was treated using conservative measures.
[9] Aggarwal BB, Gehlot P. Inflammation and cancer: How friendly is the relationship for cancer patients? Curr Opin Pharmacol 2009;9: 351–69. [10] Xu L, Zhao Q, Huang S, Li S, Wang J, Li Q. Serum C-reactive protein acted as a prognostic biomarker for overall survival in metastatic prostate cancer patients. Tumour Biol 2014;36:669–73. [11] Allin KH, Bojesen SE, Nordestgaard BG. Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 2009;27:2217–24. [12] Stein B, Schrader AJ, Wegener G, Seidel C, Kuczyk MA, Steffens S. Preoperative serum C-reactive protein: A prognostic marker in patients with upper urinary tract urothelial carcinoma. BMC Cancer 2013;13:101.
Please cite this article in press as: Heidenreich A, Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer. Eur Urol Focus (2016), http://dx.doi.org/10.1016/j.euf.2016.08.009
available at www.sciencedirect.com journal homepage: www.europeanurology.com/eufocus
Clinical Case Discussion
Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer Axel Heidenreich * Department of Urology, Uro-Oncology, Reconstructive and Robot-assisted Surgery, University of Cologne, Cologne, Germany
Based on the data given in the case report we face a patient who is suffering from castration-resistant, locally progressive, and lymph node-positive prostate cancer with significant local cancer—associated morbidity such as voiding dysfunction and gross hematuria necessitating repetitive blood transfusions. Urethrocystoscopy revealed bleeding vessels in the prostatic urethra which are most probably due to cancer infiltration. The bladder appeared without significant pathologies in terms of bladder neck infiltration. Unfortunately, we do not have additional information with regard to the volume of the prostate and the local extent of prostate cancer usually assessed with multiparametric magnetic resonance imaging (MRI). Based on the given information and the good performance status of the patient, active local treatment needs to be performed in order to prevent bladder neck infiltration, upper urinary tract dilatation, and ongoing gross hematuria. Treatment options are external beam radiation or palliative transurethral resection of the prostate, followed by external beam radiotherapy/intensity modulated radiation therapy or palliative radical prostatectomy, and eventually cystoprostatectomy. Given the fact that the patient: (1) had a poor prostatespecific antigen (PSA) response to luteinizing hormonereleasing hormone treatment with PSA serum concentrations well above 4 ng/ml, (2) developed PSA and local progression just 1 yr after initiation of treatment, (3) experienced repetitive transfusion-requiring hematuria, and (4) had undifferentiated prostate cancer cells. Palliative radical surgery is associated with the best long-term response compared with nonradical treatment options. In our experience on 65 highly selected patients, patients will
survive 85% of their remaining life time without any local symptoms after radical palliative surgery [1]. However, radiation therapy is associated with a high risk of Grade 3/4 toxicities in about 10% of the patients and a high risk of local progression remains [2,3]. 1.
Preoperative evaluation of the patient
Prior to the decision-making process of radical palliative surgery, a multiparametric MRI of the prostate and the pelvic floor should be performed in order to assess the local extent of the prostate with special emphasis of the areas of extraprostatic growth, the exclusion of pelvic floor infiltration, and the presence of an at least minimal tissue plane between the prostate and the anterior surface of the rectum. If the MRI demonstrates broad infiltration of the pelvic floor, the patient usually is not a good candidate for palliative surgery since macroscopically positive resection margins will remain resulting in persisting pain, rapid local progression, and significantly increased local complications. Those patients are best managed using mere palliative procedures such as a combination of palliative transurethral resection of the prostate and radiation therapy or even intravesical formalin instillations to stop recurrent bleeding [4,5]. Another prerequisite to performing palliative radical (cysto-)prostatectomy is the selection of patients. Patients need to be in a good general performance status of Eastern Cooperative Oncology Group 0–1. Serum concentrations of albumin and C-reactive protein (CRP) determined preoperatively should be within the normal range. Low albumin levels are an indicator of malnutrition which has been
* Corresponding author. Department of Urology, Uro-Oncology, Specialized and Robot-assisted Urology, University of Cologne, Kerpener Street 62, Aachen, Cologne 50937, Germany. Tel. +4922147882108; Fax: +492418082441. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.euf.2016.08.009 2405-4569/# 2016 Published by Elsevier B.V. on behalf of European Association of Urology.
Please cite this article in press as: Heidenreich A, Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer. Eur Urol Focus (2016), http://dx.doi.org/10.1016/j.euf.2016.08.009
EUF-207; No. of Pages 2 2
EUROPEAN UROLOGY FOCUS XXX (2016) XXX–XXX
shown to be associated with a higher frequency of complications following radical cystectomy [6]. If possible, patients need to be supported with supplementary nutrition for 3–4 wk preoperatively. It also has been shown that specialized immunonutrition is associated with a significant 33% reduction in postoperative complication rates and a 39% reduction in infection rates [7]. CRP serum levels are often elevated due to paraneoplastic activation of an immunocascade triggered interleukins 2, 6, and 8 [8,9]. It has been shown in various studies that elevated CRP serum concentrations are associated with a poor cancer-specific survival in bladder cancer and metastatic prostate cancer [10–12]. In fact, we always observed a significant CRP serum level in the few patients who progressed very shortly after radical palliative surgery.
The average hospitalization time was 14 (10–23) d. A long-term reduction of symptoms was observed in 80% of the patients. 4.
Treatment outcome
A long-term reduction of symptoms occurred in 53/65 patients (80%). After a mean follow-up time of 27 (3–42) mo, the symptom-free survival rate was 15.3 (1–25) mo and the mean survival rate was 20.4 (1–28) mo. Conflicts of interest: The author has nothing to disclose.
References [1] Heidenreich A, Porres D, Pfister D. the role of palliative surgery in
2.
Surgical strategy
castration-resistant prostate cancer. Oncol Res Treat 2015;38: 670–7. [2] White R, Khor R, Bressel M, et al. Efficacy of high-dose palliative
Since the patient most probably will have bladder neck infiltration, he needs to be counseled for both radical prostatectomy and radical cystoprostatectomy with a urinary diversion. We always perform intraoperative frozen section analysis of biopsies from the bladder neck and the prostatic apex in such cases. If the biopsy of the bladder neck is positive, we always proceed with a radical cystectomy. In fact, 80% of our patients required a radical cystectomy due to microscopic infiltration of the bladder neck. With regard to urinary diversion, the majority of patients have received an ileal conduit due to the extent of the disease. Ten percent underwent radical prostatectomy only and another 10% required both anterior and posterior exenteration with an ileal conduit and a permanent colostomy. However, as we mentioned earlier, the symptom-free survival after these palliative procedures covered 80% of the remaining life time.
radiotherapy for localized, castration-resistant prostate cancer. Clin Oncol (R Coll Radiol) 2015;27:16–21. [3] Won AC, Gurney H, Marx G, De Souza P, Patel MI. Primary treatment of the prostate improves local palliation in men who ultimately develop castrate-resistant prostate cancer. BJU Int 2013;112: E250–5. [4] Crain DS, Amling CL, Kane CJ. Palliative transurethral prostate resection for bladder outlet obstruction in patients with locally advanced prostate cancer. J Urol 2004;171:668–71. [5] Ghahestani SM, Shakhssalim N. Palliative treatment of intractable hematuria in context of advanced bladder cancer: A systematic review. Urol J 2009;6:149–56. [6] Johnson DC, Riggs SB, Nielsen ME, et al. Nutritional predictors of complications following radical cystectomy. World J Urol 2015; 33:1129–37. [7] Hamilton-Reeves JM, Bechtel MD, Hand LK, et al. Effects of immunonutrition for cystectomy on immune response and infection rates: A pilot randomized controlled clinical trial. Eur Urol 2016; 69:389–92. [8] DeNardo DG, Johansson M, Coussens LM. Immune cells as media-
3.
Complications
tors of solid tumor metastasis. Cancer Metastasis Rev 2008;27: 11–8.
Surgery itself was not significantly more complicated than a normal radical prostatectomy or cystoprostatectomy. The average operation time was 230 (150–430) min with an average blood loss of 450 (400–700) ml. One patient required a transfusion of four erythrocyte packages preoperatively due to excessive preoperative gross hematuria. No significant intraoperative complications were encountered. In the postoperative interval, three ClavienDindo Grade IIIA/B complications required intervention: an intrapelvic abscess, a symptomatic lymphocele, and an obstructive pyonephrosis. In three cases, a paralytic ileus was treated using conservative measures.
[9] Aggarwal BB, Gehlot P. Inflammation and cancer: How friendly is the relationship for cancer patients? Curr Opin Pharmacol 2009;9: 351–69. [10] Xu L, Zhao Q, Huang S, Li S, Wang J, Li Q. Serum C-reactive protein acted as a prognostic biomarker for overall survival in metastatic prostate cancer patients. Tumour Biol 2014;36:669–73. [11] Allin KH, Bojesen SE, Nordestgaard BG. Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 2009;27:2217–24. [12] Stein B, Schrader AJ, Wegener G, Seidel C, Kuczyk MA, Steffens S. Preoperative serum C-reactive protein: A prognostic marker in patients with upper urinary tract urothelial carcinoma. BMC Cancer 2013;13:101.
Please cite this article in press as: Heidenreich A, Palliative Radical (Cysto-)prostatectomy for Locally Advanced, Symptomatic Castration-resistant Prostate Cancer. Eur Urol Focus (2016), http://dx.doi.org/10.1016/j.euf.2016.08.009