Oncologic Impact and Safety of Pre-Operative Radiotherapy in Localized Prostate and Bladder Cancer: A Comprehensive Review from the Cancerology Committee of the Association Française d’Urologie

Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.

Evaluation of Microscopic Extension in High-grade Glioma Using Macropathology: Determination of Optimal Clinical Target Volume Margins for Radiotherapy

Introduction: One of the most difficult steps of radiotherapy is to determine the clinical target volume (CTV) based on microscopic extension (ME). In this study, we performed a consecutive macropathologic analysis to assess ME in high-grade glioma (HGG) to determine appropriate CTV margins for radiotherapy.Material and methods: The study included 30 HGG patients with tumors located in non-functional areas, and supra total resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. Meanwhile, in order to validate the feasibility and safety of this model, we prospectively recruited another 30 HGG patients in a 1:1 ratio to receive guideline-based radiotherapy (RT) or model-based RT. The overall response rate (ORR) was evaluated during a follow-up of 14 months.Results: Between June 2017 and July 2019, 652 pathologic slides were analyzed. The mean ME distance was 1.70cm (range, 0.63 to 2.87cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. In our validation cohort, after a mean follow-up of 7.65months, patients in the model RT group had a higher ORR than those in the guideline RT group (66.7% vs. 20%, P = 0.01).Conclusion: ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients.