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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 (PSA10, Gleason7, no extracapsular extension, volume50-60 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.

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.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.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, age70 years (P0.00001) and D90200 Gy (P0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml.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. Age70 years and D90200 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.

Intensity modulated radiation therapy (IMRT) is based on a methodology called inverse planning. Starting from dosimetric objectives, constraints of optimization are fixed and given to the inverse planning system, which in turn calculates the modulated intensity to apply to each beam. Since the algorithms allow the constraints to be violated, the results of optimization may differ from the initial dosimetric objectives. Consequently, the user is compelled to adapt the choice of the constraints according to the type of modulation and until satisfactory results are found. The purpose of this work is to present our experience in the choice of these constraints for prostate cancer treatments, as we moved from conformal radiotherapy to IMRT. Treatments were performed with a Varian 23EX linac and calculations were realized with the Varian CadPlan-Helios planning system.The approach used for the first 12 patients treated at institut Curie with IMRT from June 2002 was analysed. The treatment always consisted of a combination of conformal radiotherapy with and without intensity modulation.Results showed that, a larger fraction of the treatment performed with IMRT induced a better sparing of the organs at risk for the same homogeneous dose distribution to the target volume. Apart from the dose-volume constraint for the rectum, a fixed set of constraints, slightly more restrictive than the dosimetric objectives, could be used for all patients. Compared with conformal radiotherapy, the conformation factor for IMRT increased up to 16%. A specific study was undertaken in view of treatments completely performed with IMRT. The optimal technique consisted in performing separated IMRT plans for the two target volumes, the prostate volume and the prostate plus seminal vesicles volume respectively. Another satisfactory possibility was to define new constraints on two separated planning target volumes, prostate and seminal vesicles. This last approach is now routinely implemented for our IMRT patients.

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.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).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.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.

This retrospective study compared the rate of local recurrence after irradiation of uveal melanoma treated with iodine 125 plaques or proton beam therapy.Iodine 125 plaques were used to treat all uveal melanomas between the end of 1989 and 1991. Since 1991, we have used iodine plaques for small anterior tumors and proton beam for other tumors. We use a plaque with a larger diameter than the tumor diameter (2-4mm) with a dose of 90Gy at the apex. Proton beam therapy is used for all tumors at the equator or posterior to the equator not thicker than 12mm. The dose given is 60Gy cobalt equivalent in four fractions. For each patient, the initial size and location of the tumor were noted as well as the follow-up each year: the outcome for the eye (local recurrence, ocular conservation, and functional results), the occurrence of metastasis, and survival. A statistical analysis was performed.Between December 1989 and September 1998, 1272 patients were treated: 926 (72.8%) were treated with proton beam irradiation and 346 (27.8%) with iodine 125 plaques. The median follow-up was 5 years (60 months). For the patients treated with proton beam therapy, the mean age was 58 years, the tumor location was anterior to the equator for 3.8%, at the equator for 43.6%, and posterior to the equator for 52.6%. The mean tumor diameter was 13.4mm and the mean tumor thickness was 5.69mm. For the patients treated with iodine 125 plaques, the mean age was 61.5 years. The location of the tumor was anterior to the equator for 34.4%, at the equator for 46.5%, and posterior to the equator for 19.1%. The mean tumor diameter was 11.5mm and the mean tumor thickness was 5.12mm. The recurrence rate was 4% for the proton beam treatment and 3.75% for iodine plaques. There was no statistical difference.In the literature, the rate of local recurrence is usually higher with iodine 125 plaques than proton beam therapy. We discuss the risk factors for local recurrence after iodine 125 plaques: tumor diameter, lower dose to the tumor apex and lower dose rate, and posterior location of the tumor. We found a higher mortality rate in patients who presented local recurrence.When we use iodine 125 plaques for anterior tumors with the proper dose and dose rate to the apex of the tumor, we do not find more recurrence than with proton beam therapy.

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.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.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.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.

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, PSA10 ng/mL, and Gleason score7 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 volume60 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.