Focal high-dose-rate brachytherapy for localized prostate cancer: toxicity and preliminary biochemical results.

BACKGROUND: This study aimed to evaluate the outcomes and the toxicity of focal high-dose-rate (HDR) brachytherapy in selected localized prostate cancer patients. METHODS: Fifty patients were treated with focal high-dose-rate brachytherapy between March 2013 and November 2017, representing 5% of the cases treated by our group during this period. Only patients with very limited and localized tumors, according to strict criteria, were selected for the procedure. The prescribed dose for the focal volume was 24 Gy. RESULTS: The treated volume corresponded to a mean value of 32% of the total prostatic volume. The mean focal D90 in our series was 23 Gy (range 16-26 Gy). The mean initial IPSS was 8.2 (range 0-26), at 6 months 7.5 (range 0-23), and at 24 months 6.7 (range 0-18). No acute or late urinary retention was seen. When the ICIQ-SF score was 0 at the end of treatment, it remained nil thereafter at 1 and 2 years for all patients. No intraoperative or perioperative complications occurred. No rectal toxicity was reported after treatment. Of the total patients identified as potent, only three patients had a very slight decrease of the mean IIEF5. The mean initial PSA was 6.9 ng/mL (range 1.9-13.4). At the last follow-up visit, the mean PSA was 3 ng/ml (range 0.48-8.11). CONCLUSION: HDR focal brachytherapy in selected patients with low intermediate-risk prostate cancer could achieve the same satisfactory results in terms of relapse-free survival as conventional whole prostate brachytherapy with less toxicity.

Locally recurrent prostate cancer with RB1/TP53 alterations successfully treated by salvage focal brachytherapy: a case report.

Retinoblastoma transcriptional corepressor 1 (RB1) and tumor protein p53 (TP53) are well-known tumor suppressor genes; their alterations are associated with poor prognosis in human malignancies and quite rare in locally recurrent cases. The patient was a 58-year-old man who was diagnosed with cT1cN0M0 prostate cancer with Gleason score of 3+3=6 and underwent brachytherapy as the initial treatment. Local recurrence was detected in the left lobe of the prostate 154 months later and whole-exome sequencing that was performed at the request of the patient revealed RB1 loss-of-heterozygosity and TP53 p.I162Rfs*27 mutations. He underwent salvage focal brachytherapy with 125I seeds and serum prostate-specific antigen levels has been stabilized without any genitourinary or gastrointestinal toxicity.

Clinical Efficacy and Openness to New Challenges of Low Dose Rate Brachytherapy for Prostate Cancer.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Salvage focal brachytherapy in castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy.

Introduction: Treatment strategy for castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy has not been established. Case presentation: We described a case of castration-resistant prostate cancer with neuroendocrine differentiation after initial external beam radiotherapy followed by salvage androgen deprivation therapy. Magnetic resonance imaging detected recurrence of a suspicious lesion in the left lobe of the prostate, although the prostate-specific antigen level was <0.2 ng/mL. Transperineal prostate saturation needle biopsy detected adenocarcinoma with neuroendocrine differentiation. The patient underwent salvage focal brachytherapy and had a prostate-specific antigen progression-free survival of 20 months with no obvious adverse events. No recurrence has been detected on magnetic resonance imaging for 18 months. Conclusion: Salvage focal brachytherapy for prostate cancer after external beam radiotherapy can be one of the treatment strategies for local recurrence of castration-resistant prostate cancer with neuroendocrine differentiation.

Focal HDR brachytherapy boost to stereotactic radiotherapy (fBTsRT) for prostate cancer: a phase II randomized controlled trial.

BACKGROUND: For patients with a higher burden of localized prostate cancer, radiation dose escalation with brachytherapy boosts have improved cancer control outcomes at the cost of urinary toxicity. We hypothesize that a focal approach to brachytherapy boosts targeting only grossly visualized tumor volumes (GTV) combined with stereotactic radiotherapy will improve quality of life (QoL) outcomes without compromising cancer control. METHODS: 150 patients with intermediate or high-risk prostate cancer will be enrolled and randomized 1:1 in a cohort multiple randomized clinical trial phase 2 design. Patients are eligible if planned for standard-of-care (SOC) high dose rate (HDR) brachytherapy boost to radiotherapy (RT) with GTVs encompassing < 50% of the prostate gland. Those randomly selected will be offered the experimental treatment, consisting of focal HDR brachytherapy boost (fBT) of 13-15 Gy in 1 fraction followed by stereotactic radiotherapy (sRT) 36.25-40 Gy in 5 fractions to the prostate (+/- 25 Gy to the elective pelvis) delivered every other day. The primary endpoint is to determine if fBTsRT is superior to SOC by having fewer patients experience a minimally important decline (MID) in urinary function as measured by EPIC-26 at 1 and 2 years. Secondary endpoints include rates of toxicity measured by Common Terminology Criteria for Adverse Events (CTCAE), and failure-free survival outcomes. DISCUSSION: This study will determine whether a novel approach for the treatment of localized prostate cancer, fBTsRT, improves QoL and merits further evaluation. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04100174 as a companion to registry NCT03378856 on September 24, 2019.

Targeting the cancer lesion, not the whole prostate.

Modern cancer treatment aims to conserve as much healthy tissue as possible. This has been challenging in the treatment of prostate cancer due to the difficulty in imaging the gland and concerns over leaving multifocal cancer untreated. With improvements in imaging and understanding of multifocal prostate cancer evidence now shows accurate treatment of just the primary focus of cancer or the index lesion can control progression or recurrence of the disease. Many different energy sources are now available to target the cancer lesion within the prostate with less significant side-effects on urinary and sexual function compared to radical treatment. Evidence shows that men value these functions highly and would even trade years of life in exchange for preserved retention of continence or erectile function. Focal treatment of prostate cancer aims to provide both cancer control and preservation of sexual and urinary functions so that men do not have to make a choice between the two. This is a treatment option that men clearly want and deserve.

New approach of ultra-focal brachytherapy for low- and intermediate-risk prostate cancer with custom-linked I-125 seeds: A feasibility study of optimal dose coverage.

PURPOSE: To present the feasibility study of optimal dose coverage in ultra-focal brachytherapy (UFB) with multiparametric MRI for low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: UFB provisional dose plans for small target volumes (<7 cc) were calculated on a prostate training phantom to optimize the seeds number and strength. Clinical UFB consisted in a contour-based nonrigid registration (MRI/Ultrasound) to implant a fiducial marker at the location of the tumor focus. Dosimetry was performed with iodine-125 seeds and a prescribed dose of 160 Gy. On CT scans acquired at 1 month, dose coverage of 152 Gy to the ultra-focal gross tumor volume was evaluated. Registrations between magnetic resonance and CT scans were assessed on the first 8 patients with three software solutions: VariSeed, 3D Slicer, and Mirada, and quantitative evaluations of the registrations were performed. Impact of these registrations on the initial dose matrix was performed. RESULTS: Mean differences between simulated dose plans and extrapolated Bard nomogram for UFB volumes were 36.3% (26-56) for the total activity, 18.3% (10-30) for seed strength, and 22.5% (16-38) for number of seeds. Registration method implemented in Mirada performed significantly better than VariSeed and 3D Slicer (p = 0.0117 and p = 0.0357, respectively). For dose plan evaluation between Mirada and VariSeed, D100% (Gy) for ultra-focal gross tumor volume had a mean difference of 28.06 Gy, mean values being still above the objective of 152 Gy. D90% for the prostate had a mean difference of 1.17 Gy. For urethra and rectum, dose limits were far below the recommendations. CONCLUSIONS: This UFB study confirmed the possibility to treat with optimal dose coverage target volumes smaller than 7 cc.

Focal prostate brachytherapy with (103)Pd seeds.

PURPOSE: Examine modifications to seed placement and target margins necessary to accomplish focal brachytherapy with (103)Pd. METHODS: Our proposed focal brachytherapy program will be primarily favorable intermediate-risk patients with a unilateral index lesion confirmed by transperineal template-guided mapping biopsies (TTMB). The dimensions and location of the TTMB core with the index lesion were placed within the 3-D ultrasound planning volume. Implants were planned for the prostate and the focal targets with generous margins. Planning goals were to cover the target with the 125Gy prescription dose and keep D90 (minimum dose covering 90% of the target) between 125% and 150% of the prescription while minimizing urethral and rectal hot spots. Radiobiological parameters - biologically effective dose (BED) and tumor control probability - were integrated over fractional sub-volumes and focal plans compared to whole gland brachytherapy. RESULTS: A typical 30.1cm(3) prostate was expanded to create a 50.6cm(3) planning target volume (PTV) and needed 22 needles containing 86 (103)Pd seeds of strength 3.20U to deliver the prescribed dose. The hemi-prostate required 39 seeds in 12 needles, and the focal core expanded to a target volume of 11.6cm(3) required 29 seeds in 8 needles. All cancerous PTVs and sub volumes had a tumoricidal BED while organs at risk (OAR) met the dose constraints minimizing morbidity. CONCLUSIONS: For this single case study, both hemi-prostate and focal brachytherapy using (103)Pd seeds met the same target dosimetric goals and OAR constraints as whole prostate plans but with the expected reduction in number of seeds and needles.