Does the extent of positive margins influence on biochemical recurrence after radical prostatectomy?
Long-term oncological outcomes of laparoscopic radical prostatectomy
Alvarez M.1, De La Morena J.M.1, Martín D.2, Amaruch N.1, Hernández V.1, Sánchez M.1, Carrera C.1, Llorente C.1
Hruza M., Flinsbach B., Stock C., Teber D., Rassweiler J.
Hospital Universitario Fundación Alcorcón, Dept. of Urology, Madrid, Spain, 2Hospital Universitario Fundación Alcorcón, Dept. of Preventive Medicine, Madrid, Spain
Introduction & Objectives: Although the presence of positive surgical margins (PSM) after radical prostatectomy (RP) is a well known risk factor for biochemical recurrence (BR), the extent of the margin is not a predictive factor in most studies. Nevertheless, it seems logical that a larger tumor burden on the margin site could expose patients to a higher risk of BR. We evaluate the role of the extent of PSM on PSA recurrence in our patients. Material & Methods: Prospective cohort study that included patients who underwent RP from 19992006. No adjuvant treatments were used. All specimen were sectioned at 3 mm intervals with sagital sections in apex and bladder neck. Sections were entirely embedded and studied microscopically by a single pathologist. Tumor volume was assessed based on the size and number of sections affected. PSM were measured in millimetres. BR was considered with a value exceeding 0.4 ng/ ml. The following variables were gathered: age, clinical tumour stage, preoperative PSA, Gleason score, D´Amico´s risk classification, pT stage, prostate and tumor volume, site and extent of PSM and postoperative PSA. The qualitative variables are presented by frequency distribution and the quantitative variables by the mean (SD) and median (IQR). Median BR times and BR rates at 1, 2, 3 years after the radical prostatectomy (RP) were estimated using Kaplan-Meier methods. Hazard ratios and 95% CIs were calculated with Cox´s proportional hazards regression model. Results: 403 patients with a median follow up of 39.3 months (18 – 66) were included. Mean age was 63.7 (5.7) years. Median preoperative PSA value was 6.3 (4.8-6.8) ng/ml. Median tumor volume was 2.1 (0.8 – 5.6) cc. Median length of margins was 6 mm (3 – 12). Overall percentage of PSM was 36%, with a significant drop-out in time to 13.6% in last year. Univariate analysis showed a statistically significant association between BR and clinical stage (p<0.0001), D´Amico´s risk classification (p<0.0001), pT (p<0.0001), Gleason score (p<0.0001) and PSM (p<0.0001). Among the patients with BR, 26.3% had a length of PSM longer than 6 mm compared to only 9.8 % of those who had a length shorter than 6 mm (p<0.02) At 1, 2 and 3 years, BR-free rates were, respectively, 99.5% (EE 0.3), 97.9 % (0.7) and 96.6 % (1) . At median follow-up this percentage was 92.9% in patients with BR and 99.5% of those without PSA relapse (p < 0.0001) . Multiple Cox regression model showed that the principal factors associated with a BR were the presence of PSM (HR 3.01, CI 95% 1.5 – 5.9), Gleason score (HR 1.4, CI 95% 1.1-1.9) and D´Amico´s risk classification (HR 3.9 CI 95% 1.5-10.2).
Slk-Kliniken, Dept. of Urology, Heilbronn, Germany Introduction & Objectives: In our clinic, laparoscopic radical prostatectomy (LRP) has been performed in daily clinical practice for 10 years now. As one of the first institutions we are able to present long-term follow-up data of our first patients. Material & Methods: 370 of our first 500 patients (74.0%) were available for longterm follow-up of at least 6 years. Median follow-up was 89 months (range 74-115). 120 of them even had a follow-up of more than 8 years. 59.7% were staged pT2, 21.4% pT3a and 18.9% pT3b/pT4. Survival was calculated using Kaplan-Meier methods. Results: Overall survival was 94.9% at 5 years and 93.2% at the end of the followup. 8 patients died from prostatic cancer, 17 died from other causes: Myocardial infarction (4 patients), plasmocytoma, pancreatic malignoma, aneurysm of a cerebral arteria, carcinoma of the liver (2 patients), carcinoma of the rectum, stroke (2 patients), malignoma of the oesophagus, brain tumor, cardiac death, transitional cell carcinoma of the urinary bladder, renal cell carcinoma. Therefore, Prostatecancer specific survival was 98.6% at 5 years and 97.8% at the end of the follow-up. The 8 patients who died from progression of prostatic cancer had pT3aGleason8, pT3aGleason9, pT3bGleason7, pT3bGleason9 and pT4Gleason9 tumors. At 24 months after surgery, the PSA elevation-free survival was 97.7%, 88.0% and 85.9% for pT2-, pT3a- and pT3b/pT4-tumors respectively. At 60 months it was 88.3%, 68.0% and 60.9%, at 96 months it was 85.9%, 60.9% and 49.8% for the 3 groups mentioned above. Disease-free survival defined as absence of local or distant recurrence of the prostatic carcinoma at 24 months was 100.0% in pT2-, 94.7% in pT3a and 95.3% in pT3b/pT4-tumors. At 60 months, 97.7%, 88.0% and 78.1% disease-free survival were calculated for the 3 groups, at 96 months 97.2%, 84.4% and 78.1% of the patients were free of recurrence.
Conclusions: Based on this study, the length of PSM is not a prognostic factor for PSA relapse and should, therefore, not necessarily be included in the final report for radical prostatectomy specimens. The main prognostic factors were the presence of PSM, Gleason score and a preoperative high risk tumor.
Conclusions: Our data shows a low prostate-cancer specific morbidity after LRP. Within the follow-up, no patient with localised prostate cancer died from progression of the disease. PSA elevation-free survival and disease-free survival were significantly higher in patients with pT2-tumors compared to pT3a- and pT3b/pT4-tumors.
Which are the patients at risk to recur beyond 10 years after radical prostatectomy? Suardi N.1, Briganti A.1, Gallina A.1, Da Pozzo L.F.1, Tutolo M.1, Bianchi M.1, Passoni N.1, Capitanio U.1, Karakiewicz P.I.2, Rigatti P.1, Montorsi F.1 Vita-Salute University San Raffaele, Dept. of Urology, Milan, Italy, University of Montreal, Cancer Prognostics and Health Outcomes Unit, Montreal, Canada 1
Introduction & Objectives: Overall, up to 40% of patients undergoing radical prostatectomy (RP) will demonstrate biochemical recurrence (BCR). However, only few studies reported the long term recurrence rates of patients treated with RP. We examined the rate of BCR which occurred after 10 years of recurrence free survival and aimed at identifying patients at risk of late recurrence. Material & Methods: Between January 1988 and June 2008, 4574 consecutive patients were treated with radical prostatectomy (RP) at a single European tertiary referral centre. Of these, 280 had available BCR-free survival beyond 10 years of follow-up. Patients had complete pathological data including pathological stage and Gleason sum. Kaplan-Meier curves explored the time to BCR starting from the 10 year-follow-up. Moreover, univariable and multivariable Cox regression analyses were fitted to assess the factors associated with late BCR. Covariates consisted of pathological stage, namely pT2, extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node invasion (LNI), surgical margins status (SM), as well as pathological Gleason sum. Results: Mean follow-up was 152 months (median: 144.5 ; range: 121260). Pathological stage was pT2, ECE, SVI and LNI in 106 (37.8%), 52 (18.6%), 38 (13.6%) and 51 (18.2%) patients, respectively. Pathological Gleason sum was 2-6, 7 and 8-10 in 200 (71.4%), 60 (21.4%) and 20 (7.2%) patients, respectively. Positive SMs were found in 56 patients (20%). Of all 280 patients, 38 had late BCR (13.6%). BCR free survival rates at 2 and 5 years after the 10-year landmark were 87 and 79%, respectively (Figure 1). At univariable and multivariable Cox regression models the presence of SVI was the only significant predictors of late BCR (all p≤0.007). Conclusions: Our data show that a non-negligible proportion of patients are at risk of developing BCR beyond the 10-year landmark. Patients with SVI seem to be at higher risk of late BCR. Whether this late recurrences represent clinically meaningful events still needs to be demonstrated.
Eur Urol Suppl 2009;8(4):278
Impact of age and comorbidity on oncologic outcome and continence following laparoscopic radical prostatectomy Vallancien G., Prapotnich D., Mombet A., Cathala N., Rozet F., Barret E., Cathelineau X. Institut Montsouris, Paris Descartes University, Dept. of Urology, Paris, France Introduction & Objectives: Surgery is uncommon in senior adults (70+ years) with localized prostate cancer1. This is attributed to an increased risk of postoperative incontinence and the belief that men will not die of their prostate cancer. We assessed the influence of age and comorbidity on continence, PSA relapse and mortality following laparoscopic radical prostatectomy. Material & Methods: 2048 consecutive men underwent laparoscopic radical prostatectomy for localized prostate cancer in a single center between January 2002 and April 2006. Comorbidity was assessed using the Charlson index which rates 19 major comorbidies according to their severity (0=no major comorbidity; Maximum=37)2. Patient’s characteristics, pathological stage, continence, PSA relapse and mortality were analysed by age and Charlson classes. Continence was analysed after a minimum of 12-month follow-up. Results: Of the 2048 men, 297 were aged ≥70 years and 281 had a charlson index >0 (diabetes 31%, chronic pulmonary disease 26%, prior other non metastatic cancer 16%, prior myocardial infarction 12%, gastric ulcerative disease 8%). Pathological stage significantly increased with age and to a lesser extend with comorbidity. Postoperative continence significantly declined with age but was not influenced by comorbidity. Over a mean follow-up of 4.4 years, 31 patients (1.5%) died (prostate cancer 1.1%; other cause 0.4%), with no significant difference between age and comorbidity classes. Age 70+ (n=297) 9.3 56.3 25.6
Charlson score 1 2+ (n=185) (n=98) 7.8 8.9 54.2 56.4 25.7 26.1
10.2 60.6 25.5
7.8 59.4 26.1
0.08 0.03 0.004
12% 20% 40.5% 26.5% 1% 20%
11% 21.5% 37% 30% 0.5% 22%
12% 18% 43% 26.5% 0.5% 21%
12% 26% 36% 25% 1% 18%
7% 22% 42% 29% 0% 18%
42% 52% 6% 4.4
33% 57% 10% 5.0
41% 52% 7% 4.3
43% 50% 7% 5.0
45% 50% 5% 5.0
25.7% 1.3% 0.6%
30.3% 1.7% 0%
0.046 0.114 0.29
25.1% 0.9% 0.5%
30.3% 2.2% 0.5%
22.4% 2% 0%
0.25 0.25 0.65
78% 6% 16% 1%
67.5% 10% 21% 1.5%
80% 6% 13% 1%
74% 10% 16% 0%
79% 6% 13% 1%
0 (n=1765) <0.001 <0.001 0.04
<60 (n=659) Preoperative PSA*, ng/ml
60-69 (n=1092) 9.1
Prostate weight*, g Body mass index*, kg/m2 Pathological stage - T2a - T2b - T2c - T3-4 - All T, N+ Positive margins
49.1 26.2 13% 16.5% 49% 21% 0.5%
Gleason specimen - <6 -7 - 8+ Follow-up*, years Outcome: - PSA relapse - Death due to PCa - Death due to other cause Postoperative continence - No pad - 1 pad/day - ≥2 pads/day - Artificial sphincter *mean value; **defined by 2 consecutive values of PSA ≥ 0.2ng/ml
46% 48% 6% 4.2 22.8% 0.5% 0.5% 87% 5.5% 7% 0.5%
Conclusions: In our experience, prostate cancer pathological stage increases with age. Laparoscopic radical prostatectomy is feasible in fit senior adults ≥ 70 years, especially those at high risk of unfavorable oncologic outcome. Two out of 3 men will return to normal continence postoperatively. Over a mean follow-up of 5 years, overall survival is very high. Longer term follow-up is needed. 1SEER data for 2000–2004 ( http://www.cancer.gov/); 2Charlson ME et al. J Chronic Dis 1987;40: 373–383.