The Clinical Significance of Bone Mineral Density Changes Following Long-Term Androgen Deprivation Therapy in Localized Prostate Cancer Patients.

PURPOSE: Long-term androgen deprivation therapy has been associated with decreased bone mineral density in men with prostate cancer. Some evidence suggests that there is no impact on fracture risk despite this bone mineral density loss. Our study aimed to quantify changes in bone mineral density in men with high risk prostate cancer on long-term androgen deprivation therapy and calcium and vitamin D supplementation. MATERIALS AND METHODS: Bone mineral density analysis was conducted for localized high risk prostate cancer patients enrolled in the phase III randomized trial PCS-V (Prostate Cancer Study 5), comparing conventional and hypofractionated radiation therapy. Patients received 28 months of luteinizing hormone-releasing hormone agonist and calcium and vitamin D supplementation (500 mg calcium BID+400 IU vitamin D3 BID). The areal density and T-scores (spine, femoral neck and total femur) at baseline and 30 months of followup were extracted, and the absolute change was calculated. Clinical bone density status (normal, osteopenia, osteoporosis) was monitored. RESULTS: The lumbar spine, femoral neck and total femoral bone mineral density were measured for 226, 231, and 173 patients, respectively. The mean percent change in bone mineral density was -2.65%, -2.76% and -4.27% for these respective sites (p <0.001 for all). The average decrease in bone mineral density across all sites was -3.2%, with no decline in bone mineral density category in most patients (83%). Eight patients (4%) became osteoporotic. CONCLUSIONS: Despite a mild decline in bone mineral density, the change in clinical bone mineral density category remained low with long-term androgen deprivation therapy. Consequently, calcium and vitamin D supplementation alone may suffice for most localized prostate cancer patients on long-term androgen deprivation therapy.

Urinary Organs at Risk for Prostate Cancer External Beam Radiation Therapy: Contouring Guidelines on Behalf of the Francophone Group of Urological Radiation Therapy.

PURPOSE: The occurrence of genitourinary (GU) toxicity is a common adverse event observed after external beam radiation therapy (EBRT) for prostate cancer (PCa). Recent findings suggest that the dose delivered to specific urinary organs at risk (OARs) such as the ureters, bladder trigone, and urethra is involved in the development of GU toxicity. METHODS AND MATERIALS: A multidisciplinary task force including 3 radiation oncologists, a uroradiologist, and a urologist was created in 2022. First, OARs potentially involved in GU toxicity were identified and discussed. A literature review was performed, addressing several questions relative to urinary OARs: anatomic and radiological definition, radiation-induced injury, and dose-volume parameters. Second, results were presented and discussed with a panel of radiation oncologists and members of the "Francophone Group of Urological Radiation Therapy." Thereafter, the "Francophone Group of Urological Radiation Therapy" experts were asked to answer a dedicated questionnaire, including 35 questions on the controversial issues related to the delineation of urinary OARs. RESULTS: The following structures were identified as critical for PCa EBRT: ureters, bladder, bladder neck, bladder trigone, urethra (intraprostatic, membranous, and spongious), striated sphincter, and postenucleation or posttransurethral resection of the prostate cavity. A consensus was obtained for 32 out of 35 items. CONCLUSIONS: This consensus highlights contemporary urinary structures in both the upper and lower urinary tract to be considered for EBRT treatment planning of PCa. The current recommendations also propose a standardized definition of urinary OARs for both daily practice and future clinical trials.

Managing postoperative biochemical relapse in prostate cancer, from the perspective of the Francophone group of Urological radiotherapy (GFRU).

Up to 50% of patients treated with radical surgery for localized prostate cancer may experience biochemical recurrence that requires appropriate management. Definitions of biochemical relapse may vary, but, in all cases, consist of an increase in a PSA without clinical or radiological signs of disease. Molecular imaging through to positron emission tomography has taken a preponderant place in relapse diagnosis, progressively replacing bone scan and CT-scan. Prostate bed radiotherapy is currently a key treatment, the action of which should be potentiated by androgen deprivation therapy. Nowadays perspectives consist in determining the best combination therapies, particularly thanks to next-generation hormone therapies, but not exclusively. Several trials are ongoing and should address these issues. We present here a literature review aiming to discuss the current management of biochemical relapse in prostate cancer after radical surgery, in lights of recent findings, as well as future perspectives.

Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy.

PURPOSE: Prostate bed (PB) irradiation is considered the standard postoperative treatment after radical prostatectomy (RP) for tumors with high-risk features or persistent prostate-specific antigen, or for salvage treatment in case of biological relapse. Four consensus guidelines have been published to standardize practices and reduce the interobserver variability in PB delineation but with discordant recommendations. To improve the reproducibility in the PB delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked to propose a new and more reproducible consensus guideline for PB clinical target volume (CTV) definition. METHODS AND MATERIALS: A 4-step procedure was used. First, a group of 10 GFRU prostate experts evaluated the 4 existing delineation guidelines for postoperative radiation therapy (European Organization for Research and Treatment of Cancer; the Faculty of Radiation Oncology Genito-Urinary Group; the Radiation Therapy Oncology Group; and the Princess Margaret Hospital) to identify divergent issues. Second, data sets of 50 magnetic resonance imaging studies (25 after RP and 25 with an intact prostate gland) were analyzed to identify the relevant anatomic boundaries of the PB. Third, a literature review of surgical, anatomic, histologic, and imaging data was performed to identify the relevant PB boundaries. Fourth, a final consensus on PB CTV definition was reached among experts. RESULTS: Definitive limits of the PB CTV delineation were defined using easily visible landmarks on computed tomography scans (CT). The purpose was to ensure a better reproducibility of PB definition for any radiation oncologist even without experience in postoperative radiation therapy. CONCLUSIONS: New recommendations for PB delineation based on simple anatomic boundaries and available as a CT image atlas are proposed by the GFRU. Improvement in uniformity in PB CTV definition and treatment homogeneity in the context of clinical trials are expected.

Localization of the surgical bed using supine magnetic resonance and computed tomography scan fusion for planification of breast interstitial brachytherapy.

PURPOSE: To evaluate the feasibility of supine breast magnetic resonance imaging (MR) for definition and localization of the surgical bed (SB) after breast conservative surgery. To assess the inter-observer variability of surgical bed delineation on computed tomography (CT) and supine MR. MATERIALS AND METHODS: Patients candidate for breast brachytherapy and no contra-indications for MR were eligible for this study. Patients were placed in supine position, with the ipsilateral arm above the head in an immobilization device. All patients underwent CT and MR in the same implant/treatment position. Four points were predefined for CT-MRI image fusion. The surgical cavity was drawn on CT then MRI, by three independent observers. Fusion and analysis of CT and MR images were performed using the ECLIPSE treatment planning software. RESULTS: From September 2005 to November 2008, 70 patients were included in this prospective study. For each patient, we were able to acquire axial T1 and T2 images of good quality. Using the predefined fusion points, the median error following the fusion was 2.7 mm. For each observer, volumes obtained on MR were, respectively, 30%, 38% and 40% smaller than those derived from CT images. A highly significant inter-observer variability in the delineation of the SB on CT was demonstrated (p<0.0001). On the contrary, all three observers agreed on the volume of the SB drawn on MR. CONCLUSION: Supine breast MRI yields a more precise definition of the SB with a smaller inter-observer variability than CT and may obviate the need for surgical clips. The volume of the SB is smaller with MRI. In our opinion, CT-MRI fusion should be used for SB delineation, in view of partial breast irradiation.

Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial.

BACKGROUND: Increasing clinical data supports a low α/ß ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. MATERIALS AND METHODS: We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. RESULTS: Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. CONCLUSIONS: Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma.

PURPOSE: To evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT). METHODS: From 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires. RESULTS: Five-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients. CONCLUSIONS: Short split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity.

Salvage treatment with high-dose-rate brachytherapy for isolated vaginal endometrial cancer recurrence.

OBJECTIVE: To evaluate the outcome of patients with recurrent vaginal endometrial cancer treated with high-dose-rate brachytherapy (HDRB) and external beam radiation therapy (EBRT). MATERIALS AND METHODS: The records of all patients diagnosed with endometrial cancer who had presented an isolated vaginal recurrence in our institution between January 1, 1997 and December 30, 2003 were reviewed. Twenty-two patients were identified; 18 (82%) received both EBRT and HDRB, and 4 (18%) received HDRB only. The median EBRT dose prescribed was 45 Gy (range: 44-50.4), and median HDRB was 26 Gy (range: 8-48). Recurrence-free intervals as well as disease-specific survival rates were noted. Complications were assessed in terms of early and late Radiation Therapy Oncology Group toxicity (grade 3 or worse) of the gastrointestinal tract, genitourinary tract and vagina. RESULTS: Median age at recurrence for the 22 patients was 72 years (range: 54-86). Median recurrence time was 20 months (range: 4-135). A complete response was achieved in 100% of patients. After a median follow-up of 32 months (range: 11-78), no patient had locoregional recurrence; 1 developed distant metastasis and died from the disease. Five-year local control, disease-free survival and disease-specific survival were 100%, 96% and 96%, respectively. Four patients (18%) presented grades 3-4 gastrointestinal toxicity, and 11 (50%), grade 3 vaginal toxicity. CONCLUSION: Recurrent vaginal endometrial cancer is amenable to salvage therapy with HDRB and EBRT.