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Purpose: To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy., Methods and Materials: Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03., Results: Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade 3., Conclusions: With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To analyse the rate of secondary malignancies observed in a series of 675 prostate cancer patients who underwent a permanent implant brachytherapy between 1999 and 2003, and to compare the incidence with the expected rate in a matched general French population., Material and Methods: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125-iodine seeds and a prescription dose of 145Gy. The mean follow-up was 132 months., Results: The 10-year overall survival for the entire cohort was 92% (95% confidence interval [CI]: 90-94). The 10-year relapse-free survival rate was 82% (95% CI: 79-85). Overall, 61 second cancers were registered. When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93). For colorectal cancer, the SIR was 0.45 (95% CI: 0.19-0.89). For lung cancer, the SIR was 0.38 (95% CI: 0.17-0.76). The SIR for all cancers was 0.61 (95% CI: 0.47-0.79). When excluding secondary colorectal and lung cancers (both with low SIRs in this series), the SIR for all cancers was 1.06 (95% CI: 0.77-1.29)., Conclusion: With a mean follow-up of more than 11 years, this series does not detect any excess risk of second cancers associated with permanent implant prostate brachytherapy. However, due to power limitation, a small increase in the risk of secondary malignancies cannot be totally ruled out., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Optimal management of locally recurrent prostate cancer after definitive radiation therapy is still challenging. With the development of highly accurate radiotherapy devices, prostate salvage re-irradiation might generate lower toxicity rates than classical salvage therapies. We retrospectively evaluated the toxicity and the feasibility of a prostate re-irradiation after definitive radiation therapy failure. Two modalities were investigated: high-dose-rate brachytherapy (HDRB) on whole prostate gland and focal stereotactic radiotherapy (SBRT) using CyberKnife® linac., Methods: Between 2011 and 2015, 28 patients with imaged and/or biopsy-proven intra-prostatic recurrence of cancer after definitive radiation therapy underwent a salvage re-irradiation using HDRB (n = 10) or focal SBRT (n = 18). The schedule of re-irradiation was 35 Gy in 5 fractions. Biological response (defined as post-salvage radiation PSA variation) and biochemical no-evidence of disease (bNED) were evaluated in the whole cohort. For patients who had a positive biological response after salvage radiation, biochemical recurrence (BCR) and survival after salvage radiotherapy were evaluated. Post-salvage toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and were compared to baseline status., Results: Within a median follow-up of 22.5 months (IQR = 8-42), 9 (90%) patients experienced a positive biological response after salvage HDRB and 5 (50%) remained bNED at the end of the follow-up. Among patients who initially responded to salvage HDRB, the BCR rate was 44.4% after a median interval of 19.5 months (IQR = 11.5-26). Only one patient experienced a transient grade 3 urinary complication. In the SBRT group, the median follow-up was 14.5 months (IQR = 7-23) and 10 (55.6%) out of the 18 patients remained bNED. Among the 15 patients who initially responded to salvage SBRT, 5 (33.3%) experienced a BCR. One patient experienced a transient grade 4 urinary complication. At the end of the follow-up, all evaluated patients had a urinary status grade variation ≤ +1 grade. No grade 3-4 digestive toxicity was observed., Conclusions: Salvage prostate re-irradiation for locally recurrent cancer is feasible and generate low toxicities rates when using with HDRB or focal SBRT. However, further investigations are necessary to confirm these findings and to determine predictive features for patients who might benefit from such an approach.

Purpose: To analyse long-term overall survival, relapse-free survival and late toxicities in a series of 675 patients treated between 1999 and 2003, with a median follow-up of 132 months., Patients and Methods: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125 iodine seeds. Hormone therapy, consisting most often of an anti-androgen alone, was given in 393 patients (58%)., Results: The 10-year overall survival was 92% (95% confidence interval [CI]: 90-94) without a significant difference between the low and the select intermediate-risk groups (P=0.17). The 10-year relapse-free survival rate for the entire cohort was 82% (95% CI: 79-85), and was significantly higher in the low-risk group than in the intermediate one (87 vs 71%; P<0.0001). Twenty-six percent of the relapses observed in this series occurred after more than 10 years of follow-up. The 10-year cumulative incidence of grade 3-4 urinary toxicity (whatever the delay and the recovery) was 5.78%. The cumulative incidence of grades 3-4 rectal toxicity in the present series was 1.65% at 10 years. As for sexual toxicity, 61% of our patients retained an erectile capacity at 10 years (with or without oral medication), with age being a major factor., Conclusion: With a median follow-up of more than 11 years, this series appears to confirm the excellent long-term results of low-dose rate prostate brachytherapy, both in terms of survival and in terms of toxicity., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

With an experience of more than 25 years for the pioneers (and more than 14 years in France), permanent implant brachytherapy using iodine 125 seeds (essentially) is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. The possible extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group has now been confirmed by several studies. Moreover, for the other patients in the intermediate-risk group and for the patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best ways to escalate the dose. Different permanent implant brachytherapy techniques have been proposed; preplanning or real-time procedure, loose or stranded seeds (or both), manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints, which have been recently redefined by the international societies, such as the GEC-ESTRO group. Mid- and long-term results, which are now available in the literature, indicate relapse-free survival rates of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3 to 5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome, which may significantly alter the quality of life of the patients, and last several months. In spite of those drawbacks, with excellent long-term results, low rates of incontinence and impotence, and emerging new indications (focal brachytherapy, salvage brachytherapy after localized failure of an external irradiation), permanent implant prostate brachytherapy can be expected to be proposed to an increasing number of patients in the next future., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To determine whether quantitative dynamic contrast-enhanced MRI improves the performance of T2W-MRI for the localisation of non-palpable prostate cancer (PCa) and for the estimation of tumor volume., Materials and Methods: Twenty-three patients (PSA: 8.91+/-6.2ng/m) with a non-palpable cancer underwent endorectal MRI with T2W and dynamic contrast enhanced (DCE) imaging before radical prostatectomy. Each level of evaluation (apex, mid-portion, base) was divided in eight areas (24 areas per prostate and 552 areas for the 23 patients). Localisation and volume of tumor foci greater than 0,2cc present on the radical prostatectmoy specimens were retrospectively correlated to their MR appearance on the 552 evaluated areas. The dynamic parameters included capillary permeability (K(trans)), maximum concentration of gadolinium after 60s of perfusion ([Gd]) and wash-out (K(ep)). Uni- and multivariate analysis were performed to determine which parameters were predictive of PCa., Results: Mean values of K(trans), K(ep) and [Gd] were significantly higher in the 58 tumor foci greater than 0,2 cm(3) of the PZ and the TZ (all p<0.05). Logistic regression for each zone provides provided a value of the area under the ROC curve of 0.83 for the PZ and 0.81 for the TZ (0.7 and 0.75, respectively, for the T2W imaging), only significant for the PZ (p<0.002). Sensitivity and specificity were 79 and 77% for the PZ, 62.5 and 94% for the TZ. Above 0,2 cm(3), tumor volume on dynamic MR showed a mean difference of 51+/-100% (range: -145 to +248%)., Conclusions: Quantitative dynamic MRI is more accurate than T2W imaging for tumor localisation of non-palpable cancer greater than 0,2 cm(3), but the difference is only significant for the PZ. Above this volume, correlation between tumor volume measured on dynamic MRI and that on the specimen is poor.

With an experience of more than 20 years for the pionneers (and more than 10 years in France), permanent implant brachytherapy using Iodin 125 seeds is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. An extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group is presently under study. Moreover, for patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best way to escalate the dose for some patients. Various permanent implant brachytherapy techniques have been proposed; preplanning or real-time techniques, loose seeds or stranded seeds, manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints which have been recently redefined by the Groupe européen de curiethérapie--European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) group. Mid- and long-term results which are now available in the literature indicate relapse-free survival of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Some comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3-5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome which may be significant and last several months. In spite of those drawbacks, with excellent long-term results and low rates of incontinence and impotence, brachytherapy can be expected to be proposed to an increasing number of patients in France in the next future.

Purpose: The aim of this study was to analyze overall and relapse-free survival in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than American Brachytherapy Society (ABS) criteria., Methods and Materials: Between January 1999 and September 2004, 809 patients were treated with permanent loose 125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809 patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between 10 and 15, or a Gleason score of 7, or both (non-ABS group)., Results: Overall 5-year survival was 98%, with no difference between the ABS group and the non-ABS patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS group; it was significantly lower (p = 0.001) in the non-ABS group but remained satisfactory at 94%. On subgroup analysis, the results appeared to be better for the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason score of 7., Conclusions: Our results suggest that selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed as recipients of permanent implant brachytherapy as monotherapy.

A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.

Purpose: To assess the frequency of the PSA "bouncing" phenomenon after a significant follow-up in a series of patients treated by permanent implant brachytherapy for a prostate cancer. To look for the clinical and dosimetric parameters possibly linked to this transitory secondary PSA increase. To evaluate in which percentage of cases this bouncing could have mimicked a biochemical relapse according to the ASTRO consensus criteria., Patients and Methods: From January 1999, to December 2001, 295 patients were treated by a permanent prostate implantation (real-time technique, with free (125)I seeds- Isoseed Bebig-) by the Institut Curie-Hôpital Cochin-Hôpital Necker Paris group. The mean follow-up is 40.3 months (9-66 months). The PSA level was regularly checked, at least every 6 months. We defined as a "bouncing" all increase in PSA, starting at 0.1 ng/ml, subsequently followed by a spontaneous (without any treatment) decrease, with return to the previous level or lower. We particularly focused on the patients fulfilling the criteria for a biochemical relapse according to the ASTRO consensus (Three successive increases in PSA). A multivariate analysis tried to identify independent factors among the usual clinical and dosimetric parameters., Results: In our series, 161 patients (55%) showed a transitory PSA increase (bouncing) of at least 0.1 ng/ml; 145 patients (49%) a bouncing of 0.2 ng/ml, 93 patients (32%) a bouncing of 0.4 ng/ml and 43 patients (15%) a bouncing of at least 1 ng/ml. Mean PSA bounce was 0.8 ng/ml (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of the total number) presented three successive PSA increases with a significant (3 months) interval between the dosages, and therefore were to be considered as being in biochemical relapse according to the ASTRO consensus criteria. Actually, among those 32 patients, 18 (56%) subsequently showed a complete normalization of their PSA, without any treatment. Ten patients went on increasing their PSA, and were considered to be really in biochemical relapse. For the last 4 patients, the situation still remains ambiguous. In multivariate analysis, age<70 years (P<0.00001) and D90>200 Gy (P<0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml., Conclusions: The observed rate of 32% of patients showing a PSA bouncing of at least 0.4 ng/ml in our series is in good agreement with what has been previously reported in the literature. Age<70 years and D90>200 Gy were found to be independent factors predicting for such a secondary transitory increase in PSA. Interestingly, among 32 patients fulfilling the classical criteria of the ASTRO for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, demonstrating that the ASTRO consensus is not well adapted to the biochemical follow-up of our patients undergoing permanent implant prostate Brachytherapy.

Background: Circulating tumor cells (CTCs) cannot be readily detected with currently available methods in the majority of patients with prostate cancer. Telomerase activation, one of the major immortalization events, is found in most cases of prostate cancer. We attempted to develop a method using telomerase activity to isolate CTCs in patients with prostate cancer., Patients and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using Ficoll-Hypaque. Immunomagnetic beads coated with an epithelial cell-specific antigen antibody (BerEP4) were used to harvest epithelial cells from PBMCs. Telomerase activity was detected in harvested epithelial cells using the telomerase-PCR-enzyme-linked immunosorbent assay method., Results: Blood samples from 107 patients with prostate cancer were studied. CTCs were detected in 19 of 24 (79%) patients with advanced prostate cancer. In contrast, CTCs were not detected in blood samples from 22 healthy male volunteers. CTCs were even identified in patients with an undetectable (<0.1 ng/ml) serum prostate-specific antigen (PSA). CTCs were detected in 55 of 70 (79%) patients with localized prostate cancer before radical prostatectomy (n = 30) or brachytherapy (n = 40). CTCs were also detected in 3 of 13 patients (23%) with an undetectable serum PSA measured at least 1 year after radical prostatectomy, which is consistent with the expected relapse rate in this setting., Conclusion: CTCs can be detected using telomerase activity in a large majority and a wide variety of patients with prostate cancer, including those with localized disease.

Purpose: To prospectively compare health-related quality of life (HRQOL), patient-reported treatment-related symptoms, and costs of iodine-125 permanent implant interstitial brachytherapy (IB) with those of radical prostatectomy (RP) during the first 2 years after these treatments for localized prostate cancer., Methods and Materials: A total of 435 men with localized low-risk prostate cancer, from 11 French hospitals, treated with IB (308) or RP (127), were offered to complete the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire QLQ-C30 version 3 (EORTC QLQ-C30) and the prostate cancer specific EORTC QLQ-PR25 module before and at the end of treatment, 2, 6, 12, 18, and 24 months after treatment. Repeated measures analysis of variance and analysis of covariance were conducted on HRQOL changes. Comparative cost analysis covered initial treatment, hospital follow-up, outpatient and production loss costs., Results: Just after treatment, the decrease of global HRQOL was less pronounced in the IB than in the RP group, with a 13.5 points difference (p < 0.0001). A difference slightly in favor of RP was observed 6 months after treatment (-7.5 points, p = 0.0164) and was maintained at 24 months (-8.2 points, p = 0.0379). Impotence and urinary incontinence were more pronounced after RP, whereas urinary frequency, urgency, and urination pain were more frequent after IB. Mean societal costs did not differ between IB (8,019 euros at T24) and RP (8,715 euros at T24, p = 0.0843) regardless of the period., Conclusions: This study suggests a similar cost profile in France for IB and RP but with different HRQOL and side effect profiles. Those findings may be used to tailor localized prostate cancer treatments to suit individual patients' needs.

Whereas it has been proposed almost one century ago, brachytherapy for prostate cancer has only recently emerged, especially thanks to endorectal echography, allowing to visualize seed implantation, to the development of seeds for permanent delivery and of micro-sources for high-dose rate delivery, and also to the development of three-dimension dosimetry programs allowing real-time implantations. For selected patients with localized prostate cancer (PSA < 10, Gleason < 7, no extracapsular extension, volume < 50-60 g), prostate brachytherapy with permanent implants (iodine 125 or, less frequently, palladium 103) gives results which appear at 10-15 years comparable to those of surgery. Incontinence and impotence rates appear lower than those of classical surgery. However, the first post-implant months are usually accompanied by urinary toxicity that should not be minimized. High-dose rate brachytherapy (HDR) could find its indications, in combination with conformal radiotherapy, in the treatment of more advanced forms, presenting an intermediate risk. It could also be an alternative to brachytherapy with permanent implants for the low-risk forms mentioned above, especially in developing countries where the cost of radioactive seeds slows down the use of this technique. Brachytherapy for prostate cancer should, therefore, find more and more indications, because of the increased incidence of prostate cancer, due to population ageing, of the increased proportion of localized forms, due to better detection, of the patient's request for less toxicity, and of the expecting lowering of the costs, which are now equivalent to those of surgery and should further lower.

Purpose: To assess the frequency and features of the PSA bounce phenomenon in a series of patients treated with permanent implant brachytherapy for prostate cancer, and to evaluate the percentage of cases in which this bounce could have mimicked a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology consensus criteria., Methods and Materials: From January 1999 to December 2001, 295 patients were treated with a permanent prostate implantation (real-time technique, with free (125)I seeds) by the Paris Institut Curie/Hospital Cochin/Hospital Necker Paris group. Duration of followup is 40.3 months (9-66 months). PSA level was reported at intervals not exceeding 6 months. Bounce was defined by temporary elevation in PSA level, followed by a spontaneous decrease., Results: In our series, 161 patients (55%) showed a transitory PSA increase (bounce) of at least 0.1 ng/mL; 145 patients (49%) a bounce of 0.2 ng/mL; 93 patients (32%) a bounce of 0.4 ng/mL; and 43 patients (15%) a bounce of at least 1 ng/mL. Mean PSA bounce was 0.8 ng/mL (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of total) presented three successive PSA increases, and therefore were to be considered as experiencing a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria. Among those 32 patients, 18 (56%) subsequently showed, without any treatment, a complete normalization of their PSA. In multivariate analysis, age <70 (p<0.0001) and D90>200Gy (p<0.003) were identified as independent factors for a PSA bounce of at least 0.4 ng/mL., Conclusions: The observed rate of 32% of patients showing a PSA bounce of at least 0.4 ng/mL in our series is in good agreement with what has been previously reported in the literature. Among 32 patients fulfilling the classical ASTRO criteria for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, questioning the ASTRO consensus for the biochemical followup of patients undergoing permanent implant prostate brachytherapy.

Purpose: To study the number of migrating seeds, the anatomical site of migration and possible predictive parameters of migration, after prostate cancer brachytherapy using a loose-seed (I125) implantation technique., Patients and Methods: The charts of the 170 patients consecutively treated by the Institut Curie/Hospital Cochin/Hospital Necker Group between September 1, 2001 and August 31, 2002, were analysed. All seeds having migrated to the lungs and seen on the chest X-ray systematically performed at 2 months, have been recorded, as well as the seeds lost by the urines (after sieving) or in the sperm (condom)., Results: Among 12,179 implanted seeds, 44 were found to have migrated (0.36%). Most of the migrating seeds (32/44; 73%), were found in the lungs. Overall, one or several seed migrations were observed in 35 patients (21% of the total number of patients in this series). In the majority of cases (77%), only one seed migrated. A significant relationship (P = 0.04) was found between the number of migrating seeds and the number of implanted ones (or with the prostate volume, but those two parameters were closely linked in our series). More specifically, a significant relationship (P = 0.02) could be demonstrated between the number of seeds implanted at the periphery of the prostate and the number of seeds migrating to the lungs., Conclusion: The percentage of migrating seeds observed in this series is low, actually one of the lowest found in the literature when using the loose-seed technique. There was no clinical consequences and the loss of-usually-only one seed is very unlikely to alter the quality of the dose distribution. However, the predominance of pulmonary migrations in our series led us to slightly modify our implantation technique. We now try to avoid too "peripheral" seed implantations, due to the risk of migration towards the periprostatic veins, and subsequently to the lungs.

Purpose: Real-time ultrasound (US)-based dosimetry performed during (125)I loose seed implantation provides the radiation oncologist with an estimation of the dose distribution at seed insertion. However, for a number of reasons, this distribution may not reflect the real (reference) dosimetry as determined by subsequent CT, usually performed 1-2 months after implantation. The present study compared the two dosimetry data sets (US and CT) to evaluate how predictive extemporaneous US-based dosimetry can be of the real dose distribution., Methods and Materials: A total of 450 patients with prostate cancer were treated with loose (125)I seed implantation between June 1999 and October 2002 by the Institut Curie/Hospital Cochin (Paris) Group. The mean patient age was 65 years. Most patients (74%) had Stage T1c; the stage did not exceed T2b for the others. All patients had a prostate-specific antigen level of <15 ng/mL and was <10 ng/mL for 72%; 84% had a Gleason score of < or =6 and did not exceed 7 for the others; and 56% were treated with neoadjuvant hormonal therapy for a mean of 4.3 months. All patients were treated with loose seed implantation. Real-time US-based dosimetry was performed intraoperatively for all patients. CT-based dosimetry was performed 2 months after implantation, using the VariSeed software. The minimal dose to 90% of the outlined volume (D(90)) and percentage of volume receiving at least 100% of the prescribed dose (V(100)) were calculated with the two methods and compared for all patients., Results: On CT-based dosimetry, the D(90) was found to be > or =145 Gy (range, 115-240 Gy) in all patients except one. A large majority (86%) of patients showed a CT-based V(100) of >95%, and 48% had a V(100) of >98%. The mean CT-based D(90)/US-based D(90) ratio was 1.0 (range, 0.66-1.33). For 89% of the patients, the difference between the two values was <20% and for 62% was <10%. The mean CT-based V(100)/US-based V(100) ratio was 0.98 (range, 0-1.02), with 89% of patients showing a difference of <5%., Conclusion: Our results indicate that the D(90) and V(100) values obtained intraoperatively with our real-time US-based dosimetry are in reasonable agreement with the subsequent values obtained with CT-based dosimetry performed 2 months after implantation. Recent innovations in our dose planning software allowed better control of the longitudinal seed position and could still improve the correlation between real-time US-based dosimetry and the subsequent CT-based dose distribution.

Purpose: We assessed the rate and results of transurethral resection of the prostate (TURP) in patients previously treated with brachytherapy as monotherapy for localized prostate cancer., Materials and Methods: From May 1998 to May 2003, 600 patients with localized prostate cancer were treated with brachytherapy at our institution. Brachytherapy was performed as monotherapy with curative intent for clinically localized prostate cancer without adjuvant treatment in patients with clinical stages T1c (68.4%) or T2a (31.6%) disease. -Iodine and palladium implants were used in 583 and 7 patients, respectively. A real-time interactive implantation technique was used in all but the first 17 patients, who were treated using a preplanned technique., Results: Of the 600 patients 19 (3.1%) underwent TURP after brachytherapy. Among the patients with acute urinary retention the median interval between prostate brachytherapy and urinary retention was 2 months (range 0.5 to 32). No TURP was done within 6 months after implant. The median interval between prostate brachytherapy and TURP was 7 months (range 6 to 41) and median prostate specific antigen (PSA) before TURP was 0.5 ng/ml (range 0.04 to 3.4). In the 19 patients the median weight of resected prostatic tissue was 8 gm (range 2 to 19) and 1 to 11 seeds were removed (median 5). The perioperative and postoperative courses were uneventful. There was no TURP related incontinence. With a median followup of 28 months after brachytherapy (range 7 to 48) no patient had clinical or biochemical evidence of disease progression, and for the group of 19 patients who underwent TURP median serum PSA at the end of followup was 0.38 ng/ml (range 0.03 to 3.4)., Conclusions: After brachytherapy as monotherapy, TURP can be done safely if indicated. In our experience the resection of prostatic tissue along with a limited number of seeds at least 6 months after implantation did not impair PSA based biological and clinical results of brachy-therapy.

HER-2/neu may play a role in prostate carcinogenesis. The aim of this study was to use the expression of HER-2/neu as a molecular marker for the detection of circulating tumour cells (CTCs) in the blood of patients with prostate cancer (PC). Blood samples were collected from 42 patients with PC and nine healthy volunteers. Immunomagnetic beads were used to harvest epithelial cells from peripheral blood mononuclear cells. Total RNA was extracted and reverse transcribed before analysis by real-time PCR with HER-2/neu-specific primers. CTCs were HER-2/neu positive in six out of 11 (54%) patients with metastatic disease and in three out of 31 (9.6%) patients with localised PC (P=0.004). In blood samples from nine healthy volunteers, we detected no expression of HER-2/neu. The present method appears to be minimally invasive, highly sensitive and a specific approach for detecting CTCs in PC. Furthermore, it may help better target HER-2/neu in advanced PC.

Purpose: To study different methods of CT and MR images fusion in patient treated by brachytherapy for localized prostate cancer. To compare the results of the dosimetric study realized on CT slices and images fusion., Materials and Methods: Fourteen cases of patients treated by I125 were retrospectively studied. The CT examinations were realized with contiguous section of 5mm thickness, and MR images were obtained with a surface coil with contiguous section of 3 mm thickness. For the images fusion process, only the T2 weighted MR sequence was used. Two processes of images fusion were realized for each patient, using as reference marks the bones of the pelvis and the implanted seeds. A quantitative and qualitative appreciation was made by the operators, for each patient and both methods of images fusion. The dosimetric study obtained by a dedicated software was realized on CT images and all types of images fusion. The usual dosimetric indexes (D90, V100 and V150) were compared for each type of image., Results: The quantitative results given by the software of images fusion showed a superior accuracy to the one obtained by the pelvic bony reference marks. Conversely, qualitative and quantitative results obtained by the operators showed a better accuracy of the images fusion based on iodine seeds. For two patients out of three presenting a D90 inferior to 145 Gy on CT examination, the D90 was superior to this norm when the dosimetry was based on images fusion, whatever the method used., Conclusion: The images fusion method based on implanted seed matching seems to be more precise than the one using bony reference marks. The dosimetric study realized on images fusion could allow to rectify possible errors, mainly due to difficulties in surrounding prostate contour delimitation on CT images.

Purpose: To identify the factor(s) most predictive of pT3 tumor and those most predictive of a positive endorectal magnetic resonance (MR) imaging result in patients with clinically localized prostate cancer., Materials and Methods: At multivariate analysis, five preoperative clinical parameters-prostate-specific antigen (PSA) level, digital rectal examination (DRE) result, Gleason score and number of involved sextants at transrectal US-guided biopsy, and endorectal MR imaging result-were used to predict pT3 tumor in 336 patients who underwent radical prostatectomy. On the basis of results of the first four examinations, multivariate analysis was performed also to determine predictors of a positive MR imaging study., Results: Significant predictors of pT3 tumor were positive MR imaging result (P < 2 x 10(-8)), more than one sextant involved at biopsy (P < 5 x 10(-5)), and PSA level greater than 10 ng/mL (P < 7 x 10(-3)). Significant predictors of a positive MR imaging result were three or more sextants involved at biopsy (P < 10(-5)), positive DRE result (P < 5 x 10(-3)), and PSA level greater than 10 ng/mL (P < 16 x 10(-3)). In the subgroup of 175 patients who had at least three positive biopsy specimens, the sensitivity of MR imaging was 50% for detection of occult pT3 tumor and 69% for detection of extensive pT3 tumor. The overall specificity of MR imaging was 95%., Conclusion: Endorectal MR imaging seems to be indicated in carefully selected patients-specifically, those with three or more positive biopsy specimens, a palpable tumor, and/or a PSA level greater than 10 ng/mL.

In the last decade, brachytherapy emerged as a particularly appealing new way ot treating localized prostate cancer. Recently published 10-12 years biochemical control results appear to be superimposable to the best percentages achieved by surgery or conformal radiotherapy, with a small percentage of complications. This applied to severely patients. Only patients with T1/T2, PSA < 10 ng/mL, and Gleason score < 7 should be proposed such a treatment. The potential benefit of exploring patients with a endorectal coil MRI is being evaluated. The number of positive biopsies is also a parameter which should probably be considered in the therapeutic choice. Moreover, a prostate volume > 60 g, hip mobility limitations, a urinary obstructive syndrome and previous transurethral resection lead to difficulties in technical implantation and therefore must be taken into account when discussing brachytherapy. In conclusion, for adequately selected patients, brachytherapy offers a particularly applied alternative to surgery and external radiotherapy, with satisfactory long term biochemical control rates and limited complications.

Radical prostatectomy remains the 'golden standard' therapy for localized prostate carcinoma for patients with a survival rate of more than ten years. However, because of the complications inherent in this surgical procedure, prostatectomy is presently increasingly challenged by various radiotherapy procedures. In the last decade, more sophisticated conformal therapy techniques have been proposed for prostate cancer patients. In parallel, for highly selected patients, brachytherapy is being promoted by an increasing number of medical centers. In fact, brachytherapy techniques for prostate cancers can be traced back to 1911, but recently developed techniques offer reliability and reproducibility, with satisfactory results in terms of tumor control and reduced toxicity, in selected patients. We present here the different techniques that are available today in prostate cancer brachytherapy.

The treatment of clinically localized prostate cancer is based on total prostatectomy, radiotherapy or surveillance. The adverse effects of these treatments have led to an increasing interest in alternatives with decreased morbidity. Brachytherapy consists of placing radioactive sources in the prostatic tissue. High doses can therefore be delivered to the cancer while avoiding excessive irradiation of the bladder and rectum. Brachytherapy generally uses permanent implants (Iodine 125 or Palladium 103). The so-called Seattle technique requires planning before implantation, while, in the "ProCeed" technique, the position of the grains is determined at the time of treatment, with the help of a computer programme which determines the dosimetry. Brachytherapy is a reliable and reproducible technique with minimal morbidity, providing 10-year results comparable to those of total prostatectomy.