Laparoscopy and Robotics Salvage Laparoscopic Radical Prostatectomy Following High-intensity Focused Ultrasound for Treatment of Prostate Cancer Costantino Leonardo, Giorgio Franco, Cosimo De Nunzio, Andrea Tubaro, Mariarita Salvitti, Nicola Tartaglia, Giovanni Simonelli, and Carlo De Dominicis OBJECTIVE METHODS
To test the feasibility and safety of salvage laparoscopic radical prostatectomy (sLRP) for recurrent prostate cancer after high-intensity focused ultrasound (HIFU) treatment. Thirteen men (median age 61.3 years) fulfilled the criteria of recurrent prostate cancer after HIFU undergoing sLRP with HIFU performed using Ablatherm devices (EDAP TMS, Lyon, France). The median interval from primary treatment and biochemical recurrence was 38 months, and the median serum PSA nadir after primary therapy was 1.05 ng\mL. Perioperative data and functional outcome were recorded for each patient. Complications were recorded and graded according to Clavien scale. The prostatectomy specimens were analyzed for Gleason score, extracapsular extension, and surgical margins. Mean follow-up was 14 months. There was no perioperative mortality and no conversion to open surgery was necessary. Mean operation time was 220 minutes, mean blood loss was 150 mL, and none of the patients received any transfusion. On histopathologic evaluation, 8 patients had extracapsular extension (pT3a) and 5 patients had intracapsular disease (pT2b). Positive surgical margins (PSMs) were detected in 2 patients in the pT3a group. Gleason score was 7 (3 ⫹ 4) in 6 patients and (4 ⫹ 3) in 5 patients. Two patients had a Gleason score of 8. The median time to achieve continence was 6 months. Four patients showed mild incontinence and used 2 pads per day. None of the patients in our series were potent after sLRP. sLRP is feasible for men in whom HIFU has failed but has a higher morbidity rate than primary surgery. UROLOGY 80: 130 –133, 2012. © 2012 Elsevier Inc.
rostate cancer is the most commonly diagnosed non–skin cancer in most developed countries. In Europe, approximately 2.6 million new cases of cancer are diagnosed each year, and prostate cancer constitutes approximately 11% of all male cancer.1 Furthermore, with diagnosis in younger men and the occurrence of stage migration, there has been a shift toward minimally invasive treatments, with potentially reduced morbidity compared with traditional radical therapies. High-intensity focused ultrasound (HIFU) has emerged as one such option. In the development of whole-gland treatments, various nomenclatures have emerged for minimally invasive focal prostate cancer therapies, such as lesiontargeted therapy, hemiablative therapy, or subtotal gland therapy. In Europe and other parts of the world, HIFU has been practiced as a whole-gland modality.1,2 Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, “La Sapienza” University of Rome, Italy Reprint requests: Costantino Leonardo, M.D., Ph.D., Department of Urology, “La Sapienza” University of Rome, Italy. E-mail: [email protected]
com Submitted: January 25, 2012, accepted (with revisions): April 6, 2012
© 2012 Elsevier Inc. All Rights Reserved
According to EAU guidelines, HIFU is categorized as an experimental local treatment of prostate cancer. Most recurrent or persistent prostate cancer after failed HIFU is discovered in the early stages because of the wide use of prostate-specific antigen (PSA) as a marker for monitoring treatment response.2 In the primary cancer setting, it has been shown that laparoscopic radical prostatectomy (LRP) is safe and has equivalent functional and oncologic outcomes to open radical prostatectomy (ORP).3 Salvage ORP (sORP) after primary treatment is well documented with increased operative length and morbidity.4-6 Few series have assessed the early morbidity and efficacy of LRP in the salvage setting after HIFU treatment.1 The primary aim of the current study was to test the feasibility and safety of salvage LRP (sLRP) for recurrent prostate cancer after HIFU treatment.
MATERIALS AND METHODS After approval from the institutional review board, we retrospectively identified 13 patients in our department who under0090-4295/12/$36.00 http://dx.doi.org/10.1016/j.urology.2012.04.014
Table 1. Perioperative data Median age (y), n (range) Median preoperative PSA, ng/mL (range) Median operating time (min), n (range) Median estimated blood loss (mL), n (range) Transfusion rate Conversion rate Mortality Rectal injuries Anastomosis stenosis Continence rate Potency rate
61.3 (49–64) 3.31 ng\ml (2.15–4.70) 220 (195–270) 150 (70–200) 0 0 0 0 2/13 9/13 0
went sLRP between 2008 and 2010 for biopsy-proven local recurrence after HIFU treatment for localized prostate cancer. Thirteen men with a median age of 61.3 years (range 49-64) fulfilled the criteria of recurrent prostate cancer after HIFU and underwent LRP, with HIFU performed using Ablatherm devices (EDAP TMS, Lyon, France). The median serum PSA before primary treatment was 5.2 ng/ mL. Clinical stage before primary therapy was T1c in 11 patients and T2a in 2 patients. Biopsy Gleason score was 6 (3 ⫹ 3) in 10 patients and 7 (3 ⫹ 4) in 3 patients. The median interval from primary treatment and biochemical recurrence (BCR) was 38 months (range 31-42 months) and the median serum PSA nadir after primary therapy was 1.05 ng/mL (range 0.9-1.4). PSA nadir was defined as the lowest value of PSA at any time during the follow-up period. The Stuttgart definition (nadir ⫹ 1.2 ng/mL) was used to determine biochemical recurrence in all patients.7 In all patients, transrectal-guided biopsies of the prostate were performed to documented recurrent cancer, and prostate sizes were evaluated for a mean of 37 mL (range 31-44). All patients were investigated with computed tomography of the abdomen and pelvis and bone scan to rule out metastatic disease. At the time of surgery, medium serum PSA level was 3.31 ng/mL (range 2.15-4.70). All patients were continent and 8 patients reported normal potency after HIFU treatment. A dedicated informed consent, according to our departmental protocol and the available literature, was signed by all patients before sLRP; patients were particularly informed regarding alternative therapeutic options (androgen deprivation therapy, salvage radiation/brachytherapy, and salvage cryotherapy); the higher risk of intraoperative (bleeding, rectal injuries) and postoperative complications (impotence, urinary fistula, urinary incontinence, bladder neck contracture); and the possible benefits (minimally invasive treatment) related to the laparoscopic approach. Perioperative data (operative time, estimated blood loss, rate of conversion, transfusion rate, and transurethral catheter time) and functional outcome (continence and potency) were recorded for each patient (Table 1). Complications were recorded and graded according to Clavien scale.8 The prostatectomy specimens were analyzed for Gleason score, extracapsular extension, and surgical margins.
Figure 1. Intraoperative picture showing fibrosis and adhesion between rectal wall, Denonvilliers’ fascia, and prostate as a result of HIFU treatment. (Color version available online.) vascular bundles with extended lymphadenectomy. The prostate dissection is similar to the open descending approach: bladder neck dissection, freeing of the seminal vesicles, transsectioning of the prostatic pedicles with a LigaSure device (Covidien, Boulder, CO),9 and finally apical dissection. A Van Velthoven anastomosis were performed with 2/0 Monocryl UR6 needle sutures.10 The procedure followed the same steps of the standard LRP according to the technique proposed by Vallancien et al.11 However, because of obliterated tissue planes, tissue ischemia, and adhesions, the procedure was more technically demanding. Adhesions were encountered in all procedures and the presence of the fibrosis made the procedure more demanding, especially during the dissection of the prostate from the muscle elevator, and in particular to the rectal wall (Fig. 1). To avoid rectal injury, the dissection was made closely to the prostate and with digital rectal examination guidance. After a period of 7 days, a plain cystography was performed to rule out leakage of the anastomosis. PSA recurrence after sLRP was defined as a serum level of 0.2 ng/mL or higher. Mean follow-up was 14 months.
RESULTS Perioperative Data and Complications There was no perioperative mortality and no conversion to open surgery was necessary. Mean operation time was 220 minutes (range 195-270) and mean blood loss was 150 mL (range 70-200); none of the patients received any transfusion. Three patients had an anastomotic leak (Clavien Id) and were treated by extended Foley catheterization until day 21. One patient had a trocar wound infection (Clavien grade II) and was treated with antibiotics. Anastomotic stricture developed in 2 patients (Clavien IIIa) at 3 months and was treated by internal urethrotomy. Mean hospital stay was 8 days (range 5-10).
Surgical Technique Transperitoneal LRP was performed in all patients. All cases were performed by 2 experienced surgeons. LRP was performed in non-nerve-sparing fashion taking tissue wide of the neuroUROLOGY 80 (1), 2012
Oncologic Outcomes On histopathologic evaluation, 8 patients had extracapsular extension (pT3a) and 5 patients had intracapsular 131
Table 2. Oncologic and complication outcomes Patient
Post-sLRP Gleason Score
Lymph Nodes Positive
Complication Clavien Scale
1 2 3 4 5 6 7 8 9 10 11 12 13
pT2b pT2b PT3a PT3a PT3a PT3a PT3a pT2b PT3a pT2b pT2b PT3a PT3a
3⫹4 4⫹3 3⫹4 4⫹3 4⫹4 3⫹4 4⫹3 3⫹4 4⫹3 3⫹4 3⫹4 4⫹3 4⫹4
0 0 Yes 0 Yes 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 Yes 0 0 0 0 0 0 0 0
Id 0 0 II 0 Id 0 IIIa IIIa 0 0 0 Id
disease (pT2b). Positive surgical margins (PSMs) were detected in 2 patients in the pT3a group. Gleason score was 7 (3 ⫹ 4) in 6 patients and (4 ⫹ 3) in 5 patients. Two patients had a Gleason score of 8 (Table 2). No patient showed evidence of lymph node metastasis. With regard to oncologic outcome, 1 patient’s PSA at 10 months showed relapse after sLRP and hormonal therapy was started. Functional Outcomes Nine patients were continent, defined as using 0 pads per day. The median time to achieve continence was 6 months. Four patients showed mild incontinence using 2 pads per day but they refused further treatment. None of the patients in our series was potent after sLRP.
COMMENT Most cases of prostate cancer are diagnosed in an early stage. Thus, although active surveillance has increased as a management option for low-risk PC, clinicians are still striving for a middle ground with a modality that has minimal morbidity but definitively gains oncologic control.1 Ablative interventions, such as HIFU, has emerged as a primary treatment option for localized PC, and considerable numbers of patients are being offered this treatment although the EAU guidelines describe HIFU as experimental and the technology is not yet approved by the U.S. Food and Drug Administration. A recent literature review reported that a PSA nadir of ⬍0.5 ng/mL may be achieved in 55-84% of patients. These modalities remain under evaluation and treatment failures are to be expected. Patients who had biochemical failure after HIFU can be managed safely with sLRP, although different nonsurgical salvage options, including repeat HIFU, salvage radiotherapy, brachytherapy, or salvage cryotherapy have been proposed and explored as possible treatments.12,13 However, at this time most of the available evidence is based on small series with limited follow-up and there is no consensus on the standard 132
surgical or nonsurgical treatment in patients who failed HIFU as primary treatment. Further studies with longer follow-up are needed to solve these questions. sLRP remains an option in selected men in whom primary HIFU fails.1-3 To our knowledge there are few publications about sLRP and sORP after HIFU treatment, and more publications on sLRP after radiation therapy.1-3,11,14,15 The widespread use of androgen deprivation therapy in this setting may be the result of the concern of high morbidity related to oSRP, even though consistent evidence shows that ADT cannot be considered a curative treatment. Surgical complications are certainly a matter of concern; however, studies have suggested that oSRP is a safe procedure and has shown acceptable functional outcomes. In addition, to date, results and oncologic control after salvage surgery for HIFU has almost no data and one must appreciate data from salvage RP after radiotherapy. The largest series for sLRP after radiation therapy has been reported by Numez-Mora et al13 and Ahallal et al,3 with 9 and 11 patients, respectively. Both series showed no major complications and only one rectal injury. Numez-Mora et al reported BCR-free rates of 71%, 89%, and 55.5% at 11, 12, and 27 months, respectively. Ahallal et al reported 11 of 15 patients as BCR-free at 8-month follow-up. Lawrentschuk et al published their series of 15 patients treated by sORP after HIFU failure. They reported 1 rectal injury that was repaired with colostomy and a BCR-free in 12 of 14 men with a mean follow-up of 12 months.2 Our series confirmed that sLRP is a feasible and safe minimally invasive procedure. There were no perioperative or postoperative major complications and no deaths; there were 2 readmissions as a result of urethrovesical stenosis. sLRP is more technically demanding for the presence of adhesion, especially a desmoplastic reaction between rectum and prostate. To avoid rectal injury, we followed UROLOGY 80 (1), 2012
the Vallencien et al technique—the so-called “fingerassisted laparoscopy”—and we stayed close to the prostate.11 We found sLRP to result in urinary control comparable with that seen in other series. The rate of urinary incontinence ranges from 10-73% in the open procedure (sORP), whereas in sLRP it oscillates between 22% and 67%, with an incontinence rate in our series of 4 in 13. Our PSM rate (2 of 13 patients) and our BCR-free (12 of 13 patients) rate are attractive but the small sample size and short follow-up prevent us from making any definitive conclusions. Comparing our data with a consecutive series of patients who underwent standard LRP for curative treatment (data not shown), in our experience sLRP was associated with a longer operative time, increased intraoperative bleeding, a longer hospital stay, and a longer time to achieve postoperative urinary continence. Our experience confirmed sLRP as a feasible operation, although it is associated with an increased risk of intra- and postoperative complications when compared with the standard LRP technique.
CONCLUSIONS Our study is a retrospective observation of a small series of patients with short follow-up; however, sLRP is feasible for men in whom HIFU has failed, but it has a higher morbidity than primary surgery References 1. Stolzenburg JU, Bynens B, Do M, et al. Salvage laparoscopic extraperitoneal radical prostatectomy after failed high-intensity focused ultrasound and radiotherapy for localized prostate cancer. Urology. 2007;70(5):956-960. 2. Lawrentschuk N, Finelli A, Van der Kwast TH, et al. Salvage radical prostatectomy following primary high intensity focused ul-
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trasound for treatment of prostate cancer. J Urol. 2011; 185(3):862-868. Ahallal Y, Shariat SF, Chade DC, et al. Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer. BJU Int. 2011;108(5):724-728. Chade DC, Shariat SF, Cronin AM, et al. Salvage radical prostatectomy for Radiation-recurrent prostate cancer: A multi-institutional collaboration. Eur Urol. 2011;60(2):205-210. Stephenson AJ, Scardino PT, Bianco FJ Jr, et al. Morbidity and functional outcomes of salvage radical prostatectomy for locally recurrent prostate cancer after radiation therapy. J Urol. 2004; 172(6 Pt. 1):2239-2243. Leonardo C, Simone G, Papalia R, et al. Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy. Int J Urol. 2009;16(6):584-586. Blana A, Brown SC, Chaussy C, et al. High-intensity focused ultrasound for prostate cancer: comparative defi nitions of biochemical failure. BJU Int. 2009;104:1058-1062. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-213. Leonardo C, Guaglianone S, De Carli P, et al. Laparoscopic nephrectomy using Ligasure system: preliminary experience. J Endourol. 2005;19(8):976-978. Van Velthoven RF, Ahlering TE, Peltier A, et al. Technique for laparoscopic running urethrovesical anastomosis:the single knot method. Urology. 2003;61(4):699-702. Vallancien G, Gupta R, Cathelineau X, et al. Initial results of salvage laparoscopic radical prostatectomy after radiation failure. J Urol. 2003;170(5):1838-1840. Riviere J, Bernhard JC, Robert G, et al. Salvage radiotherapy after high-intensity focussed ultrasound for recurrent localised prostate cancer. Eur Urol. 2010;58(4):567-573. Poissonnier L, Chapelon JY, Rouvière O, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51(2): 381-387. Nuñez-Mora C, García-Mediero JM, Cabrera-Castillo PM. Radical laparoscopic salvage prostatectomy: medium-term functional and oncological results. J Endourol. 2009;23(8):1301-1305. Liatsikos E, Bynens B, Rabenalt R, et al. Treatment of patients after failed high intensity focused ultrasound and radiotherapy for localized prostate cancer: salvage laparoscopic extraperitoneal radical prostatectomy. J Endourol. 2008;22(10):2295-2298.