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.

Outcomes of reconstructive urinary tract surgery after pelvic radiotherapy.

Background: Pelvic radiotherapy causes tissue atrophy and fibrosis, leading to urinary tract dysfunction. Tissue ischaemia poses a significant surgical challenge. This study examined the urological sequelae of radiotherapy, types of reconstructive urological surgery (RUS) required and functional outcomes. Methods: A retrospective review was performed of all radiotherapy patients who underwent RUS at a tertiary centre between 2007-2017. Details including time from radiotherapy, pre-operative assessments, type of surgery performed and functional outcome were analysed. Results: Fifty-four patients were identified. The primary malignancy was cervical (32), colorectal (9) and other urogenital/metastatic origins in the remaining cases. Mean time between radiation and RUS was 13 years. Sixty-nine reconstructive surgeries were performed. Twenty-two patients had fistulae, but only 27% were closed and 73% ended with urinary diversion. Eighteen had ureteric strictures, with 56% having associated bladder dysfunction. Twelve (67%) patients had RUS, of whom 83% required bowel interposition, and 33% primary diversion. Nine of 24 patients with contracted bladders were reconstructed and eight remain functionally continent. Renal function stabilised or improved in 87%. Nine patients (17%) had Clavien 3 or 4 complications. Conclusions: A variety of complex, major RUS were required. In 61%, urinary diversion was necessary, with radiotherapy fistulae being a particular challenge and closed in only a third. In total, 37% of patients were reconstructed achieving functional continence and restoration of upper-tract drainage with renal function preservation. This surgery was at a cost of a re-intervention rate of 28% and significant morbidity in 17%. RUS in the radiotherapy field should be performed in centres with experience.

Optimizing the Role of Surgery and Radiation Therapy in Urethral Cancer Based on Histology and Disease Extent.

PURPOSE: Urethral cancer is rare, with limited data guiding treatment. A national hospital-based registry was used to evaluate the role of local therapy in these patients. METHODS AND MATERIALS: We performed a retrospective cohort study of patients who, between 2004 and 20013, received a diagnosis of T0-4N0-2 M0 urethral cancer. Local therapy was radiation therapy (RT), surgery (S), or S and RT (S+RT). The Cox proportional hazards model was used to assess the impact of therapy type on overall survival (primary endpoint). Subgroup analysis by extent of disease (early stage [T0-2 N0] vs locally advanced [T3+ or N+]) and histology was performed. RESULTS: In our study, 2614 patients had a median follow-up of 28 months. Three-year overall survival was 54%. In 501 patients with locally advanced disease, S+RT was associated with improved survival versus S alone (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.42-0.80). There was no difference for patients with squamous cell carcinoma by treatment type, but patients with adenocarcinoma (RT vs S: HR 0.20; 95% CI, 0.07-0.60) or transitional cell carcinoma (S+RT vs S: HR 0.45, 95% CI, 0.26-0.77) had improved OS with RT as part of treatment. In 1705 early-stage patients, there was no association with survival when comparing S+RT versus S. CONCLUSIONS: For patients with locally advanced disease and transitional cell carcinoma undergoing S, the addition of RT is associated with improved overall survival and should be considered. An RT-based approach may be preferred for adenocarcinoma, but there was no clear association with survival by therapy type for squamous cell carcinoma. This study is hypothesis generating; prospective trials are necessary.

The prognostic effect of salvage surgery and radiotherapy in patients with recurrent primary urethral carcinoma.

BACKGROUND: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC). PATIENTS: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5-48). RESULTS: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST). CONCLUSIONS: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.

[Combined Chemotherapy with Radiation was Tolerable and Effective Treatment in Female Octogenarian Patients with Urethral Cancer -Two Case Reports].

We report two octogenarian patients with primary urethral cancer treated with chemotherapy and external beam radiation therapy. An 85-year-old female presented with perineal bleeding. Magnetic resonance imaging (MRI) showed a locally advanced tumor in the urethra. Biopsy was performed and pathologic findings demonstrated squamous cell carcinoma. After receiving one cycle of a half dose of gemcitabine and nedaplatin, the patient received external beam radiation therapy with gemcitabine and nedaplatin treatment followed by two more cycles of chemotherapy. Complete response was achieved. An 87-year-old female presented with vaginal bleeding. MRIrevealed locally advanced urethral tumor with bilateral inguinal lymph node metastases. Scratch and urine cytology of tumor demonstrated squamous cell carcinoma. After the same treatment as in case 1, primary cancer and lymph node metastases were significantly decreased. There have been no signs of recurrence or progression after treatment, and no severe adverse events in either patient during 53 and 26 months'follow up, respectively.

Primary Urethral Plasmacytoma Treated with High-Dose-Rate Brachytherapy: A Case Report.

Primary urethral solitary plasmacytoma is a very rare variant of extramedullary plasmacytoma. In total, only 9 cases have been reported so far. Patients were treated either by surgery or by external radiation therapy. Here, we report on a 22-year-old man, initially presenting with a palpable induration at the penis, intermittent dysuria and haematospermia, which was due to histologically confirmed solitary urethral kappa-restricted plasmacytoma. The patient subsequently underwent percutaneous and endo-urethral high-dose-rate brachytherapy with a total dose of 42 Gy applied in 14 fractions. Besides an uncomplicated urinary tract infection and hyperpigmentation of the penis, the patient tolerated the radiotherapy well and is still free of disease after 15 months follow-up.

RADIATION THERAPY OF A PRESUMPTIVE URETHRAL TRANSITIONAL CELL CARCINOMA IN AN EASTERN GRAY SQUIRREL (SCIURUS CAROLINENSIS).

An adult female Eastern gray squirrel (Sciurus carolinensis), with a previous history of primary renal transitional cell carcinoma treated by nephrectomy, was diagnosed with a metastatic urethral transitional cell carcinoma (TCC) utilizing the veterinary bladder tumor antigen test in combination with other noninvasive diagnostic tests. The squirrel was treated with piroxicam and external beam radiation therapy given in 18 treatments over 30 days to achieve a total of 54 gray. Mild to moderate side effects from the pelvic irradiation were self-limiting and easily managed. Resolution of clinical signs was achieved for approximately 6 mo until recurrence of metastasis. This report represents the first published account of both TCC and external beam radiation therapy in an Eastern gray squirrel.

Prostate-specific antigen response after definitive radiotherapy for Skene's gland adenocarcinoma resembling prostate adenocarcinoma.

OBJECTIVES: To assess prostate-specific antigen response after definitive radiotherapy in a patient with localized Skene's gland adenocarcinoma resembling prostate adenocarcinoma. MATERIALS AND METHODS: A 71-year-old patient was evaluated for a 2 year history of painless hematuria and found to have a localized Skene's gland adenocarcinoma resembling prostate adenocarcinoma with a pre-therapy PSA of 54.52 ng/ul. She elected to undergo definitive radiotherapy holding radical surgery for salvage. She received 73.8 Gy of intensity modulated radiotherapy in 41 fractions. Serum PSA, imaging, and cystoscopy were followed at 6 month intervals for 2.5 years. RESULTS: The PSA decreased to 0.65 ng/ul 32 months after treatment, her clinical symptoms resolved, and on imaging and exam she has no evidence of residual disease. The PSA half life was 6.16 months (r(2) = 0.97). CONCLUSIONS: For this rare tumor we show that PSA is a reliable marker for disease response and also show that definitive radiotherapy can be an option for organ and functional preservation in patients with localized disease. Cases of periurethral adenocarcinomas should be pathologically screened to assess if they are of Skene's gland origin, as our results suggest a radiotherapy treatment paradigm may be appropriate management in a select subgroup of women with periurethral adenocarcinoma.

Divertículo uretral con degeneración maligna: una complicación infrecuente en una dolencia frecuente / Malignant degeneration in a urethral diverticulum: an uncommon complication in a common condition

El divertículo uretral adquirido es una lesión relativamente frecuente en la mujer. Suelen ser asintomáticos pero pueden complicarse, siendo la infección y la formación de cálculos las complicaciones más frecuentes. La degeneración maligna con desarrollo de una tumoración maligna en el divertículo es una complicación rara que debe ser tenida en cuenta. Son pocos los casos descritos en la literatura de desarrollo de neoplasias malignas a partir de divertículos uretrales. Presentamos a continuación un caso de una mujer que fue diagnosticada de una tumoración maligna en un divertículo uretral. Revisamos los hallazgos de imagen de los divertículos uretrales y sus complicaciones (AU)

Acquired urethral diverticula are relatively common in women. They are usually asymptomatic but they can lead to complications; infection and stones are the most common complications. Malignant degeneration with the development of a malignant tumor in the diverticulum is a rare complication that must be taken into account. Few cases of malignant tumors in urethral diverticula have been reported. We present the case of a woman diagnosed with a malignant tumor in a urethral diverticulum. We review the imaging findings for urethral diverticula and the complications that can arise in this condition (AU)

Locally advanced female urethral adenocarcinoma of enteric origin: the role of adjuvant chemoradiation and brief review.

Primary female urethral adenocarcinoma (FUA) is rare and has a poor prognosis. The common manifestations include urethrorrhagia, urinary frequency, dysuria, urethral obstructions, focal tenderness, and urinary tract infection. These symptoms are neither diagnostic nor pathognomonic; therefore, a delay in diagnosis and even a misdiagnosis is hardly uncommon. The histogenesis of FUAs may have derived from urethritis glandularis, Mullerian ducts, Skene's glands, or mixed origins. Tumors of different embryologic origins displayed heterogeneous pathological morphology and immunohistochemistical phenotypes. Because of its rarity and the lack of large-scale studies, there is no current consensus on the optimal treatment of urethral adenocarcinomas. Here, we report two cases of locally advanced FUA of enteric origin. They manifested as slightest warning symptoms of urinary tract infection and stress urinary incontinence, respectively. One patient died of disease progression 2 months after curative operation. The other patient underwent surgery followed by adjuvant irinotecan-containing chemoradiation, and the effect was at least modest. Hence, we recommend adjuvant chemoradiation in locally advanced FUA. Individualizing cancer care of chemoregimens in accordance with the tumor origins may probably be beneficial in FUAs.

Management of adenocarcinoma of the female urethra: case report and brief review.

INTRODUCTION: We present a case of a differentiated adenocarcinoma of the female urethra, which caused dysuria and voiding dysfunction. MATERIALS AND METHODS: A 54-year-old female presented with dysuria and the sensation of incomplete voiding. RESULTS: An ultrasound-guided biopsy showed a urethral carcinoma. A magnetic resonance imaging (MRI) scan showed a high-stage tumor. The patient had a pelvic exenteration. The patient was free of disease after 2 years of follow up. CONCLUSION: Urethral carcinoma is a rare malignancy. A biopsy is necessary to make a diagnosis. MRI is the best imaging for tumor staging. Small tumors are treated with a single modality option including sparing surgery or radiotherapy. Advanced disease should be treated with a multimodality of options including neoadjuvant radiotherapy given concomitantly with chemotherapy followed by surgery.

Carcinoma of the urethra: radiation oncology.

Urethral cancer is a rare but aggressive neoplasm. Early-stage distal lesions can be successfully treated with a single modality. Results for definitive radiotherapy using either or both external beam radiation therapy and brachytherapy have shown excellent cure rates in men and women. The primary advantage of radiotherapy is organ preservation. Advanced tumors, however, have poor outcomes with single modality treatment. Results have been improved using a combination of radiotherapy and chemotherapy, chiefly 5-fluorouracil and mitomycin C. Although literature is limited to case reports because of the rarity of the disease, the markedly improved results compared with older results of surgery with or without radiation warrant consideration.

[A patient with a primary malignant lymphoma surrounding the female urethra].

A 90-year-old female patient presented with dysuria. She was treated with partial excision of the mass protruding from the urethral meatus. Pathological examination revealed non-Hodgkin's malignant lymphoma of the B-cell type. The patient received a total of 42.4 Gy extrabeam irradiation. Our patient was disease-free for 14 months. We reviewed 25 cases of this rare entity reported previously.

Critical discussion of different dose-volume parameters for rectum and urethra in prostate brachytherapy.

PURPOSE: To compare different dose-volume histogram (DVH) parameter concepts used for rectum and urethra. METHODS AND MATERIALS: Thirty-eight postplan CT scans were used to contour the rectum with only one outer contour and as a wall structure. DVH analysis included dose to absolute and relative volumes of both contour types, from RD(0.1cc) to RD(10cc) and from RDmax to RD30, respectively. Volume parameters are reported (RV50-RV300) in cubic centimeters and percentages. The analysis of urethral dose parameters was based on 55 CTs with a urethral catheter. Relative (UD100 to UDmax) and absolute volume parameters (UD(0.5cc) to UD(0.1cc), UV100, UV150) were evaluated, and also correlated to prostate parameters. The analysis was repeated for 10 MRI-based interstitial high-dose rate cases. RESULTS: The correlation between organ and wall results was high for RD1, RD(2cc), and RD(0.1cc), with differences of <5%. DVH parameters reporting dose to a relative volume (e.g., RD10) or a relative volume related to a certain dose (e.g., RV100 [%]) are sensitive to the number of contoured slices. Dmax has a high uncertainty due to the sampling algorithm. RV100 (145Gy) of 1.5cc is similar to an RD(2cc) of 130Gy. The urethral UD10 and UD(0.1cc) correlate with a mean difference of 1%. The ratios of UD5/UD30, UD10/UD30, and UD5/UD10 were 1.12, 1.09, and 1.03, respectively. The correlation between D90 and D10 for prostate to urethra UD10 was poor. CONCLUSIONS: Only absolute volume parameters are stable in relation to different contouring concepts. When delineating the outer rectum contour, only RD(2cc) and RD(0.1cc) can be used. RV(100) in cc correlates to RD(2cc). Reporting UD5, UD10, and UD30 together is redundant. Additional information is given when reporting UV100 or UV150.

Gluteopopliteal bypass for a compromised groin.

Extra-anatomic arterial reconstruction is indicated in patients with a compromised groin. Surgical options include obturator or transosseous bypass. We present a case of a patient with a necrotic radiation ulcer in the groin treated with a gluteopopliteal bypass.

Adjuvant intraoperative electron radiotherapy and external beam radiotherapy for locally advanced transitional cell carcinoma of the ureter.

OBJECTIVE: Surgery is the mainstay treatment for transitional cell carcinoma (TCC) of the ureter; however, local recurrence remains a common cause of treatment failure for locally advanced disease after surgery, and the benefit of adjuvant radiotherapy has not been completely determined. The objective of this analysis was to evaluate the outcome of postsurgical high dose radiotherapy consisting of intraoperative electron beam radiotherapy (IOERT) and external beam radiotherapy (EBRT) in locally advanced transitional cell carcinoma of the ureter. METHODS: Seventeen patients with pathologically diagnosed TCC of ureter were treated with nephroureterectomy and adjuvant radiation consisted of IOERT and EBRT according to an institutional research protocol. The dose of IOERT ranged between 10 to 20 Gy (median 14 Gy). Conventional EBRT given with the total dose ranged between 36 and 45 Gy (median 42 Gy). Chemotherapy was utilized in 10 of the 17 patients at the discretion of their primary oncologist. RESULTS: The median follow-up for all patients was 48 months (range, 10-91 months). The overall survivals of the entire group of patients at 1, 3, and 5 years were 82%, 65%, and 46%, respectively. The estimated locoregional control rates at 1, 3, and 5 year were 82%, 64%, and 51%, respectively. Depth of invasion (pT), histological grade, and presence of residual disease were significant prognostic factors in univariate analysis. Multivariate analysis revealed that independent prognostic factors for survival included histological grade (grade 1 + 2 vs. grade 3 + 4; P = 0.03) and presence of residual disease after surgery (R0 vs. R1 or R2 resection; P = 0.053). Acute and long-term adverse effects rated grade 3 or higher were seen in 4 and 2 patients, respectively. No grade 5 toxicity occurred. CONCLUSION: IOERT and EBRT following surgery produced a 51% local control and 46% overall survival rate for locally advanced TCC of ureter at 5 years of follow-up, with acceptable rates of acute and late toxicity. Adjuvant IOERT appears to permit dose escalation safely in patients who received conventional adjuvant EBRT and chemotherapy. This strategy deserves to be optimized and then tested in a prospective trial to learn if it can further improve outcome.

Radiation therapy in urinary cancer: state of the art and perspective.

Invasive urinary tumours are relatively rare, and their treatment may cause important changes in urinary, sexual and social functions. A systematic review of external radiation therapy studies in urinary cancers was performed. This synthesis of the literature is based on data from meta-analyses, randomised and prospective trials and retrospective studies. There are few controlled clinical trials using adjuvant or radical radiotherapy with or without chemotherapy in cancer of the kidney, ureter and urethra. There are several reports on multimodality treatment in invasive bladder cancer: intravesical surgery and neoadjuvant chemotherapy to radiotherapy or concomitant radiochemotherapy with organ preservation. The conclusions reached for renal cancer are controversial, and data on cancers of the urethra and ureter are few and inconclusive. Sufficient data now exist in the literature to demonstrate that conservative management with organ preservation is a valuable alternative to radical cystectomy, the traditional gold standard, in invasive bladder cancer.

Aggressive combined-modality therapy for squamous cell carcinoma of the female urethra.

BACKGROUND: A 48-year old woman presented to an emergency department with acute urinary retention necessitating suprapubic catheterization. INVESTIGATIONS: Pelvic examination under anesthetic by both a urologist and gynecologist, biopsy of the urethral tumor and of the cervix, pathological analysis, MRI of the pelvis, CT of the chest, abdomen and pelvis. DIAGNOSIS: Poorly differentiated squamous cell carcinoma of the urethra, T4N0M0. MANAGEMENT: The patient received two cycles of neoadjuvant TIP (paclitaxel, ifosfamide, cisplatin) chemotherapy, resulting in complete remission, followed by consolidative chemoradiation therapy (radiation therapy given with synchronous weekly cisplatin). She remained relapse-free 48 months after diagnosis, with normal voiding and sexual function.