Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0.

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

Reason for euthanasia in dogs with urothelial carcinoma treated with chemotherapy or radiation therapy or both: A retrospective observational study.

BACKGROUND: Clients want to know the ultimate cause of death in their pet after cancer treatment. The cause of euthanasia and investigation of urinary obstruction in treated dogs with urothelial carcinoma (UC) has not been specifically reported in veterinary literature. HYPOTHESIS/OBJECTIVES: Our hypothesis was that the majority of treated dogs with UC are euthanized secondary to primary tumor factors, such as urinary obstruction. ANIMALS: Fifty-nine client-owned dogs diagnosed with UC. METHODS: Retrospective observational study on clinical signs and disease at euthanasia of dogs with UC treated by radiation therapy or chemotherapy or both. RESULTS: The median overall survival time (OST) of all dogs was 339 days (range, 17-1996; 95% confidence interval [CI], 185-392; interquartile range [IQR], 112-505). Of dogs deemed to have been euthanized because of UC (50/59, 85%), the primary cause was considered to be local progression in 31/50 (62%), most often because of perceived complete or partial urinary obstruction (24/31, 77%). No variables were found to be predictive of urinary obstruction. The overall documented metastatic rate was 56%. In dogs euthanized because of UC, metastasis was deemed to be the cause in 19/50 (38%) dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Regardless of the type of treatment, UC in dogs has a poor prognosis and there is a continuing need to improve treatments that focus on local control of the primary tumor, given its high contribution to the decision for euthanasia. Proactive management to avoid the high frequency of urinary obstruction may be worthy of future investigation.

Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study.

The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.

Current trends in the promising immune checkpoint inhibition and radiotherapy combination for locally advanced and metastatic urothelial carcinoma.

Locally advanced and metastatic urothelial carcinoma (UC) remains a challenging malignancy, though several novel therapeutic drugs have been developed in recent years. Over the past decade, immune checkpoint inhibitors (ICI) have shifted the paradigm of therapeutic strategies for UC; however, only a limited number of patients respond to ICI. Since radiotherapy (RT) is widely known to induce systemic immune activation, it may boost the efficacy of ICI. Conversely, RT also causes exhaustion of cytotoxic T cells, and the activation and recruitment of immunosuppressive cells; ICI may help overcome these immunosuppressive effects. Therefore, the combination of ICI and RT has attracted attention in recent years. The therapeutic benefits of this combination therapy and its optimal regimen have not yet been determined through prospective studies. Therefore, this review article aimed to provide an overview of the current preclinical and clinical studies that illustrate the underlying mechanisms and explore the optimization of the RT regimen along with the ICI and RT combination sequence. We also analyzed ongoing prospective studies on ICI and RT combination therapies for metastatic UC. We noted that the tumor response to ICI and RT combination seemingly differs among cancer types. Thus, our findings highlight the need for well-designed prospective trials to determine the optimal combination of ICI and RT for locally advanced and metastatic UC.

Efficacy and Tolerability of Second-line Pembrolizumab With Radiation Therapy in Advanced Urothelial Carcinoma.

BACKGROUND/AIM: Considering the limited data available on immune checkpoint inhibitors and radiation combination therapy in advanced urothelial carcinoma, this study evaluated the survival benefit and associated toxicity of adding radiation therapy to second-line pembrolizumab. PATIENTS AND METHODS: We retrospectively examined 24 consecutive patients with advanced bladder or upper urinary tract urothelial carcinoma and for whom second-line pembrolizumab was initiated between August 2018 and October 2021 in combination with radiation therapy (with curative intent in 12 patients, and palliative intent in 12 patients). Their survival outcomes and toxicities were compared with those of propensity-score-matched cohorts from a Japanese multicenter study with similar characteristics who received pembrolizumab monotherapy. RESULTS: The median follow-up periods after pembrolizumab initiation were 15 months for the curative cohort and 4 months for the palliative cohort. The median overall survival was 27.7 months for the curative cohort and 4.8 months for the palliative cohort. Compared with the matched pembrolizumab monotherapy cohort, overall survival was better among the curative cohort although not statistically significant (p=0.13), but similar between the palliative and matched pembrolizumab monotherapy cohorts (p=0.44). There was no difference in the incidence of grade ≥2 adverse events between the combination and monotherapy cohorts, irrespective of the intent of radiation therapy. CONCLUSION: The combination of radiation therapy and pembrolizumab can be performed with a clinically acceptable safety profile, and the addition of radiation therapy to immune checkpoint inhibitors may improve survival outcome after pembrolizumab treatment in cases where the intent of radiation therapy is curative.

Is radiotherapy helpful for the prognosis of upper urinary tract urothelial carcinoma? A meta-analysis.

BACKGROUND: At present, the guidelines of the European Society of Urology regarding the use of adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) are not clear, and there are many contradictions in previous research. In addition, several studies on the effect of radiotherapy alone on UTUC patients have been published in recent years, but their results are still inconsistent. To address these problems, we conducted the current meta-analysis. METHOD: Articles were searched in 3 electronic databases: PubMed, Embase and the Cochrane Library. Studies were filtered according to a selection strategy, and data were extracted. Finally, Stata software was used for sensitivity analysis, and Egger's test was used to calculate the stability of the results and determine whether there was publication bias. RESULT: In total, 17 studies involving and 25906 patients were included, adjuvant radiotherapy had no significant effect on patients with UTUC (OS: HR = 1.38 [0.94, 2.03], = P 0.10; CSS: HR = 1.43 [0.92, 2.25], P = 0.11; LRFS: HR = 1.40 [0.99, 1.98], P = 0.06; RFS: HR = 1.19 [0.52, 2.73], P = 0.68; MFS: HR = 1.37 [0.35, 5.31], P = 0.65). Radiotherapy alone had adverse effects on patients with UTUC (OS: HR = 1.25 [1.09, 1.43], P = 0.001, CSS: HR = 1.47 [1.37, 1.59], P < 0.00001). CONCLUSION: Our results show that adjuvant radiotherapy has no significant effect on the prognosis of patients with UTUC, while radiotherapy alone will have an adverse effect on patients with UTUC. In the future, the determination of the tumor stage of patients receiving adjuvant radiotherapy may be an important research direction.

A rare and complete response to combination therapy with radiation and nivolumab in a patient with metastatic urothelial cancer.

According to the current understanding, radiotherapy can enhance the effectiveness of cancer immunotherapy due to radiation-induced release of tumour-associated antigens. Here, we present a case with a metastatic urothelial carcinoma who received nivolumab and palliative radiotherapy to a residual tumour in the vagina and to a large metastatic visceral lymph node. The treatment resulted in a rapid and virtually complete response for the time being in all metastases and in the large parailiac tumour mass. Follow up continues. The presented case demonstrates that the combinatory treatment with radiotherapy and immunotherapy can result in an exceptional response for the benefit of the patient with urothelial cancer. To our knowledge, this is one of the largest metastatic masses to disappear with a combination of immuno-oncologic (nivolumab) and radiation therapies.

Optimal management of recurrent and metastatic upper tract urothelial carcinoma: Implications of intensity modulated radiation therapy.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is rare and the treatment for recurrent or metastatic UTUC is unclear. We evaluated the outcomes of salvage and palliative radiotherapy (RT) and prognostic factors in UTUC patients and find implications for salvage and palliative RT. METHODS: Between August 2006 and February 2021, 174 patients (median age, 68 years; range, 37-90) underwent salvage and palliative RT. Disease status at RT included initially diagnosed advanced disease (n = 8, 4.6%), local recurrence only (n = 56, 32.2%), distant metastasis only (n = 59, 33.9%), and local recurrence and distant metastasis (n = 51, 29.3%). The primary tumor location included the renal pelvis (n = 87, 50%), ureter (n = 77, 44.3%), and both (n = 10, 5.7%). Radical nephroureterectomy, chemotherapy, and immunotherapy were used in 135 (77.6%), 101 (58%), and 19 (10.9%) patients, respectively. Survival outcomes and prognostic factors were analysed using Cox and logistic regression analysis. RESULTS: Salvage RT and palliative RT was administered in 73 (42%) and 101 (58%) patients, respectively. The median radiation dose was 45 Gy (range, 15-65). Two-dimensional (2D) or three-dimensional (3D) RT and intensity modulated RT (IMRT) were used in 61 (35.1%) and 113 (64.9%) patients, respectively. The median follow-up was 7.8 months. The median duration of overall survival (OS) was 13.4 months, and the 1-year OS was 53.5%. The median progression-free survival (PFS) was 4.7 months, and the 6-month PFS was 41.9%. The 6-month infield PFS was 84%. In multivariate analysis, RT method (2D/3D vs. IMRT, p = 0.007) and RT response (p = 0.008) were independent prognostic factors for OS, and RT response correlated with PFS (p = 0.015). In subgroup analysis in patients with PD-L1 data, positive PD-L1 correlated with better PFS (p = 0.009). RT response-associated factors were concurrent chemotherapy (p = 0.03) and higher radiation dose (p = 0.034). Of 145 patients, 10 (6.9%) developed grade 3 acute or late toxicity. CONCLUSIONS: Salvage and palliative RT for UTUC are feasible and effective. Patients with RT response using IMRT may have survival benefit from salvage and palliative RT. Positive PD-L1 status might be related to radiosensitivity. High-dose radiation with concurrent chemotherapy may improve RT response.

Association Between Local Radiation Therapy to the Primary Bladder Tumor and Overall Survival for Patients with Metastatic Urothelial Cancer Receiving Systemic Chemotherapy.

There are limited data on the role of local therapy for metastatic urothelial carcinoma of the bladder (mUC). In this retrospective cohort analysis, we queried the National Cancer Data Base for patients with newly diagnosed mUC (cT1-4 N0-3 M1). Overall survival (OS) was compared between treatment with chemotherapy (CT) alone (n = 4122) and CT plus bladder-directed radiation therapy (CT + RT; n = 337). Multivariable Cox proportional-hazards analyses and matching and landmark analyses were performed. CT + RT was independently associated with better OS (hazard ratio 0.70, 95% confidence interval 0.62-0.79; p < 0.0001) and this result persisted in matched and landmark analyses. These findings are hypothesis-generating and limited by inherent confounding factors; however, a prospective trial evaluating the impact of bladder RT in mUC is warranted. PATIENT SUMMARY: For patients with bladder cancer that has already spread to other parts of the body, it is unclear if radiation therapy directed at the primary bladder tumor would provide any improvement in survival. In this study, we found that aggressive radiation therapy directed at the bladder combined with chemotherapy may provide a survival benefit in some patients with metastatic bladder cancer compared to chemotherapy alone.

Stereotactic Ablative Radiation Therapy for the Treatment of Upper Urinary Tract Urothelial Carcinoma.

PURPOSE: Urothelial carcinomas (UCs), also known as transitional cell carcinomas, account for the majority of upper urinary tract tumors. The gold-standard therapy for operable patients with localized disease is radical nephroureterectomy. However, some patients are not surgical candidates. Data on the use of modern radiation therapy for upper urinary tract UC (UTUC) are scarce. The purpose of this study was to assess the safety and efficacy of SABR in UTUC. METHODS AND MATERIALS: This retrospective study included all patients with UTUC treated with SABR at one institution. Charts were reviewed to evaluate renal function and the development of toxicity using Common Terminology Criteria for Adverse Events, version 3.0. Tumor response on follow-up imaging with computed tomography or magnetic resonance imaging scans was assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: A total of 16 patients (7 patients with UC at the ureter and 9 at the renal pelvis) were identified as treated with SABR. Of the 9 patients with renal pelvis UC, 4 had a previous history of bladder cancer. At the time of treatment, the median age was 85 years (range, 67-95 years). Most patients received 40 Gy in 8 fractions every second day. The median followup was 21 months (range, 3-110 months). Most patients maintained stable renal function, and only 2 patients developed worsening chronic kidney disease, but none required dialysis. Acutely, 4 patients developed grade 1 diarrhea, and 1 patient had new grade 1 hematuria. No chronic side effects were observed. One patient did not have follow-up imaging and was excluded from the tumor-response analysis. Two patients had a complete response of the treated lesion, 9 had a partial response, 2 had stable disease, and 2 had disease progression within the treatment field. CONCLUSIONS: This small case series suggests that SABR for UTUC is safe and well-tolerated, with good radiographic tumor response to ablative doses of radiation therapy.

Adjuvant Radiotherapy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis.

PURPOSE: Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy (RNU) with bladder cuff excision. Neoadjuvant or adjuvant chemotherapy is often used in locally advanced disease. The role of adjuvant radiotherapy (RT), however, remains controversial. To further explore the potential role of adjuvant RT, we performed a systematic review and meta-analysis of the literature from 1990 to present. METHODS AND MATERIALS: We identified 810 candidate articles from database searches, of which 67 studies underwent full-text review, with final inclusion of 20 eligible studies. Among the included studies, there were no randomized controlled trials and a single prospective trial, with the remainder being retrospective series. We performed quantitative synthesis of the results by calculating the pooled odds ratios (OR) for the primary outcome of locoregional recurrence (LRR) and secondary outcomes of overall survival (OS), cancer-specific survival (CSS) and distant recurrence (DR). RESULTS: Adjuvant RT, which was mostly prescribed for locally advanced or margin-positive disease following RNU, significantly reduced locoregional recurrence risk OR 0.43 (95% CI: 0.23-0.70), and the effect remained significant even following subgroup analysis to account for adjuvant systemic therapy. The effect of adjuvant RT on 3-year OS, 5-year CSS and DR was non-significant. However, 5-year OS was unfavourable in the adjuvant RT arm, but study heterogeneity was high, and analysis of small-study effects and subgroups suggested bias in reporting of outcomes. CONCLUSIONS: Adjuvant RT in the setting of locally advanced UTUC improves locoregional control following definitive surgery, but does not appear to improve OS. Higher-quality studies, ideally randomized controlled trials, are needed to further quantify its benefit in this setting, and to explore multi-modal treatments that include systemic agents given concomitantly or sequentially with RT, which may offer an OS benefit in addition to the locoregional control benefit of RT.

Radiotherapy is effective in the management of rare penile metastases: Two case reports.

Penile metastasization is an uncommon condition, mostly derived from primitive advanced abdominal cancers, with disabling symptoms. Palliative treatment, in reason of poor prognosis patients, is frequently surgical with destructive management. We report two cases of penile metastasis, from primitive prostatic adenocarcinoma and primitive urothelial carcinoma, effectively managed with radiation treatment at our institution. A three-dimensional conformal radiation therapy with 42Gy to the planning target volume in 14 fractions was delivered. Radiation treatment was safely delivered, with low toxicity profile and achieved adequate symptoms control without compromising genitourinary functions. Radiation therapy should be considered in management of rare penile metastases.

Predictors of Locoregional Recurrence and Delineation of Adjuvant Radiation Therapy Fields for Patients With Upper Tract Urothelial Carcinoma Receiving Nephroureterectomy.

PURPOSE: To identify factors predictive of locoregional recurrence (LRR) in upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy and to propose adjuvant radiation therapy (ART) fields. METHODS AND MATERIALS: Clinical and pathologic variables for patients receiving nephroureterectomy for UTUC between 1995 and 2009 were analyzed for associations with outcomes. Sites of LRR from all patients with available imaging (39) were contoured on computed tomography image sets of patients with representative anatomy, and ART fields were proposed based on these distributions. RESULTS: A total of 279 patients with a median follow-up of 13.0 years were analyzed. The 5-year cumulative incidence of LRR was 16.7% (95% CI, 12.2-21). Pathologic risk factors (PRFs) associated with increased risk of LRR included tumor in both the renal pelvis and ureter, T stage ≥2, lymph node involvement, grade 3 histology, and positive surgical margins (P < .05). Patients with an increased number of PRFs had a significantly greater risk of LRR. The 5-year cumulative incidence estimates of LRR were 5.3% (95% CI, 1.8%-16.0%), 15.6% (95% CI, 9.5%-25.7%), and 43.9% (95% CI, 31.1%-62.1%) for those with 1, 2, and ≥3 PRFs, respectively. ART fields covering the renal fossa and retroperitoneal lymph nodes from the superior border of L1 through the aortic bifurcation would encompass all sites of LRR for 33 of 46 patients (72%). Non-LRR bladder and distant failure occurred in 101 (36.2%) and 73 (26.2%) of the patients, respectively. The 5-year cumulative incidence estimate of distant failure was 22.5% (95% CI, 17.4%-27.3%). CONCLUSIONS: In patients receiving nephroureterectomy for UTUC, LRR is significantly increased in patients with 2 or more PRFs. These data provide clinically valuable insight into the selection of candidates for ART and the design of ART fields.

Stereotactic Body Radiation Therapy in the Management of Oligometastatic and Oligoprogressive Bladder Cancer and Other Urothelial Malignancies.

AIMS: Bladder cancer represents the most common type of urothelial carcinoma, with a median overall survival of 12.5-15 months in the case of metastatic disease. We evaluated the role of stereotactic body radiation therapy (SBRT) in the management oligometastatic urothelial cancer. MATERIALS AND METHODS: Data on patients with a maximum of five metastases were collected from three institutions. Concomitant systemic therapy was allowed. End points were the local control of treated metastases, distant progression-free survival (PFS), overall PFS and overall survival. RESULTS: Data for 82 lesions and 61 patients were included. The primary tumour was located in the bladder in 82% of patients, followed by kidney pelvis (11.5%). The most common treated site was lung (40.2%). Twenty-nine (47.5%) and 14 (23%) patients received systemic therapy before and during SBRT, respectively. The median BED10 value was 78.7 Gy. The median follow-up was 17.2 months. Rates of local control at 1 and 2 years were 92% and 88.9%, respectively, with correlation with systemic therapy before SBRT (hazard ratio 2.62, P = 0.034). Overall PFS at 1 and 2 years was 47.9% and 38.1%, respectively. The number of metastases was a predictive factor (hazard ratio 2.65, P = 0.008). The median overall survival was 25.6 months. Total dose (hazard ratio 0.93, P = 0.003) and BED10 (hazard ratio 0.97, P = 0.006) were correlated with overall survival. No grade ≥2 adverse events were reported. CONCLUSIONS: SBRT represents an effective and safe treatment in metastatic urothelial carcinoma. Prospective randomised trials are necessary to better evaluate the benefit on delaying the onset of new systemic therapies.

Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response.

PURPOSE: Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer. METHODS: Using the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu/ retrieved ongoing clinical trials on the topic as well. RESULTS: Combination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (≥ 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes. CONCLUSION: RT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited.

A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

[Adjuvant radiotherapy after radical cystectomy for muscle-invasive bladder cancer]. / Place de la radiothérapie adjuvante après cystectomie pour les tumeurs de vessie infiltrant le muscle.

OBJECTIVES: Locoregional relapse (LRR) after cystectomy is a common early event associated with poor prognosis. The role of radiotherapy as an adjunct to radical cystectomy is not well-defined. 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. MATERIAL AND METHODS: An exhaustive review of the literature was carried out using the Pubmed search tool with the following keywords: "radiotherapy" [Mesh], "adjuvant" [Mesh], "local recurrence" [Mesh], "Bladder cancer" [Mesh]. RESULTS: Several recent publications have led to the development of a nomogram that predicts the risk of LRR, in order to identify patients for which adjuvant radiotherapy could be beneficial. Several randomized trials seem to suggest a benefit of radiotherapy, in particular when combined with chemotherapy, in terms of reducing LRR, and may even improve overall survival, with good safety profile. However, there are many biases and the interest of adjuvant radiotherapy in urothelial carcinomas remains debated. CONCLUSION: Prospective trials evaluating adjuvant radiotherapy with current techniques should be undertaken.

Feasibility and Outcomes of Orthotopic Ileal Neobladder Reconstruction Following Pelvic Irradiation.

OBJECTIVES: To evaluate the complications and oncologic outcomes of orthotopic ileal neobladder reconstruction (ONB) following pelvic radiotherapy (RT) compared to patients with no prior pelvic RT. METHODS: Our institutional database was queried for all patients with pT0-4bN0-3M0 urothelial carcinoma of the bladder who underwent radical cystectomy with curative intent and ONB between 1990 and 2018. We then queried this cohort for patients who had prior pelvic RT (>3900 cGy) and compared baseline characteristics, perioperative complications, and recurrence free survival between patients with and without prior pelvic RT. RESULTS: One thousand eight hundred and forty-six patients matched our inclusion criteria; 34 had prior pelvic RT with a median dose of 6280 cGy. Prior RT targeted the bladder, prostate, and cervix in 27, 6, and 1 patient, respectively. Median time from RT to cystectomy was 15.5 months. Patients with prior RT had a longer time from diagnosis to cystectomy, more frequently had ≥5 TURBT and neoadjuvant chemo, and less frequently had multifocal disease. Perioperative complications including operative time, estimated blood loss, days hospitalized, as well as 30- and 90-day complication rates, were not statistically different. There was no statistical difference in recurrence free survival between the 2 groups (P = .48). CONCLUSION: ONB in highly selected patients with prior pelvic RT is feasible with statistically similar perioperative complication rates compared to ONB without prior RT.

A Case study of the radiation therapy treatment of a transitional cell carcinoma of the distal urethra.

Urethral carcinoma is a rare urological cancer, accounting for only 1% of malignancies in Australia. The most common histology is transitional cell carcinoma (TCC). The majority of these cancers are treated with surgery. The main purpose of this case study is to describe a novel radiation treatment technique for treatment of this uncommon cancer. This report details organ-preserving treatment for a distal penile urethral cancer using definitive radiation therapy (RT). In May 2016 a 69-year-old male presented to Crown Princess Mary Cancer Centre (CPMCC) with a small TCC of the distal urethra. The patient was offered numerous treatment options, both radical and organ-preserving approaches, and came to a final decision of a course of radiation therapy despite the lack of randomised evidence to guide treatment in this setting. A dose of 66 Gy in 33 fractions from parallel opposed lateral beams was prescribed to the distal penile urethra. This case required an unusual approach to patient set up to allow access for accurate treatment delivery and to maintain patient comfort. The patient tolerated the full course of radiation therapy with expected skin side effects. He has maintained adequate penile function and is currently free from disease at 33 months with ongoing clinical follow-up.