Prostate Int xxx (2016) 1e4 Contents lists available at ScienceDirect Prostate International journal homepage: http://p-international.org. Original Article Cytoreductive surgery for men with metastatic prostate cancer * Nikolas Katelaris 1, Declan Murphy 2, 3, Nathan Lawrentschuk 1, 2, 3, 4, , Athos Katelaris 5, Daniel Moon 2, 3 1 University of Melbourne, Department of Surgery, Austin Hospital, Melbourne, Australia 2 University of Melbourne, Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia 3 Epworth Healthcare, Melbourne, Australia 4 Olivia Newton-John Cancer Research Institute, Austin Hospital, Melbourne, Australia 5 St. Georges, University of London, London, United Kingdom article info abstract Article history: Background: Cytoreductive surgery for metastatic prostate cancer is an emerging area of interest with a Received 24 September 2015 potentialupside that includes local control, delayed initiation of hormone therapy, and possibly improved Accepted 12 November 2015 cancer specific survival. In order for radical prostatectomy to be an effective treatment option for men in Available online xxx this group, the benefits must outweigh the surgical morbidity. The aim of this study was to present a case series and assess the literature feasibility of cytoreductive surgery for men with metastatic prostate Keywords: cancer. Cytoreduction Methods: The case series (n ¼ 6) evaluated each patient with regard to preoperative prostate-specific Metastasis Prostatectomy antigen, grade, stage, adjuvant therapy, and surgical outcomes. A full literature review of cytoreductive Prostatic neoplasms radical prostatectomy was undertaken. Results: A surgical approach had demonstrated benefit without deleterious effect in these case. Notably, in the three men on ADT pre-operatively, the PSA remained lower after aggressive treatment of local and metastatic disease, and at follow-up, none of the men had local symptoms from malignancy or the surgery. Conclusions: This case series supports recent data demonstrating that radical prostatectomy for care- fully selected men is feasible. There is a need for further studies to explore the role of cytoreductive surgery in men with oligometastatic prostate cancer. © 2016 Asian Pacific Prostate Society, Published by Elsevier. All rights reserved. 1. Introduction going studies to assess the outcomes for men undergoing radical surgery in the presence of oligometastatic prostate cancer. Aggressive cytoreductive surgery for men with metastatic Men included in this series had oligometastatic PC and were prostate cancer (PC) is not yet a part of mainstream urology and is offered cytoreductive surgery after careful discussion with the considered by some to be experimental1; however, there is growing treating physician. Outcome was measured by surgical complica- evidence to support radical prostatectomy (RP) for selected men tions and postoperative continence recovery. The cases were un- with oligometastatic disease. The potential benefits include pre- dertaken in Melbourne, Australia, between 2012 and 2014. The vention of local complications and improved cancer-specific sur- series consisted of five men who underwent robot-assisted radical vival.2,3 A combined treatment approach incorporating RP and prostatectomy (RARP) and one pelvic exenteration for PC. Their stereotactic radiation can delay the initiation of hormone therapy presenting features are outlined in Table 1, and the surgical and or possibly avoid it altogether. This treatment approach is still in the oncological outcomes are summarized in Table 2. exploratory phase, and there is a need for further data from on- 2. Case series * Corresponding author. University of Melbourne, Department of Surgery, Patients 1e3 presented with solitary bony metastases and Austin Hospital, Burgundy St, Melbourne 3084, Australia. Tel.: þ61 3 9455 3363; fax: þ61 3 9387 1000. Gleason 9 malignancy on biopsy. Patient 6 presented with two sites E-mail address: [email protected] (N. Lawrentschuk). of osseous metastases in addition to a single lymph node metastasis http://dx.doi.org/10.1016/j.prnil.2015.11.003 p2287-8882 e2287-903X/© 2016 Asian Pacific Prostate Society, Published by Elsevier. All rights reserved. Please cite this article in press as: Katelaris N, et al., Cytoreductive surgery for men with metastatic prostate cancer, Prostate Int (2016), http:// dx.doi.org/10.1016/j.prnil.2015.11.003 2 Prostate Int xxx (2016) 1e4 Table 1 Summary of Patientsepresenting Features Patient Age Initial PSA Gleason Clinical stage Sites of metastasis Time from Pre-operative ADT Local symptoms Cytoreductive (yr) (ng/mL) score diagnosis surgery to surgery 1 77 7.8 4þ5 T2b 7th rib 4 wk eeRARP 2 65 30.0 4þ5 T2b Right inferior pubic ramus 11 mo LHRH agonist Obstructive voiding RARP symptoms 3 69 27.0 5þ4 T3b L3 vertebra 4 wk eeRARP 4 49 62.0 4þ4 T2b T11 vertebra 5 yr LHRH agonist e RARP 5 68 81.0 4þ3T4 4th rib, T7 vertebral body 9 yr LHRH agonist þ bicalutamide Haematuria, bladder Pelvic outlet & ureteric exenteration obstruction 6 55 45.0 4þ4 Not known Symphysis pubis, right inferior 5 mo LHRH agonist e RARP pubic ramus, & left internal iliac node ADT, androgen-deprivation therapy; LHRH, luteinizing hormone-releasing hormone; PSA, prostate-specific antigen; RARP, robot-assisted radical prostatectomy. and Gleason 8 disease on biopsy. These patients were otherwise fit voiding, but no sign of metastatic progression on restaging. Given and well and expressed a strong preference for local treatment, the profound symptomatology related to the locally invasive pelvic accepting that: (1) this was not mainstream management; (2) malignancy, he elected for cystoprostatectomy/anterior resection. oncologic outcomes could not be easily predicted; and (3) that they Patients 1e4 and 6 had an uncomplicated recovery from RARP, could subsequently receive stereotactic radiation to the bony le- with a median hospital stay of 2 days (1e3). All regained continence sions. Patients 2 and 4 proceeded under the auspice of a clinical within 3 months and remained pad-free at follow-up. Patient 5 trial involving the treatment of men with oligometastatic disease. required temporary colonic diversion for a rectal anastomotic leak, Patients 4 and 5 had been diagnosed years earlier and denied and subsequently recovered well. All patients proceeded to addi- local treatment due to the presence of metastatic disease at pre- tional treatment to sites of metastatic disease with a variable PSA sentation. Patient 4 underwent RARP after his prostate-specific response, however, at follow-up, three of the six men required antigen (PSA) had remained stable for 5 years on androgen- recommencement of ADT for biochemical progression. Notably, in deprivation therapy (ADT). Patient 5 had undergone radiation for the three men on ADT pre-operatively, the PSA remained lower a solitary rib metastasis at presentation 9 years earlier, following after aggressive treatment of local and metastatic disease, and at which ADT was commenced. He was referred with castrate- follow-up, none of the men had local symptoms from malignancy resistant disease and significant local progression causing recur- or the surgery. A surgical approach had demonstrated benefit rent urosepsis, haematuria, ureteric obstruction, and obstructive without deleterious effect in these cases. Table 2 Surgical and Oncologic Outcomes Patient Cytoreductive Surgical Final Pathological Surgical Postoperative Postoperative Postoperative Follow-up Follow-up Follow-up surgery complications Gleason stage margin PSA (ng/mL) ADT radiation (mo.) continence PSA score status (ng/mL) 1 RARP þ pelvic e 4þ5 pT3bN1 Negative 1.23 e Stereotactic 8 Pad-free 0.36 lymphadenectomy radiation to 7th rib 2 RARP e 4þ5 pT3bNx Negative 0.77 LHRH Stereotactic 21 Pad-free 0.44 agonist þ radiation to bicalutamide pubic ramus (POPSTAR trial) 3 RARPþ pelvic e 5þ4 pT3bN0 Focal positive 19.9 LHRH Stereotactic 21 Pad-free 4.7 lymphadenectomy margins at agonist þ radiation to L3 base, apex bicalutamide vertebra 4 RARP þ pelvic e 4þ5 pT3bN0 Positive <0.1 LHRH agonist Adjuvant 36 Pad-free 0.1 lymphadenectomy radiotherapy, subsequent stereotactic radiation to right iliac lesion (POPSTAR trial) 5 Pelvic exenteration Colorectal 4þ3 pT4N0 N/A 0.3 Nil Stereotactic 10 Ileal conduit 5.1 anastomotic leak radiation to managed with new metastatic defunctioning lesions 7 mo. stoma Post-op (pelvic lymph node, ilium, rib) 6 RARP Nil 4þ4 pT2c Negative <0.01 LHRH agonist Stereotactic 17 Pad-free 0.07 (ceased 2 mo. radiation to post- RARP) three metastatic sites ADT, androgen-deprivation therapy; LHRH, luteinizing hormone-releasing hormone; N/A, not applicable; PSA, prostate-specific antigen; RARP, robot-assisted radical prostatectomy. Please cite this article in press as: Katelaris N, et al., Cytoreductive surgery for men with metastatic prostate cancer, Prostate Int (2016), http:// dx.doi.org/10.1016/j.prnil.2015.11.003 Katelaris et al / Cytoreductive surgery for men 3 3. Discussion operative staging modality13,14 superseding CT and nuclear- medicine bone scans. The rapid introduction of PSMA PET scan- Locally advanced PC is a highly morbid condition. The compli- ning into clinical practice means there are a growing number of cations of uncontrolled pelvic malignancy include recurrent men who are being classified as having M1 disease, because it is bladder neck obstruction requiring transurethral resection of the more sensitive than traditional imaging techniques. It is, therefore, prostate, gross haematuria