751 IMPACT OF ADJUVANT RADIOTHERAPY IN PATIENTS WITH PT3A PROSTATE CANCER: SURGICAL MARGINS COUNT

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Salvage therapy in prostate cancer recurrences. Treatment outcome and toxicity after salvage prostatectomy, salvage cryosurgery or 125-I implantation: A multi-centre experience from the Netherlands

Impact on health related quality of life of retropubic radical prostatectomy, external beam radiotherapy, and brachytherapy as treatment of prostate cancer: Results at 3 years follow-up of a prospective, longitudinal and multi-institutional study

Moman M.R.1, Broers E.2, Van Der Poel H.G.3, Vergunst H.2, De Jong I.J.4, Vijverberg P.5, Joshi N.3, Van Vulpen M.1, Battermann J.1, Horenblas S.3

Suarez Novo J.F.1, Aguiló F.1, Ferrer M.2, Guedea F.3, Fernández P.1, Craven-Bratle J.1, Herruzo I.4, Hervás A.5, Macías V.1, Mariño A.6, Ortiz M.J.1, Villavicencio H.7, Franco E.1, Spanish study group on Health Related Quality of Life in prostate cancer

1 Umcu, Dept. of Radiotherapy, Utrecht, The Netherlands, 2Cwz-Hospital, Dept. of Urology, Nijmegen, The Netherlands, 3Netherlands Cancer Institute, Dept. of Urology, Amsterdam, The Netherlands, 4Umcg, Dept. of Urology, Groningen, The Netherlands, 5 St. Antonius Hospital, Dept. of Urology, Nieuwegein, The Netherlands

Hospital Universitari De Bellvitge, Dept. of Urology, Hospitalet De Llobregat, Spain, 2Institut Municipal d’Investigació Mèdica, Dept. of Health Sciences, Barcelona, Spain, 3Institut Català d’Oncologia, Dept. of Radiotherapy, Barcelona, Spain, 4Hospital Regional Carlos Haya, Dept. of Radiotherapy, Málaga, Spain, 5 Hospital Ramón y Cajal, Dept. of Radiotherapy, Madrid, Spain, 6Centro Oncológica de Galicia, Dept. of Radiotherapy, La Coruña, Spain, 7Fundación Puigvert, Dept. of Urology, Barcelona, Spain 1

Introduction & Objectives: Salvage treatments of recurrent tumour after radiation therapy consist of surgery, cryotherapy or brachytherapy. In general practice, toxicity of salvage treatments is considered severe and therefore not commonly performed. Only few studies with a limited number of patients have been published on the outcome and toxicity of salvage treatments. The purpose of this study is to describe Freedom From biochemical Failure (FFF) and toxicity data of patients that received salvage treatment in five clinics in the Netherlands.

Introduction & Objectives: An important migration to less aggressive and lower risk prostate cancer has been observed in patient’s diagnosed last decade due the wide use of PSA. This fact brings an increasing interest on minimal invasive treatments for prostate cancer. Then, with similar outcomes in cancer control at medium time follow-up, the impact on health related quality of life has increased its interest on treatment decision issue. The objective of this study is to compare the effectiveness of Radical Retropubic Prostatectomy (PR), External Beam Radiotherapy (EBRT), and Prostate Brachytherapy (BP), in terms of Quality of Life (QoL), in patients with clinically localized prostate cancer.

Material & Methods: From 1993 to 2008, 116 patients underwent a salvage treatment: Prostatectomy (n = 44), cryosurgery (n = 43) or Iodine-125 (125-I) brachytherapy (n = 29). Data were evaluated retrospectively. Biochemical failure was recorded by using different failure definitions, depending on the method of salvage. Toxicity was scored according to the Common Toxicity Criteria for Adverse Events version 3.0. (CTCAE v3.0).

Material & Methods: Longitudinal observational prospective study. The patients were recruited consecutively at the 10 Spanish clinical centers participating in the study. Patients and physicians made decision on treatment jointly. Inclusion criteria: 1. Low-risk and intermediate-risk prostate cancer, and 2. No previous transurethral resection of the prostate. Pre-treatment and post-treatment evaluations: Months 1, 3, 6, 12, 24, and 36. Clinical variables: TNM, PSA and Gleason. Quality of Life evaluation gathered centrally using computed-assisted telephone administration: SF-36 generic questionnaire. Expanded Prostate Cancer Index Composite (EPIC). Functional Assessment of Cancer Therapy (FACT-G & FACT-P). International Prostate Symptom Score (IPSS). International Index of Erectile Function (IIEF).

Results: For all patients and salvage treatments together the 5-years FFF was 28%. Especially patients with a PSA>10 ng/ml or a PSA doubling time <10 months prior to salvage had a poor outcome (Log Rank test p=0.021 and p=0.003 respectively). As there were significant differences between patient and tumour characteristics in the different groups a comparison between salvage methods regarding outcome could not be performed. For the three salvage modalities, the incidence of grade GU 3 toxicity ranged from 7 to 24% and GI grade 3 from 0 to 9% of patients. There was no grade 4 toxicity. Conclusions: Both biochemical failure and GU toxicity rates are considerable following salvage prostatectomy, salvage 125-I implantation and salvage cryosurgery. Patients showing high-risk disease characteristics should be informed adequately about the low chances of success. Treatment results could be improved if salvage therapy is considered very early in the disease process.



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Impact of adjuvant radiotherapy in patients with pt3a prostate cancer: Surgical margins count Da Pozzo L.F., Gallina A., Suardi N., Briganti A., Bianchi M., Passoni N., Salonia A., Bertini R., Rigatti P., Montorsi F. Vita-Salute University San Raffaele, Dept. of Urology, Milan, Italy Introduction & Objectives: Previous prospective randomized trials have shown a positive impact of adjuvant radiotherapy (RT) in patients with pathologically advanced prostate cancer in terms of biochemical recurrence and clinical recurrence free survival rates. In this context, a major benefit has been shown for patients with positive surgical margins. The aim of this study was to evaluate the impact of adjuvant RT in patients with pathological T3a (pT3a) prostate cancer according to surgical margins (SM) status. Material & Methods: The study included 248 consecutive patients with pT3a prostate cancer treated with radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) at a single European centre between January 1991 and June 2006. Of these, 142 (57.2%) received adjuvant RT, while the remaining 106 (42.8%) did not receive any adjuvant therapy according to surgeon’s preference. The impact of adjuvant RT on biochemical recurrence (BCR) free survival was tested in the overall patient population as well as in patients with positive (+SM) and negative (-SM) surgical margins. The Kaplan Meier method was used to graphically explore BCR free survival rates at 5, 8 and 10 years after surgery in the overall population as well as in +SM and -SM groups, respectively. The log-rank test was used to compare the clinical outcome of patients treated with adjuvant RT vs. no adjuvant RT according to surgical margin status.

Results: A total of 711 patients were initially included, of them 72 rejected keep on the study and 85 were loose due to logistic problems. Then 614 remain useful for the study, 132 RP, 204 EBRT, and 278 BP. At three years follow-up, there are not significant differences among the groups in SF-36 mental domain, but the radiotherapy group has significant worse score than both RP and BP groups in SF-36 physical domain. There are not differences among groups in EPIC urinary domain, but RP has worse scores in urinary/incontinence subdomain, compared with both EBRT and BP, whereas RP has significant better scores in urinary/irritative-obstructive subdomain. In sexual domain RP has significant lower scores than both EBRT and BP. EBRT has worse scores than the others treatments in the intestinal domain. Conclusions: Compared to surgery, both EBRT and BP have significant less impact on sexual function. There are not differences among treatments regarding to urinary domain, but RP has more negative impact in incontinence whereas both EBRT and BP have worse results in irritative/obstructive symptoms. EBRT has significant more negative impact in intestinal function than both RP and BP. Longer follow-up is needed to assess that these results are consistent along the time.



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Adjuvant radiotherapy has no impact on biochemical recurrence free survival in prostate cancer patients with seminal vesicles invasion treated with radical prostatectomy Briganti A.1, Budaeus L.2, Chun F.K.H.2, Gallina A.1, Heinzer H.2, Capitanio U.1, Haese A.2, Suardi N.1, Steuber T.2, Rigatti P.1, Graefen M.2, Karakiewicz P.I.3, Huland H.2, Montorsi F.1 1 Vita-Salute University San Raffaele, Dept. of Urology, Milan, Italy, 2University of Hamburg, Dept. of Urology, Hamburg, Germany, 3University of Montreal, Cancer Prognostics and Health Outcome Unit, Montreal, Canada

Introduction & Objectives: The aim of this study was to test the role of adjuvant RT in a large number of patients with seminal vesicle invasion (SVI) treated with radical prostatectomy (RP) at two large European institutions. Material & Methods: The study included 674 patients with SVI treated with RP at two European tertiary referral centres between November 1989 and July 2008. Since the outcome of the analysis was represented by biochemical recurrence (BCR)-free survival, patients treated with adjuvant HT (n=217, 32.2%) or with unknown adjuvant HT (n=192) were excluded from the analyses. This resulted in 265 patients available for the analyses. Kaplan-Meier analyses were used to evaluate BCR-free survival rates at 2,5 and 8 years after surgery. Univariable and multivariable Coxregression models addressed BCR-free survival, in order to assess the impact of RT on patients outcome, after adjusting for pre-operative PSA, surgical margins status, pathological Gleason sum and presence of lymph node invasion (LNI).

Results: Mean age at surgery was 65.7 yrs (median 66.3 yrs; range: 46-79 yrs). Mean PSA was 15 ng/ml (median 8.9 ng/ml; range 0.6- 93 ng/ml). Pathological Gleason sum was ≤6 in 81 (32.6%), 7 in 125 (50.4%) and 8-10 in 42 (17%) patients, respectively. Overall, 61 patients (24.6%) had lymph node invasion (LNI). Of 142 patients receiving adjuvant RT, 81 (57%) were +SM while the remaining 61 (43%) were -SM. Mean follow-up was 87 months (median 81; range: 24-201). Patients who received adjuvant RT did not differ in terms of PSA, pathological Gleason score distribution and length of follow-up compared to patients not receiving adjuvant RT (all p>0.06). Overall BCR free survival rates at 8,10 and 12 years after surgery were 80,76 and 69%, respectively. Patients treated with adjuvant RT had significantly higher BCR-free survival rates at 8,10 and 12 years after surgery compared to patients not receiving adjuvant RT (88,86 and 81% vs. 70, 64 and 55%, respectively; p=0.004). However, when patients were stratified according to SM status, adjuvant RT was significantly associated with higher BCR free-survival rates only in patients with +SM (p=0.001) and not in patients with -SM (p=0.15).

Results: Mean patient age was 64.5 years (range:44.8-82.3). Median pre-operative PSA was 9.52 ng/ml (mean: 15.78). Pathological Gleason sum was ≤6 in 20 (7.5%), 7 in 199 (75.1%) and 8-10 in 46 (17.4%) of patients. Adjuvant RT was delivered to 126 patients (47.5%). Mean follow-up in BCR-free patients was 48.6 months (median: 41.5; range; 1-226). The 3- and 5-year BCR-free survival rates were 83.5 and 72.0%, respectively. Patients receiving adjuvant RT were not different from patients not receiving adjuvant RT in terms of PSA (p=0.33) and LNI rate (p=0.77), while borderline significant difference in pathologic Gleason sum was observed (p=0.04) between the two groups. The Kaplan-Meier analyses demonstrated no difference in BCR-free survival rates between patients treated and non-treated with adjuvant RT at 2,5 and 8 years after surgery (83, 60, 34% vs. 86,60,26%; log-rank p=0.8). Univariable Cox-regression analysis showed no value of adjuvant RT in predicting BCR (p=0.8). At multivariable analyses, RP Gleason (p=0.02) and lymph node invasion (HR=2.36, p=0.002) represented independent predictors of BCR. Conversely, adjuvant radiotherapy (HR=1.11, p=0.67) was on an independent predictors of BCR.

Conclusions: Adjuvant RT is effective in preventing BCR after RP and ePLND in patients with pT3a +SM prostate cancer. However patients with -SM did not benefit from adjuvant RT. Therefore, patients with pT3a +SM seem to be excellent candidates for a multimodal combined approach.

Conclusions: Patients with SVI treated with RP with or without adjuvant RT showed high rates of biochemical recurrence. Among them, pathologic Gleason sum and the presence of lymph node invasion represent independent predictors of BCR. Our data demonstrate that the delivery of adjuvant radiation therapy alone does not affect BCR-free survival.

Eur Urol Suppl 2009;8(4):308