Salvage Radical Prostatectomy in Nonmetastatic Castration

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EUROPEAN UROLOGY 65 (2014) 254–262

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Salvage Radical Prostatectomy in Nonmetastatic Major complications were rectal injury requiring tem- Castration-resistant Prostate Cancer Patients Who porary colostomy in one patient and rectourethral fistula Received Previous Radiotherapy: A Feasibility Study eventually needing pelvic exenteration plus terminal colostomy in another patient. Urinary continence was Nonmetastatic castration-resistant prostate cancer (NM- achieved in seven patients, one remained heavily inconti- CRPC) refers to a rising prostate-specific antigen (PSA) level nent, and four required some sort of urinary diversion under androgen-deprivation therapy (ADT), with testoster- (bilateral nephrostomy and indwelling catheter, each in one one <50 ng/ml in the absence of clinically detectable patient, and two ileal conduits). metastatic disease. It is mostly the result of widespread off- Our preliminary results show that sRP is feasible for label use of primary or salvage ADT in patients with PSA NM-CRPC patients, with an expected complication rate that progression in the absence of metastases. The natural may be higher than that reported for sRP in hormone-naı¨ve history of this disease suggests that only 30% of cases will PCa [4]. This is likely to reflect the more aggressive nature of develop bone metastases and 20% will die within 2 yr [1].At present, no treatment option outside the setting of a clinical trial is recommended for NM-CRPC [2], making the management of this clinical entity a therapeutic challenge. Table 1 – Patient characteristics at baseline (preradiotherapy) and at the time of nonmetastatic castration-resistant prostate cancer We assessed the role of salvage radical prostatectomy (presurgery) (sRP) and extended lymphadenectomy in a prospective feasibility study of 12 patients with NM-CRPC following Characteristic Result primary radiotherapy. The study was approved by the ethics PSA at diagnosis of primary PCa, ng/ml, medial (IQR) 12.4 (4.9–131) committee of the San Giovanni Battista Hospital in Torino, Initial (biopsy) Gleason score Italy, on April 20, 2009. Castration-resistant prostate cancer 76 83 (PCa) was defined as PSA >2 ng/ml of the nadir value [3]. 93 Evidence of bone metastases and/or retroperitoneal disease PSA at salvage RP, ng/ml, median (IQR) 6.3 (3.0–8.8) at bone scan, computed tomography (CT), or positron Age at salvage RP, yr, median (range) 66.5 (54–73) emission tomography (PET)-CT and a PSA density velocity Time to NM-CRPC, mo, median (range) 49 (2–104) Extent of pelvic LND <6 mo represented exclusion criteria. Local failure was Limited LND 1 defined by digital rectal examination, PET-CT, or biopsy. Extended LND 9 Patient characteristics are detailed in Table 1. Retroperitoneal LND 1 At baseline, five patients had intermediate-risk PCa and No LND possible 1 No. of nodes removed, median (range) 21 (0–52) seven had high-risk PCa. Median time from primary No. of positive nodes, median (range) 3 (0–46) treatment to the development of NM-CRPC was 49 mo pT Stage (range: 2–104 mo). Median PSA at salvage surgery was pT2 1 pT3a 3 6.3 ng/ml (interquartile range: 3.0–8.8 ng/ml). On patho- pT3b 6 logic specimen, 11 patients had pT3/pT4 disease, 7 had pT4 2 positive margins, and 6 were pN1. Moreover, 10 patients pN Stage had Gleason score 9 (n =8)or10(n = 2) after sRP. ADT was pN0 5 pN1 6 stopped postoperatively in 10 of 12 patients. PSA nadir pNx 1 <0.2 ng/ml was achieved in six patients. At a median follow- Final Gleason score up of 40.5 mo, 3 of 12 patients had no evidence of disease, 1 72 showed biochemical failure only, 2 developed metastatic 98 10 2 disease, and 6 died of disease. Comparative Kaplan-Meier curves failed to show a significant difference in cancer- IQR = interquartile range; LND = lymph node dissection; NM-CRPC = specific survival for patients who achieved the PSA nadir nonmetastatic castration-resistant prostate cancer; PCa = prostate cancer; PSA = prostate-speciﬁc antigen; RP = radical prostatectomy. and those who did not.

hormone-refractory disease, as documented by the high Paolo[TD$FIRSNAME] [TD$FIRSNAME.]Gontero[TD$SURNAME] a,* proportion of locally advanced or node-metastatic disease Martin[TD$FIRSNAME] [TD$FIRSNAME.]Spahn[TD$SURNAME] b c and Gleason score 9–10 on pathologic specimen. SRP may Giansilvio[TD$FIRSNAME] [TD$FIRSNAME.]Marchioro[TD$SURNAME] [TD$FIRSNAME] d positively affect the natural history of the disease in some Jeffrey R. Karnes Alberto[TD$FIRSNAME] [TD$FIRSNAME.]Briganti[TD$SURNAME] e patients, as shown by the initial PSA response in one of two Bruno[TD$FIRSNAME] [TD$FIRSNAME.]Frea[TD$SURNAME] a cases and by disease-free status in one of four patients. Umberto[TD$FIRSNAME] [TD$FIRSNAME.]Ricardi[TD$SURNAME] f Selection criteria, mainly PSA kinetics cut-off points [1], are Hendrik[TD$FIRSNAME] [TD$FIRSNAME.]van[TD$SURNAME] Poppelg mandatory to identify the subgroup of patients who are Steven[TD$FIRSNAME] [TD$FIRSNAME.]Joniau[TD$SURNAME] g more likely to benefit from surgery for an otherwise lethal disease such as NM-CRPC. aUrology Unit, Department of Surgical Sciences, University of Studies of Torino, Italy bDepartment of Urology, University Hospital Bern, Conflicts of interest: The authors have nothing to disclose. Inselspital, Bern, Switzerland cDepartment of Urology, University of Piemonte Orientale, Novara, Italy dDepartment of Urology, Mayo Medical School and Mayo Clinic, References Rochester, MN, USA eDepartment of Urology, Vita Salute University, [1] Smith MR, Kabbinavar F, Saad F, et al. Natural history of rising serum San Raffaele Scientific Institute, Milan, Italy prostate-specific antigen in men with castrate nonmetastatic pros- fRadiotherapy Unit, Department of Oncology, tate cancer. J Clin Oncol 2005;23:2918–25. University of Studies of Torino, Italy [2] Mottet N, Bellmunt J, Bolla M, et al. EAU guidelines on prostate gUrology, University Hospitals Leuven, cancer. Part II: treatment of advanced, relapsing, and castration- Department of Development and Regeneration, KU Leuven, Belgium resistant prostate cancer. Eur Urol 2011;59:572–83. [3] Roach III M, Hanks G, Thames Jr H, et al. Defining biochemical failure *Corresponding author. University of Studies of Torino, following radiotherapy with or without hormonal therapy in men Department of Surgical Sciences, C.so Dogliotti, 14, Torino, 10126, Italy. with clinically localized prostate cancer: recommendations of the Tel. +39 347 86 00 447; Fax: +390116335581. RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol E-mail address: [email protected] (P. Gontero). Phys 2006;65:965–74. [4] Chade DC, Eastham J, Graefen M, et al. Cancer control and functional August 19, 2013 outcomes of salvage radical prostatectomy for radiation-recurrent Published online ahead of print on August 28, 2013 prostate cancer: a systematic review of the literature. Eur Urol 2012;61:961–71. http://dx.doi.org/10.1016/j.eururo.2013.08.050

in the body is more favorable than choline: The uptake of The New Promise of FACBC Position Emission FACBC in the kidney is negligible, and no activity is found in Tomography/Computed Tomography in the Localization the urinary tract. Other advantages of FACBC are the short of Disease Relapse After Radical Treatment for Prostate synthesis time and a long half-life, which eliminate the Cancer: Are We Turning to the Right Radiotracer? need for an onsite cyclotron, rendering the technique more available. Above all, the first clinical studies showed very The biochemical relapse (BCR) of prostate cancer (PCa) after promising and reproducible results. Improvement in the radical treatment precedes the clinical disease by many detection rate is about 20–30% in comparison with other years, but localizing the site of recurrence is a challenge. imaging techniques, making FACBC the possible radiotracer Positron emission tomography/computed tomography of the future for PCa [4,5]. (PET/CT) with 11C- or 18F-choline is the most accurate In a recent paper published in the European Journal of technique in the assessment of PCa relapse [1], and it can Nuclear Medicine and Molecular Imaging, our group com- detect the site of disease recurrence even with a very low pared FACBC PET/CT with 11C-choline PET/CT in 15 patients prostate-specific antigen (PSA) level [2]. Unfortunately, with BCR after radical prostatectomy and without androgen choline PET/CT can detect only half of the PCa lesions deprivation therapy (mean PSA level at time of enrollment: because of the slow proliferation of PCa cells that reflects a 2.1 Æ 2 ng/ml) [5]. We found better detection rates with slow membrane metabolism with a resulting small amount FACBC for patient analysis (40% vs 20%) as well as lesion of choline uptake [3]. For this reason, some metastatic analysis. In particular, every lesion detected with 11C-choline deposits >10 mm may be negative at choline PET/CT scan. was also visualized with FACBC, but FACBC found twice as Fortunately, research in the field of molecular imaging many positive patients and positive lesions than 11C-choline never stops, and new radiotracers are now under evalua- in the bones, lymph nodes, and prostatic fossa, indicating that tion. In recent years, a synthetic L-leucine analog (anti-1- FACBC may be superior to 11C-choline for the identification of amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC]) PCa cells. Last but not least, the images obtained with FACBC has been proposed as a possible radiotracer for PCa [4]. FACBC were dramatically more clear and evident than those obtained uptake is related to the functional activity of two different with 11C-choline, with a superior target-to-background ratio amino acid transporters, and the distribution of the tracer for FACBC in all lesions. We confirmed our results in a series of