Radical Prostatectomy in Metastatic Castration-resistant Prostate Cancer: Feasibility, Safety, and Quality of Life Outcomes

Chad A. Reichard; Justin R. Gregg; Mary F. Achim; Ana M. Aparicio; Curtis A. Pettaway; Louis L. Pisters; John F. Ward; John W. Davis; Brian F. Chapin

doi:10.1016/j.eururo.2018.03.031

Radical Prostatectomy in Metastatic Castration-resistant Prostate Cancer: Feasibility, Safety, and Quality of Life Outcomes

Chad A. Reichard, Justin R. Gregg, Mary F. Achim, Ana M. Aparicio, Curtis A. Pettaway, Louis L. Pisters, John F. Ward, John W. Davis, Brian F. Chapin

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Radical prostatectomy (RP) in well selected men with metastatic castration-resistant prostate cancer (mCRPC) is safe with minimal minor complications. RP in mCRPC is discouraged outside of well-designed clinical trials other than for symptom palliation.

Original language	English (US)
Pages (from-to)	140-143
Number of pages	4
Journal	European urology
Volume	74
Issue number	2
DOIs	https://doi.org/10.1016/j.eururo.2018.03.031
State	Published - Aug 2018

Keywords

Castration resistant
Metastatic
Outcomes
Prostate cancer
Prostatectomy
Quality of life

ASJC Scopus subject areas

Urology

Access to Document

10.1016/j.eururo.2018.03.031

Cite this

@article{503ee5b9c80c42e2ac6faaf788e826b2,

title = "Radical Prostatectomy in Metastatic Castration-resistant Prostate Cancer: Feasibility, Safety, and Quality of Life Outcomes",

abstract = "Radical prostatectomy (RP) in well selected men with metastatic castration-resistant prostate cancer (mCRPC) is safe with minimal minor complications. RP in mCRPC is discouraged outside of well-designed clinical trials other than for symptom palliation.",

keywords = "Castration resistant, Metastatic, Outcomes, Prostate cancer, Prostatectomy, Quality of life",

author = "Reichard, {Chad A.} and Gregg, {Justin R.} and Achim, {Mary F.} and Aparicio, {Ana M.} and Pettaway, {Curtis A.} and Pisters, {Louis L.} and Ward, {John F.} and Davis, {John W.} and Chapin, {Brian F.}",

note = "Funding Information: Castration resistant Metastatic Prostate cancer Prostatectomy Outcomes Quality of life Ongoing clinical trials are testing the effect of local therapy in men with de novo metastatic prostate cancer (PCa). Proposed mechanisms of benefit include elimination of the immunosuppressive effect of the primary tumor, removal of a source of lethal clone reseeding and systemic release, and avoidance of local progression morbidity [1] . Signs and symptoms of local progression can decrease patients{\textquoteright} performance status and limit candidacy for systemic therapies, impacting survival. Palliative outlet procedures or urinary diversion may also be required. While these complications reportedly occur in 36–61% of men with de novo metastatic PCa [2] , a large proportion never shows signs or symptoms of local progression. Improved systemic agents might also delay the onset of symptoms from local progression. Thus, local therapy, with its own incumbent toxicities, may be best delayed to later disease stages. The impact of the disease state and exposure to multiple lines of systemic therapy on patients{\textquoteright} ability to undergo local therapy is poorly described, and little is also known regarding the urinary quality of life (QOL) outcomes of radical prostatectomy (RP) in metastatic castration-resistant PCa (mCRPC). Therefore, we endeavored to describe our center's experience with RP in the setting of mCRPC. We identified 14 patients with mCRPC who underwent RP during 2008–2016—eight in the setting of consideration for enrollment in a clinical trial requiring successful primary tumor DNA sequencing and six given clinical judgment and/or extensive local disease burden ( ). Patients who were deemed to have surgically resectable disease by physical examination and/or magnetic resonance imaging underwent RP. Patients met mCRPC criteria if they had radiographically visible lesions on computed tomography or bone scan, and subsequently met Prostate Cancer Working Group 2 Table 1 [3] criteria for castrate-resistant prostate-specific antigen (PSA) progression. Additionally, any patients with symptomatic progression in the absence of PSA progression were included. Complications within 90 d were assigned Clavien-Dindo grade. Pre- and postoperative Expanded Prostate Cancer Index Composite (EPIC) urinary domain QOL outcomes were analyzed [4] . Institutional review board approval to perform this retrospective analysis was obtained. Median patient age was 56 yr (interquartile range [IQR] 50–60; Supplementary Table 1). Median time from the start of first systemic treatment to mCRPC was 6.7 mo (IQR 5.1–10.3) and median time from mCRPC to RP was 5.1 mo (IQR 1.4–12.0; Supplementary Table 2). Five (36%) patients received platinum-based chemotherapy prior to RP for aggressive variant PCa (Supplementary Table 1) per institutional protocol ng/ml), seven patients had an increase in PSA after RP (range 0.1–24.5 ng/ml), and PSA was unchanged in three patients ( ). Detailed progression and survival data are not included in this analysis as the majority of these patients are enrolled in clinical trials and this information will be reported upon trial completion. [5] . Four patients had a decrease in PSA after RP (range 0.2–57.3 Fig. 1 Median operative time was 239 min (IQR 186–304). Median estimated blood loss was 200 cc (IQR 150–225). One patient was transfused postoperatively. Nine of 14 patients underwent bilateral non–nerve-sparing operations. One patient had excision of the trigone with bilateral ureteral reimplants due to concern for gross tumor involvement. Median length of stay was 1.5 d (range 1–6). Positive surgical margin rate was 57%. Twelve of 14 patients had significant residual viable tumor; two of 14 patients had residual viable tumor considered as “single cells” or “cell clusters” only (all by hematoxylin and eosin staining). Median tumor width and length in largest cross-sectional dimension were 3.0 cm (IQR 2.4–3.2) and 2.2 cm (IQR 1.4–2.5), respectively. Seven patients had cribriform architecture and/or intraductal spread, which when present after neoadjuvant therapy has been associated with worse outcome [6] . Three of six cN0 patients were pN1. One of eight cN1 patients was pN0. Thirteen of 14 patients underwent pelvic lymphadenectomy with a median of three (IQR 0–4) positive lymph nodes out of 17 (IQR 11–25) lymph nodes removed. One lymphadenectomy was aborted due to matted lymph nodes. Interestingly, 28.6% of the patients had pathologically node-negative disease. Operative time, blood loss, and length of stay were all qualitatively within the ranges for patients with localized disease. There were no intraoperative complications. There was one postoperative Clavien-Dindo Grade III complication, while four additional patients experienced either Grade I or II complications (Supplementary Table 4). There were no 30-d mortality events, and 12 of 14 patients were alive at 1 yr after RP. The majority of complications were related to bacterial infections, which may or may not reflect an increased baseline risk due to colonization from multiple prior healthcare encounters, given ongoing treatment of advanced disease [7] . Functional outcomes of RP in various stages of advanced PCa have been described with one multi-institutional report of pad-free rates of 57.4% [8] . In patients with CRPC invading the pelvic floor or urethral sphincter, a report of 31 patients describes prostatectomy with bladder neck closure and cutaneous vesicostomy to avoid poor functional outcomes [9] . In our cohort, all patients underwent vesicourethral anastomosis. Median preoperative and <3-mo postoperative EPIC urinary function QOL scores were 84 (IQR 70–95) and 78 (IQR 62–81), respectively. One patient had an increase in early postoperative QOL score, one patient had a clinically insignificant decrease in early postoperative QOL score, and two patients had a significant decrease in American Urological Association symptom score, suggesting potential symptomatic benefit from surgery (Supplementary Table 3). While the median decline in 3mo postoperative QOL scores in our cohort was clinically significant (clinical significance defined as change in score of ≥6) [4] , this magnitude of early decline appears similar to the pattern seen in a large series of patients with localized disease, who then had a subsequent substantial increase back toward baseline at 6–12 mo [10] . Five of nine patients alive at last follow-up had no significant voiding symptoms. No patients died of obstructive uropathy. Limitations include the single-center, retrospective nature of the study. There is a clear selection bias, and the number of patients with mCRPC evaluated for surgery but deemed to have unresectable local disease burden by prostatectomy alone is unknown. We demonstrate that in this selected group of younger patients, RP was feasible with a reasonable safety profile. Given the heterogeneity of this heavily pretreated population, clinical benefit cannot be directly ascribed to the intervention, and thus, we caution against RP in mCRPC outside of well-designed clinical trials other than for symptom palliation. Author contributions: Brian F. Chapin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Reichard, Chapin. Acquisition of data: Achim, Reichard, Chapin. Analysis and interpretation of data: Reichard, Chapin. Drafting of the manuscript: Reichard, Aparicio, Chapin. Critical revision of the manuscript for important intellectual content: Reichard, Gregg, Aparicio, Pettaway, Pisters, Ward, Davis, Chapin. Statistical analysis: Reichard. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Chapin. Other: None. Financial disclosures: Brian F. Chapin certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: John W. Davis—consultant: Intuitive Surgical; research study funding: Janssen, GenomeDx. Funding/Support and role of the sponsor: None. Appendix A ",

year = "2018",

month = aug,

doi = "10.1016/j.eururo.2018.03.031",

language = "English (US)",

volume = "74",

pages = "140--143",

journal = "European urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - Radical Prostatectomy in Metastatic Castration-resistant Prostate Cancer

T2 - Feasibility, Safety, and Quality of Life Outcomes

AU - Reichard, Chad A.

AU - Gregg, Justin R.

AU - Achim, Mary F.

AU - Aparicio, Ana M.

AU - Pettaway, Curtis A.

AU - Pisters, Louis L.

AU - Ward, John F.

AU - Davis, John W.

AU - Chapin, Brian F.

N1 - Funding Information: Castration resistant Metastatic Prostate cancer Prostatectomy Outcomes Quality of life Ongoing clinical trials are testing the effect of local therapy in men with de novo metastatic prostate cancer (PCa). Proposed mechanisms of benefit include elimination of the immunosuppressive effect of the primary tumor, removal of a source of lethal clone reseeding and systemic release, and avoidance of local progression morbidity [1] . Signs and symptoms of local progression can decrease patients’ performance status and limit candidacy for systemic therapies, impacting survival. Palliative outlet procedures or urinary diversion may also be required. While these complications reportedly occur in 36–61% of men with de novo metastatic PCa [2] , a large proportion never shows signs or symptoms of local progression. Improved systemic agents might also delay the onset of symptoms from local progression. Thus, local therapy, with its own incumbent toxicities, may be best delayed to later disease stages. The impact of the disease state and exposure to multiple lines of systemic therapy on patients’ ability to undergo local therapy is poorly described, and little is also known regarding the urinary quality of life (QOL) outcomes of radical prostatectomy (RP) in metastatic castration-resistant PCa (mCRPC). Therefore, we endeavored to describe our center's experience with RP in the setting of mCRPC. We identified 14 patients with mCRPC who underwent RP during 2008–2016—eight in the setting of consideration for enrollment in a clinical trial requiring successful primary tumor DNA sequencing and six given clinical judgment and/or extensive local disease burden ( ). Patients who were deemed to have surgically resectable disease by physical examination and/or magnetic resonance imaging underwent RP. Patients met mCRPC criteria if they had radiographically visible lesions on computed tomography or bone scan, and subsequently met Prostate Cancer Working Group 2 Table 1 [3] criteria for castrate-resistant prostate-specific antigen (PSA) progression. Additionally, any patients with symptomatic progression in the absence of PSA progression were included. Complications within 90 d were assigned Clavien-Dindo grade. Pre- and postoperative Expanded Prostate Cancer Index Composite (EPIC) urinary domain QOL outcomes were analyzed [4] . Institutional review board approval to perform this retrospective analysis was obtained. Median patient age was 56 yr (interquartile range [IQR] 50–60; Supplementary Table 1). Median time from the start of first systemic treatment to mCRPC was 6.7 mo (IQR 5.1–10.3) and median time from mCRPC to RP was 5.1 mo (IQR 1.4–12.0; Supplementary Table 2). Five (36%) patients received platinum-based chemotherapy prior to RP for aggressive variant PCa (Supplementary Table 1) per institutional protocol ng/ml), seven patients had an increase in PSA after RP (range 0.1–24.5 ng/ml), and PSA was unchanged in three patients ( ). Detailed progression and survival data are not included in this analysis as the majority of these patients are enrolled in clinical trials and this information will be reported upon trial completion. [5] . Four patients had a decrease in PSA after RP (range 0.2–57.3 Fig. 1 Median operative time was 239 min (IQR 186–304). Median estimated blood loss was 200 cc (IQR 150–225). One patient was transfused postoperatively. Nine of 14 patients underwent bilateral non–nerve-sparing operations. One patient had excision of the trigone with bilateral ureteral reimplants due to concern for gross tumor involvement. Median length of stay was 1.5 d (range 1–6). Positive surgical margin rate was 57%. Twelve of 14 patients had significant residual viable tumor; two of 14 patients had residual viable tumor considered as “single cells” or “cell clusters” only (all by hematoxylin and eosin staining). Median tumor width and length in largest cross-sectional dimension were 3.0 cm (IQR 2.4–3.2) and 2.2 cm (IQR 1.4–2.5), respectively. Seven patients had cribriform architecture and/or intraductal spread, which when present after neoadjuvant therapy has been associated with worse outcome [6] . Three of six cN0 patients were pN1. One of eight cN1 patients was pN0. Thirteen of 14 patients underwent pelvic lymphadenectomy with a median of three (IQR 0–4) positive lymph nodes out of 17 (IQR 11–25) lymph nodes removed. One lymphadenectomy was aborted due to matted lymph nodes. Interestingly, 28.6% of the patients had pathologically node-negative disease. Operative time, blood loss, and length of stay were all qualitatively within the ranges for patients with localized disease. There were no intraoperative complications. There was one postoperative Clavien-Dindo Grade III complication, while four additional patients experienced either Grade I or II complications (Supplementary Table 4). There were no 30-d mortality events, and 12 of 14 patients were alive at 1 yr after RP. The majority of complications were related to bacterial infections, which may or may not reflect an increased baseline risk due to colonization from multiple prior healthcare encounters, given ongoing treatment of advanced disease [7] . Functional outcomes of RP in various stages of advanced PCa have been described with one multi-institutional report of pad-free rates of 57.4% [8] . In patients with CRPC invading the pelvic floor or urethral sphincter, a report of 31 patients describes prostatectomy with bladder neck closure and cutaneous vesicostomy to avoid poor functional outcomes [9] . In our cohort, all patients underwent vesicourethral anastomosis. Median preoperative and <3-mo postoperative EPIC urinary function QOL scores were 84 (IQR 70–95) and 78 (IQR 62–81), respectively. One patient had an increase in early postoperative QOL score, one patient had a clinically insignificant decrease in early postoperative QOL score, and two patients had a significant decrease in American Urological Association symptom score, suggesting potential symptomatic benefit from surgery (Supplementary Table 3). While the median decline in 3mo postoperative QOL scores in our cohort was clinically significant (clinical significance defined as change in score of ≥6) [4] , this magnitude of early decline appears similar to the pattern seen in a large series of patients with localized disease, who then had a subsequent substantial increase back toward baseline at 6–12 mo [10] . Five of nine patients alive at last follow-up had no significant voiding symptoms. No patients died of obstructive uropathy. Limitations include the single-center, retrospective nature of the study. There is a clear selection bias, and the number of patients with mCRPC evaluated for surgery but deemed to have unresectable local disease burden by prostatectomy alone is unknown. We demonstrate that in this selected group of younger patients, RP was feasible with a reasonable safety profile. Given the heterogeneity of this heavily pretreated population, clinical benefit cannot be directly ascribed to the intervention, and thus, we caution against RP in mCRPC outside of well-designed clinical trials other than for symptom palliation. Author contributions: Brian F. Chapin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Reichard, Chapin. Acquisition of data: Achim, Reichard, Chapin. Analysis and interpretation of data: Reichard, Chapin. Drafting of the manuscript: Reichard, Aparicio, Chapin. Critical revision of the manuscript for important intellectual content: Reichard, Gregg, Aparicio, Pettaway, Pisters, Ward, Davis, Chapin. Statistical analysis: Reichard. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Chapin. Other: None. Financial disclosures: Brian F. Chapin certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: John W. Davis—consultant: Intuitive Surgical; research study funding: Janssen, GenomeDx. Funding/Support and role of the sponsor: None. Appendix A

PY - 2018/8

Y1 - 2018/8

N2 - Radical prostatectomy (RP) in well selected men with metastatic castration-resistant prostate cancer (mCRPC) is safe with minimal minor complications. RP in mCRPC is discouraged outside of well-designed clinical trials other than for symptom palliation.

AB - Radical prostatectomy (RP) in well selected men with metastatic castration-resistant prostate cancer (mCRPC) is safe with minimal minor complications. RP in mCRPC is discouraged outside of well-designed clinical trials other than for symptom palliation.

KW - Castration resistant

KW - Metastatic

KW - Outcomes

KW - Prostate cancer

KW - Prostatectomy

KW - Quality of life

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DO - 10.1016/j.eururo.2018.03.031

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Radical Prostatectomy in Metastatic Castration-resistant Prostate Cancer: Feasibility, Safety, and Quality of Life Outcomes

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Keywords

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