Erectile function preservation after radiotherapy using a dose-optimization approach on sexual structures for localized prostate cancer.

PURPOSE: Erectile function preservation is an important quality of life factor in patients treated for prostate cancer. A dose-optimization approach on sexual structures was developed and evaluated to limit erectile dysfunction after radiotherapy. MATERIALS AND METHODS: Twenty-three men with localized prostate cancer and no erectile dysfunction were enrolled in the study. All patients received a prescription dose between 76 and 78Gy. Computed tomography/magnetic resonance image registration was used to delineate the prostatic volume and the sexual structures: internal pudendal arteries (IPA), penile bulb and corpus cavernosum. Erectile function was evaluated using the 5-items International Index of Erectile Function (IIEF-5) score every 6 months during the 2 years after radiotherapy and once a year afterwards. No erectile dysfunction, mild erectile dysfunction and severe erectile dysfunction were defined if the IIEF-5 scores were 20-25, 17-19 and < 17, respectively. RESULTS: The mean follow-up was 4.5 years. The mean age of the patients was 66.3 years. At 2 years, 67% of the patients had no erectile dysfunction, 11% had mild erectile dysfunction and 22% had severe erectile dysfunction. No significant difference was found between the patients with and without erectile dysfunction (IIEF-5≥20 and IIEF-5<20, respectively) for any of the parameters: dosimetric values (internal pudendal arteries, penile bulb, corpus cavernosum), age, comorbidity and smoking status. The biochemical-relapse free survival was 100% at 2 years. CONCLUSION: This approach with dose-optimization on sexual structures for localized prostate cancer found excellent results on erectile function preservation after radiotherapy, with 78% of the patients with no or mild erectile dysfunction at 2 years.

The role of radiation therapy for de novo metastatic bladder and renal cancers.

Metastatic bladder and renal cancers account respectively for 2.1% and 1.8% of cancer deaths worldwide. The advent of immune checkpoint inhibitors has revolutionized the management of metastatic disease, by demonstrating considerable improvements in overall survival. However, despite initial sensitivity to immune checkpoint inhibitors for most patients, both bladder and renal cancer are associated with short progression-free survival and overall survival, raising the need for further strategies to improve their efficacy. Combining systemic therapies with local approaches is a longstanding concept in urological oncology, in clinical settings including both oligometastatic and polymetastatic disease. Radiation therapy has been increasingly studied with either cytoreductive, consolidative, ablative or immune boosting purposes, but the long-term impact of this strategy remains unclear. This review intends to address the impact of radiation therapy with either curative or palliative intent, for synchronous de novo metastatic bladder and renal cancers.

Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

[Stereotactic body radiation therapy for primary kidney cancer]. / Radiothérapie stéréotaxique des carcinomes rénaux primitifs.

The incidence of primary renal cancer is increasing, particularly in elderly patients who may have comorbidities and/or a surgical contraindications. Stereotactic body radiotherapy has primarily been evaluated retrospectively to date. The most commonly used dose schedules are 40Gy in five fractions, 42Gy in three fractions, and 26Gy in one fraction. The results in terms of local control and toxicity are very encouraging. The advantages of stereotactic body radiotherapy compared to thermal ablative treatments are its non-invasive nature, absence of general anesthesia, ability to treat larger lesions, and those close to the renal hilum. Prospective evaluations are still necessary.

[Relationship between doses to anatomical structures and erectile dysfunction after radiotherapy for prostate cancer: A systematic review]. / Relations entre doses dans les structures anatomiques et dysfonction érectile après radiothérapie pour un cancer de la prostate : revue systématique de la littérature.

PURPOSE: During prostatic radiotherapy, damage to several anatomical structures could be the cause of erectile dysfunction: corpora cavernosa, internal pudendal arteries, penile bulb, and neurovascular bundles. Numerous studies have analysed the correlations between the dose received by these structures and erectile function. The objective of this article is to make a systematic review on current knowledge. MATERIALS AND METHODS: A systematic review was performed in the Medline database using the search engine PubMed. Keywords for the search included: erectile dysfunction, penile bulb, corpora cavernosa, cavernosum, neurovascular bundles, radiation therapy, cancer, prostate cancer. The selected articles must study a correlation between erectile dysfunction and the dose received by anatomical structures. A total of 152 articles were identified. Of these 152 articles, 45 fulfilled the defined selection criteria. RESULTS: For corpora cavernosa, seven studies were identified, only two studies demonstrated a significant correlation between the dose received by corpora cavernosa and the occurrence of erectile dysfunction. For penile bulb, only 15 of 23 studies showed a correlation. A mean dose on the penile bulb greater than 20Gy was found to be predictive of erectile dysfunction. None of the eight trials concerning neurovascular bundles succeeded to show a correlation between dose and erectile dysfunction. Only one study evaluated the relationship between the dose received by internal pudendal arteries and erectile dysfunction but was found to be negative. However, vessels-sparing studies showed good results on erectile function preservation without compromising the target volume. CONCLUSION: We currently have little data to show a correlation between erectile dysfunction and sexual structures. It would be necessary to have additional prospective studies evaluating the impact of an optimization on these sexual structures on erectile dysfunction.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

External radiotherapy for prostatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.

Candidates to salvage therapy after external-beam radiotherapy of prostate cancer: Predictors of local recurrence volume and metastasis-free survival.

PURPOSE: The purpose of this study was to assess the predictors of metastasis-free survival (MFS) and of the volume of the local recurrence in patients with rising prostate-specific antigen (PSA) serum level after radiotherapy for prostate cancer and referred for prostate magnetic resonance imaging (MRI) and biopsy in view of salvage treatment. MATERIALS AND METHODS: A total of 132 consecutive men (median age, 70 years; IQR, 66-77 years) with rising PSA after prostate radiotherapy who underwent prostate MRI and biopsy in view of salvage treatment between January 2010 and July 2017 were retrospectively evaluated at a single center. MFS predictors were assessed with Cox models. Predictors of the volume of the local recurrence (number of invaded prostate sectors at biopsy) were assessed using Poisson regression among variables available at PSA relapse. RESULTS: At multivariate analysis, an initial Gleason score≥8 (OR=7 [95% confidence interval (CI): 1.2-40]; P=0.03), a recent radiotherapy (OR=17 [95% CI: 3.9-72]; P<0.0001), the use of androgen deprivation therapy at PSA relapse (OR=12.5 [95% CI: 2.8-57]; P=0.001) and the number of invaded prostate sectors (OR=1.5 [95% CI: 1.1-2]; P=0.007) and maximum cancer core length (OR=0.7 [95%CI: 0.6-0.9]; P=0.002) at biopsy performed at PSA relapse were significant MFS predictors. The PSA level at relapse was significant independent predictor of the volume of local recurrence only when used as a continuous variable (P=0.0002) but not when dichotomized using the nadir+2 threshold (P=0.41). CONCLUSION: Pathological and clinical factors can help predict MFS in patients with rising PSA after prostate radiotherapy and candidates to salvage treatment. The PSA level at relapse has strong influence on the local recurrence volume when used as a continuous variable.

Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group.

PURPOSE: The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. MATERIALS AND METHODS: A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. RESULTS: Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 7 (4+3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. CONCLUSION: To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug.

[Indications and outlooks of radiohormonal therapy of high-risk prostate cancers]. / Indications et perspectives de l'hormonoradiothérapie des cancers de prostate à haut risque.

Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies.

[Treatment of primary disease (breast, non-small cell lung and prostate cancers) with irradiation in case of de novo metastatic cancer]. / Traitement de la maladie primitive (cancers du sein, du poumon non à petites cellules et de la prostate), par irradiation, au stade d'emblée métastatique.

The basis of treatment of primary disease in case of metastatic cancer at diagnosis is based on the knowledge of the natural history of the disease, the biology of the primary tumour and its metastases, advances in modern radiotherapy techniques (modulated intensity, stereotactic radiotherapy) in order to improve the survival of patients with advanced disease. The clinical concept of oligometastatic disease at diagnosis has repositioned the interest of local treatment for primitive disease because these patients have a slower evolutionary profile than metastatic disease extended from the outset. This article reviews the indication of radiotherapy as a local treatment for primary cancer in a de novo metastatic diagnosed disease in the case of breast cancer, non-small cell lung cancer and prostate cancer.

[Stereotactic ablative body radiotherapy: Which machine for which therapeutic indication? A focus on prostate cancer]. / Radiothérapie stéréotaxique extracrânienne : quelle machine pour quelle indication ? Stéréotaxie prostatique.

For the last decade, stereotactic body radiotherapy has become a leading treatment for localized prostate cancer. It can be delivered using a wide array of radiotherapy machines. However, although numerous clinical studies, both prospective and retrospective, have been published, the different techniques have never been properly compared. This article aims at giving an overview of the published trials, and at pointing out the major differences between the machines, from a clinical (efficacy end toxicity), technical and radiobiological point of view.

[Combination external beam radiation and brachytherapy boost for prostate cancer]. / Association de radiothérapie externe et de curiethérapie pour les cancers de la prostate.

Brachytherapy as sole treatment is standard of care for D'Amico classification low-risk prostate cancer. For intermediate and high-risk patients, brachytherapy can be associated to external beam radiation therapy to better take into account the risk of extracapsular effraction and/or seminal vesicle involvement. Three randomized studies have shown that this association increases freedom from relapse survival compared to exclusive external beam radiation therapy. This benefit is not shown for overall survival. The addition of a hormonal therapy to this association is most likely mandatory for high-risk patients, and needs to be confirmed for intermediate risk patients. Both high-dose rate and low-dose rate brachytherapy are suitable with similar biochemical disease free survival rates. High-dose rate brachytherapy seems to have a better genitourinary tolerance profile, while low-dose rate brachytherapy is an easier process and has a more widespread expertise.

[Adjuvant radiotherapy for bladder cancer in patients with risk of locoregional recurrence: Who, what and how?] / Radiothérapie adjuvante des tumeurs de vessie à risque de rechute locorégionale : pour qui, pourquoi et comment ?

Radical cystectomy with extended pelvic lymph node dissection remains the standard of care for non-metastatic muscle-invasive bladder cancer. Locoregional control is a key factor in the outcome of patients since it is related to overall survival, metastasis-free survival and specific survival. Locoregional recurrence rate is directly correlated to pathological results and the quality of lymphadenectomy. In addition, while pre- or postoperative chemotherapy improved overall survival, it showed no impact on locoregional recurrence-free survival. Several recent publications have led to the development of a nomogram that predicts the risk of locoregional recurrence, in order to identify patients for which adjuvant radiotherapy could be beneficial. International cooperative groups have then come together to provide the rational for adjuvant radiotherapy, reinforced by recent technical developments limiting toxicity, and to develop prospective studies to reduce the risk of relapse. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer.

[Prostate cancer external beam radiotherapy]. / Radiothérapie externe des cancers prostatiques.

The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy.

[Management of neuroendocrine prostate carcinoma: Literature review]. / Prise en charge des carcinomes neuroendocrines de prostate : revue de la littérature.

Neuroendocrine prostate carcinoma is a rare entity causing both diagnostic and therapeutic issues. There are basically four histological forms (adenocarcinoma with neuroendocrine differentiation, carcinoid tumors, small cell neuroendocrine carcinomas, large cell neuroendocrine carcinomas), which can be pure or mixed associated with prostatic carcinoma. There is no consensus on the management or the prognosis of these various tumor subtypes. We conducted a literature review aiming to determine the potential therapeutic implications.

[Use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the upper urinary tract]. / Quelle place pour la radiothérapie et la chimiothérapie dans le traitement adjuvant des carcinomes urothéliaux des voies excrétrices urinaires supérieures ?

Urothelial carcinomas of the upper urinary tract are rare entities. Surgery remains the mainstay of the management. The use of others therapeutic modalities is not clearly defined yet. However, the frequency of local recurrence and locoregional encourage us to evaluate the indication of adjuvant therapies. We conducted a synthesis of key data in the literature on the use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and ureter. A literature search on PubMed was performed using the following keywords (MeSH) "urothelial carcinoma", "upper urinary tract", "radiation", "chemotherapy", and adjuvant.

Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how?

Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.

Potential interest of developing an integrated boost dose escalation for stereotactic irradiation of primary prostate cancer.

INTRODUCTION: The stereotactic irradiation is a new approach for low-risk prostate cancer. The aim of the present study was to evaluate a schema of stereotactic irradiation of the prostate with an integrated-boost into the tumor. MATERIAL AND METHODS: The prostate and the tumor were delineated by a radiologist on CT/MRI fusion. A 9-coplanar fields IMRT plan was optimized with three different dose levels: 1) 5 × 6.5 Gy to the PTV1 (plan 1), 2) 5 × 8 Gy to the PTV1 (plan 2) and 3) 5 × 6.5 Gy on the PTV1 with 5 × 8 Gy on the PTV2 (plan 3). The maximum dose (MaxD), mean dose (MD) and doses received by 2% (D2), 5% (D5), 10% (D10) and 25% (D25) of the rectum and bladder walls were used to compare the 3 IMRT plans. RESULTS: A dose escalation to entire prostate from 6.5 Gy to 8 Gy increased the rectum MD, MaxD, D2, D5, D10 and D25 by 3.75 Gy, 8.42 Gy, 7.88 Gy, 7.36 Gy, 6.67 Gy and 5.54 Gy. Similar results were observed for the bladder with 1.72 Gy, 8.28 Gy, 7.01 Gy, 5.69 Gy, 4.36 Gy and 2.42 Gy for the same dosimetric parameters. An integrated SBRT boost only to PTV2 reduced by about 50% the dose difference for rectum and bladder compared to a homogenous prostate dose escalation. Thereby, the MD, D2, D5, D10 and D25 for rectum were increased by 1.51 Gy, 4.24 Gy, 3.08 Gy, 2.84 Gy and 2.37 Gy in plan 3 compared to plan 1. CONCLUSIONS: The present planning study of an integrated SBRT boost limits the doses received by the rectum and bladder if compared to a whole prostate dose escalation for SBRT approach.

[Pelvic irradiation in prostate cancer: what place for what volumes?]. / Radiothérapie pelvienne des cancers de la prostate : quelle place pour quels volumes ?

External beam radiotherapy alone is a standard treatment for prostate cancer. According to clinical, histological and biological characteristics of the tumour, lymph node irradiation can be done in combination with irradiation of the prostate. The completion of pelvic irradiation remains controversial and may cause complications by increasing volumes of irradiated healthy tissues. The accuracy of the delineation of lymph node becomes an important issue. This article proposes to take on the characteristics of the pelvic lymph node drainage of the prostate, to review the literature on pelvic irradiation and the definition of volumes to be irradiated.