Survival analysis of patients with biochemical relapse after radical prostatectomy treated with androgen deprivation: Castration-resistance influential factors.

INTRODUCTION: We evaluate the prognosis of patients with biochemical recurrence (BCR) treated with androgen deprivation therapy (ADT) and to determine the influential factors to castration resistance (CR) and death. METHODS: From a series of 1310 patients with T1-T2 prostate cancer treated with radical prostatectomy between 1989 and 2012, 371 had BCR. Patients with lymph node involvement were excluded. We analyzed only the 159 treated with salvage ADT. At the end of the study, 77 (48%) had developed CR. RESULTS: The median follow-up to CR was 9.2 years. The CR-resistant free survival (RFS) was 76 ± 3%, 62 ± 3% and 43 ± 9% in 5, 10 and 15 years, respectively. The RFS median time was 14 years. In the multivariate study, the prostate-specific antigen (PSA) doubling time (PSA-DT) was <6 months (p = 0.01) (hazard ratio [HR] 3; 95% confidence interval [CI] 1.4-6.8, p = 0.007); seminal vesicle involvement (HR 3.1; 95% CI 1.5-6.2, p = 0.01) and PSA velocity in ng/mL/year (HR 1.3; 95% CI 1.1-1.5, p = 0.002) with better cut-off points of 0.84 ng/mL/year (p = 0.04) (HR 4; 95% CI 1.7-9.4, p = 0.001) were influential variables. Specific survival (SS) at 5, 10 and 15 years since surgery was 96 ± 1, 85 ± 2 and 76 ± 4, respectively. The time of CR to death was 30 ± 6% at 5 years, with the median at 3.2 years. In the multivariate only Ki 67 (HR 1.04; 95% CI 1.005-1.08, p = 0.02) had an independent influence. CONCLUSIONS: In BCR patients treated with ADT, the median to CR was 14 years. PSA-DT <6 months, PSA velocity (ng/mL/year) and seminal vesicle involvement were influential variables. From the CR, the median time to death was 3.2 years. Ki-67 marker was an independent influence.

Radical prostatectomy. Detailed surgical margins. Prognostic value of multifocal involvement in pT2 (+).

OBJECTIVES: We intend to analyze the prognostic value of positive surgical margins depending on their number and location in pT2 patients. METHODS: We analyze 448 (34.3%) patients with positive surgical margins from a series of 1,310 T1-T2 patients treated with radical prostatectomy between 1989-2012. Of them 164 are pT2 (+). 119 (72.6% ) have unifocal affectation (41 (34.5%) unifocal in right lobe; 35 (29.4%) unifocal in left lobe, 40 (33.6%) unifocal in apex, 3 (2.5% ) unifocal proximal) and 45 (27.4%) multifocal involvement. RESULTS: Unifocal and multifocal pT2(+)patients have not evidenced significant differences in any of the clinicopathologic variables compared. However the BPFS at 5 and 10 years is significantly worse in the multifocal group, (p<0.000) In the BPFS multivariate study of 164 pT2(+ )influential variables are: multifocal involvement (HR: 3.4; 95%IC 1.7-6.9 p<0.000) and PSA (HR: 1.03; 95%IC 1.02-1.05 p<0.000), being PSA >15 ng/ml )HR: 3.7; 95%IC 2.1-6.6 p<0.000 ( the best cut-off point. Risk groups: Using the independent influence variables, the best model (using Cox models ) includes two risk groups: Group 1 (0 variables): They are pT2(+) with unifocal affectation and PSA<15 ng/ml, (63%). Their BPFS are 81±4% and 77±4% (5 and 10 years). Grupo 2 (1-2 variables): They are pT2 (+) with multifocal involvement, PSA> 15 ng/ml or both of them, (37%). Their BPFS are 46±6% and 26±7% (5 and 10 years). The BPFS differs significantly between the two groups (p<0.000). The Group 1 BPFS is similar to the pT2 (-) patients, (p:0.242). The Group 2 BPFS is similar to the pT3(+) patients, (p:0.637). The model explained significantly better the BPFS than any of the individual variables analyzed. CONCLUSIONS: In pT2(+) patients the prognosis is significantly worse in multifocal involvement. In addition two groups of patients can be clearly distinguished from the BPFS point view according to their influential variables. The data suggest that since the prognostic point view the second group is understaged while the first is overstaged.

Radical prostatectomy. Prognostic value of positive surgical margins in pT2 patients.

OBJECTIVES: We intend to assess the prognostic influence of surgical margins on the biochemical progression free survival (BPFS) in patients classified as pT2 after radical prostatectomy. METHODS: We analyze a series of 1,132 T1-T2 patients with prostate cancer treated with radical prostatectomy between 1989-2009. PT3b, pT4 and patients with lymph node involvement were excluded from the series. The clinicopathologic variables and the BPFS of pT2(+), pT2(-) and pT3 patients are compared. The influential clinicopathologic variables in the BPFS are identified in the pT2(+) group and risk groups are designed. RESULTS: Of 1,051 patients evaluated finally: 598 (59,6) were pT2(-) 163 (15,5%) pT2(+)80 (7,6%) pT3a(-) and 210 (20%) pT3(+). Clinical characteristics of pT2(+). It is homogeneous with the pT2(-) group and significantly better than pT3(+) group in all the clinicopathologic variables evaluated. 5 and 10 year BPFS of the pT2(68 ± 3% and 57 ± 5%) is significantly worse than pT2( -)(87 ± 1% and 79 ± 2%), similar to pT3a(-) (75 ± 5% and 64 ± 7%and better than pT3(+) (44 ± 3% and (36 ± 3%) BPFS pT2(+) influential factors: Univariate study : Pathological Gleason score 7-10 (HR:2.1 95% IC: 1.1-4.1), (p=0.02)MRI that indicates T3 (HR:3.2 95%IC: 1.4-7.3), (p=0.04) PSA > 15 ng-ml (HR:4 95% IC: 2-8.2), (p < 0.0001) and high risk D'Amico group (HR:3.3 95%IC: 1.3-8.5), (p=0.01) are influential variables. A risk model with the involved variables can be designed. Each variable present is a point. Two groups are designed : Group 1 (0-1 variable) Group 2 (2-3 variables). 5 and 10 year BPFS for Group 1 are 71±5% and 69 ± 5%, and are 37 ± 12% and 22 ± 11% for Group 2. (p < 0.0001). CONCLUSIONS: Surgical margins in pT2 patients have independent influence in the BPFS. The group is heterogeneous and it can be divided into two risk groups accordingly to the BPFS influential variables: a larger group (86% pT2(+) with worse prognosis than pT2(-), and a smaller group (remaining 14%) with similar prognosis to pT3 (+).It is likely that pT2(+) patients are a mixture of understaged patients with others with iatrogenic margins or false margins due to poor assessment of the surgical specimen.

[Prostate adenocarcinoma. Predictive clinical model of seminal vesicle involvement]. / Adenocarcinoma de próstata. Modelo clínico predictivo de afectación de vesícula seminal.

OBJECTIVES: Our aim is to design a predictive model of seminal vesicle involvement. using clinical data. METHODS: We studied 1128 patients with clinically localized adenocarcinoma treated by radical prostatectomy (127 were pT3b). We identified (logistic regression) clinical variables related with pT3b. With the multivariate study influential variables a seminal vesicle involvement risk model is designed. RESULTS: Seminal vesicle involvement related factors: In univariate study: the influential variables are: Gleason 7 (OR:2);Gleason 8-10 (OR:4.5) T2 (OR:2.6); bilateral involvement in biopsy (OR:3.1); PSA 10-20 ng/ml ( OR:3.3); PSA >20 ng/ ml (OR:9.5). In the multivariate study are influential: Gleason 7 (OR:1.56) Gleason 8-10 ( OR: 3.4); T2 (OR:1.9); PSA 10-20 ng/ml (OR:3.1) and PSA >20 ng/,ml (OR:8.8). Predictive model: using multivariate logistic regression the weight of each variable is valued and a value between 1 and 4 is given. Gleason 2-6, T1; PSA<10 ng/ml value 1; Gleason 7; T2 y PSA 10-20 ng/ml value 2; Gleason 8-10 and PSA >20 ng/ml value 4. Each patient has a marker that fluctuates between 3 and 10. 5 Groups are designed with significantly different risks (p<0.05 in all cases ): Group 1 (3 points) (OR:1) (risk: 2.4% 95%IC 0.7%-4.3%) Group 2 (4 points) (OR:2.7) (risk: 6.5% 95%IC 5%-7.9%); Group 3(5-6 points) (OR:7.1)( risk:15% 95%IC 11%-19%) Group 4 ( 7--8 points) (OR:33.4) (risk: 45.5%; 95%IC 30%-59%) Group 5 (9-10 points) (OR:57.3) (risk: 58.8% 95%IC 35%- 82%). CONCLUSION: The clinical model allows an accurate approximation to the seminal vesicles involvement risk.

Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment.

PURPOSE: The purpose of this study was to evaluate a dual tracer 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) and (11)C-choline positron emission tomography (PET) protocol in the detection of biochemical prostate cancer relapse. PROCEDURES: Seventy-three patients (median Prostate Specific Antigen (PSA) Test value 2.7 ng/ml (1.1-5.4)) after radical treatment. PET scans were performed by means of a ECAT-Exact HR+ in the first 18 patients and in a PET/computed tomography Biograph II in the remaining 55 patients. RESULTS: The sensitivity of (11)C-choline and FDG was 60.6% and 31%. In PSA levels over 1.9 ng/ml, sensitivity increased to 80% and 40%, respectively. In the group receiving adjuvant hormone therapy, the diagnostic yields were 71.2% and 43%, respectively. While (11)C-choline-PET could not differentiate well and poorly differentiated Gleason score patients, FDG-PET results were almost significant (p = 0.058). CONCLUSIONS: A PSA value higher than 1.9 ng/ml determines a significant increase in the diagnostic yield. Adjuvant hormonotherapy has no influence on the PET results. FDG has a better correlation with the Gleason score than (11)C-choline.

Phase II trial of radiation dose escalation with conformal external beam radiotherapy and high-dose-rate brachytherapy combined with long-term androgen suppression in unfavorable prostate cancer: feasibility report.

PURPOSE: To determine the feasibility of combined long-term luteinizing hormone-releasing hormone agonist-based androgen suppressive therapy (AST) and dose escalation with high-dose-rate (HDR) brachytherapy for high-risk (HRPC) or very-high-risk prostate cancer (VHRPC). METHODS AND MATERIALS: Between January 2001 and October 2006, 134 patients (median age, 70 years) with either National Comprehensive Cancer Network criteria-defined HRPC (n = 47, 35.1%) or VHRPC (n = 87, 64.9%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen level of 14.6 ng/mL, a median clinical stage of T2c, and a median Gleason score of 7. Three-dimensional conformal radiotherapy (54 Gy in 30 fractions) was followed by HDR brachytherapy (19 Gy in 4 b.i.d. treatments). Androgen suppressive therapy started 0-3 months before three-dimensional conformal radiotherapy and continued for 2 years. RESULTS: One implant was repositioned with a new procedure (0.7%). Five patients (3.7%) discontinued AST at a median of 13 months (range, 6-18 months) because of disease progression (n = 1), hot flashes (n = 2), fatigue (n = 1), and impotence (n = 1). After a median follow-up of 37.4 months (range, 24-90 months), the highest Radiation Therapy Oncology Group-defined late urinary toxicities were Grade 0 in 47.8%, Grade 1 in 38.1%, Grade 2 in 7.5%, and Grade 3 in 6.7% of patients. Maximal late gastrointestinal toxicities were Grade 0 in 73.1%, Grade 1 in 16.4%, Grade 2 in 7.5%, and Grade 3 in 2.9% of patients. There were no Grade 4 or 5 events. CONCLUSIONS: Intermediate-term results show that dose escalation with HDR brachytherapy combined with long-term AST is feasible and has a toxicity profile similar to that reported by previous HDR brachytherapy studies.

Treatment of ureteroarterial fistulae with covered vascular endoprostheses and ureteral occlusion.

BACKGROUND: Ureteroarterial fistulae (UAFs) are a rare entity, often difficult to identify, and associated with a high mortality rate. This fact has been attributed to a delay in diagnosis and treatment. Five conditions that can predispose to the development of this uncommon entity have been described: prior pelvic surgery, prolonged ureteral stenting, radiation therapy, previous vascular surgery and vascular pathology. METHODS: We present 4 patients with UAFs and at least three of the above-mentioned conditions. Ureteral ischemia and subsequent necrosis promote the formation of these fistulae. The constant pulsation of the iliac artery is transmitted to an already compromised ureter containing a stiff intraluminal foreign body, resulting in pressure necrosis, most likely where the ureter crosses the iliac artery. RESULTS AND CONCLUSION: Cases were managed percutaneously with a combination of the deployment of a covered prosthesis and, when needed, with mechanical occlusion of the ureter. Hematuria stopped in all the patients with no evidence of immediate rebleeding. One patient presented a new episode of vaginal bleeding 13 months after endograft placement and ureteral embolization. Arteriography showed the presence of a hypogastric artery pseudoaneurysm that was occluded using coils. No new bleeding has occurred in this patient 12 months after the second embolization. At present all 4 patients are alive with follow-up periods of 5, 9, 11 and 25 months since the first procedure.