EURURO-5625; No. of Pages 2 EUROPEAN UROLOGY XXX (2014) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Letter to the Editor NOT referring to a recent journal article Role of Radical Prostatectomy in Metastatic Prostate Cancer: Data from the Munich Cancer Registry In several oncologic entities such as ovarian cancer, colon cancer, and renal cell carcinoma, maximal tumor burden reduction, including resection of the primary tumor, results in a survival benefit and an increased response to systemic
therapy [1–3]. Previously, new data have suggested a survival benefit for radical prostatectomy (RP) in metastatic prostate cancer (M+-PCa) patients. Data from the United States (Surveillance Epidemiology and End Results database) were recently published analyzing the outcomes of men with M+-PCa undergoing RP versus no surgery or radiation therapy (NSR) [4]. Of 8185
Fig. 1 – Survival of patients in the Munich Cancer Registry who did and did not undergo radical prostatectomy: (a) patient cohort, 1998–2010; (b) overall survival in M1 prostate cancer patients. ADT = androgen deprivation therapy; RP = radical prostatectomy; RPE = extraperitoneal radical prostatectomy; XRT = external-beam radiation therapy.
http://dx.doi.org/10.1016/j.eururo.2014.04.009 0302-2838/# 2014 Published by Elsevier B.V. on behalf of European Association of Urology.
Please cite this article in press as: Gratzke C, et al. Role of Radical Prostatectomy in Metastatic Prostate Cancer: Data from the Munich Cancer Registry. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.04.009
EURURO-5625; No. of Pages 2 2
EUROPEAN UROLOGY XXX (2014) XXX–XXX
patients, 7811 (95%) received NSR, whereas 245 (3%) underwent RP. The 5-yr overall survival (OS) and predicted disease-specific survival (DSS) rates were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) compared with NSR (22.5% and 48.7%, respectively) ( p < 0.001). Undergoing RP was independently associated with decreased cancer-specific mortality (CSM) ( p < 0.01). RP resulted in decreased CSM independent of metastatic stage. Factors associated with increased CSM in patients undergoing RP included T4 stage, highgrade disease, prostate-specific antigen 20 ng/ml, age 70 yr, and pelvic lymphadenopathy ( p < 0.05). Data from the Munich Cancer Registry (MCR) reproduced these findings. Between 1998 and 2010, 1538 patients were newly diagnosed with M+-PCa in the catchment area of the MCR (with 4.6 million inhabitants). Although 1464 patients (95%) did not undergo surgery (RP ), 74 patients (5%) underwent RP (RP+). When evaluating survival in both groups, patients in the RP+ group showed a 55% 5-yr OS rate compared with 21% in the RP group ( p < 0.01) (Fig. 1a and 1b). These data suggest a reproducible, significant survival benefit for patients undergoing RP in patients with newly diagnosed M+-PCa; however, several limitations need to be discussed. In both studies, no data were available on performance status, comorbidity, site-specific externalbeam radiation therapy, and timing and dosage of chemotherapy and androgen deprivation therapy. In addition, no information regarding the extent of bone metastasis was provided, indicating that healthier patients with lower metastatic burden could have been selected and therefore could account for the observed survival benefit. The most important point, however, is that 3–5% have been compared with 95%, and 3–5% ‘‘highly selected’’ patients cannot justify the benefit of extraperitoneal RP in the metastatic situation. Most recently, results from the Zometa European Study (ZEUS) were presented. The investigators evaluated whether zoledronic acid can prevent bone metastases in high-risk M0-PCa patients [5]. At 59 mo, no differences in bone metastases were detected in the zoledronic acid group and the control group. However, patients who underwent RP developed fewer bone metastases, implying that the resection of the primary tumor removed the source of further bone metastases.
In summary, some cohort studies show a benefit of maximal cytoreductive treatment in patients with M+-PCa. However, we would like to emphasize that RP in this patient cohort is considered experimental therapy and ideally should be applied in the context of a clinical trial. Currently, a phase 2 randomized trial of best systemic therapy or best systemic therapy plus definitive treatment of the primary tumor (radiation or surgery) in M+-PCa is enrolling in the United States (http://clinicaltrials.gov/show/NCT01751438). The primary end point of the study will be progression-free survival. A very similar study is being planned in Europe. These studies are needed to explore the potential of RP for M+-PCa patients. Conflicts of interest: The authors have nothing to disclose.
References [1] Esquivel J, Sticca R, Sugarbaker P, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology. Ann Surg Oncol 2007;14:128–33. [2] Polcher M, Zivanovic O, Chi DS. Cytoreductive surgery for advanced ovarian cancer. Womens Health (Lond Engl) 2014;10:179–90. [3] Crispen PL, Blute ML. Role of cytoreductive nephrectomy in the era of targeted therapy for renal cell carcinoma. Curr Urol Rep 2012; 13:38–46. [4] Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol 2014;65: 1058–66. [5] Wirth M, EAU 2013, Oral Presentation, Souvenir Session. Christian Gratzkea,* Jutta Engelb Christian G. Stief a a
Department of Urology, Ludwig-Maximilians-University Munich, Munich, Germany b
Munich Cancer Registry, Munich, Germany
*Corresponding author. Department of Urology, Ludwig-Maximilians-University Munich, Campus Großhadern, Marchioninistr. 15, 81377 Munich, Germany. Tel. +49 89 7095 0; Fax: +49 89 7095 8890. E-mail address: [email protected] (C. Gratzke). April 16, 2014
Please cite this article in press as: Gratzke C, et al. Role of Radical Prostatectomy in Metastatic Prostate Cancer: Data from the Munich Cancer Registry. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.04.009
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Letter to the Editor NOT referring to a recent journal article Role of Radical Prostatectomy in Metastatic Prostate Cancer: Data from the Munich Cancer Registry In several oncologic entities such as ovarian cancer, colon cancer, and renal cell carcinoma, maximal tumor burden reduction, including resection of the primary tumor, results in a survival benefit and an increased response to systemic
therapy [1–3]. Previously, new data have suggested a survival benefit for radical prostatectomy (RP) in metastatic prostate cancer (M+-PCa) patients. Data from the United States (Surveillance Epidemiology and End Results database) were recently published analyzing the outcomes of men with M+-PCa undergoing RP versus no surgery or radiation therapy (NSR) [4]. Of 8185
Fig. 1 – Survival of patients in the Munich Cancer Registry who did and did not undergo radical prostatectomy: (a) patient cohort, 1998–2010; (b) overall survival in M1 prostate cancer patients. ADT = androgen deprivation therapy; RP = radical prostatectomy; RPE = extraperitoneal radical prostatectomy; XRT = external-beam radiation therapy.
http://dx.doi.org/10.1016/j.eururo.2014.04.009 0302-2838/# 2014 Published by Elsevier B.V. on behalf of European Association of Urology.
Please cite this article in press as: Gratzke C, et al. Role of Radical Prostatectomy in Metastatic Prostate Cancer: Data from the Munich Cancer Registry. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.04.009
EURURO-5625; No. of Pages 2 2
EUROPEAN UROLOGY XXX (2014) XXX–XXX
patients, 7811 (95%) received NSR, whereas 245 (3%) underwent RP. The 5-yr overall survival (OS) and predicted disease-specific survival (DSS) rates were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) compared with NSR (22.5% and 48.7%, respectively) ( p < 0.001). Undergoing RP was independently associated with decreased cancer-specific mortality (CSM) ( p < 0.01). RP resulted in decreased CSM independent of metastatic stage. Factors associated with increased CSM in patients undergoing RP included T4 stage, highgrade disease, prostate-specific antigen 20 ng/ml, age 70 yr, and pelvic lymphadenopathy ( p < 0.05). Data from the Munich Cancer Registry (MCR) reproduced these findings. Between 1998 and 2010, 1538 patients were newly diagnosed with M+-PCa in the catchment area of the MCR (with 4.6 million inhabitants). Although 1464 patients (95%) did not undergo surgery (RP ), 74 patients (5%) underwent RP (RP+). When evaluating survival in both groups, patients in the RP+ group showed a 55% 5-yr OS rate compared with 21% in the RP group ( p < 0.01) (Fig. 1a and 1b). These data suggest a reproducible, significant survival benefit for patients undergoing RP in patients with newly diagnosed M+-PCa; however, several limitations need to be discussed. In both studies, no data were available on performance status, comorbidity, site-specific externalbeam radiation therapy, and timing and dosage of chemotherapy and androgen deprivation therapy. In addition, no information regarding the extent of bone metastasis was provided, indicating that healthier patients with lower metastatic burden could have been selected and therefore could account for the observed survival benefit. The most important point, however, is that 3–5% have been compared with 95%, and 3–5% ‘‘highly selected’’ patients cannot justify the benefit of extraperitoneal RP in the metastatic situation. Most recently, results from the Zometa European Study (ZEUS) were presented. The investigators evaluated whether zoledronic acid can prevent bone metastases in high-risk M0-PCa patients [5]. At 59 mo, no differences in bone metastases were detected in the zoledronic acid group and the control group. However, patients who underwent RP developed fewer bone metastases, implying that the resection of the primary tumor removed the source of further bone metastases.
In summary, some cohort studies show a benefit of maximal cytoreductive treatment in patients with M+-PCa. However, we would like to emphasize that RP in this patient cohort is considered experimental therapy and ideally should be applied in the context of a clinical trial. Currently, a phase 2 randomized trial of best systemic therapy or best systemic therapy plus definitive treatment of the primary tumor (radiation or surgery) in M+-PCa is enrolling in the United States (http://clinicaltrials.gov/show/NCT01751438). The primary end point of the study will be progression-free survival. A very similar study is being planned in Europe. These studies are needed to explore the potential of RP for M+-PCa patients. Conflicts of interest: The authors have nothing to disclose.
References [1] Esquivel J, Sticca R, Sugarbaker P, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology. Ann Surg Oncol 2007;14:128–33. [2] Polcher M, Zivanovic O, Chi DS. Cytoreductive surgery for advanced ovarian cancer. Womens Health (Lond Engl) 2014;10:179–90. [3] Crispen PL, Blute ML. Role of cytoreductive nephrectomy in the era of targeted therapy for renal cell carcinoma. Curr Urol Rep 2012; 13:38–46. [4] Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol 2014;65: 1058–66. [5] Wirth M, EAU 2013, Oral Presentation, Souvenir Session. Christian Gratzkea,* Jutta Engelb Christian G. Stief a a
Department of Urology, Ludwig-Maximilians-University Munich, Munich, Germany b
Munich Cancer Registry, Munich, Germany
*Corresponding author. Department of Urology, Ludwig-Maximilians-University Munich, Campus Großhadern, Marchioninistr. 15, 81377 Munich, Germany. Tel. +49 89 7095 0; Fax: +49 89 7095 8890. E-mail address: [email protected] (C. Gratzke). April 16, 2014
Please cite this article in press as: Gratzke C, et al. Role of Radical Prostatectomy in Metastatic Prostate Cancer: Data from the Munich Cancer Registry. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.04.009
