A Contemporary Analysis of Urethral Recurrence following Radical Cystectomy.

PURPOSE: Oncologic outcomes following urethral recurrence (UR) remain incompletely described, with reports limited by small cohort sizes. We evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. MATERIALS AND METHODS: We reviewed our institutional radical cystectomy (RC) registry to identify patients with UR. Cox proportional hazards regression was used to assess risk factors for UR. Kaplan-Meier and Cox models were used to assess the relationship between UR and CSS/OS as well as to compare outcomes following symptomatic vs asymptomatic presentation of UR. RESULTS: Overall, 2,930 patients underwent RC from 1980 to 2018, with a median postoperative followup of 7.1 years (IQR 2.8-13.1), of whom 144 (4.9%) were subsequently diagnosed with UR. Carcinoma in situ (HR 1.98, 95% CI 1.30-3.04), multifocal disease (HR 1.59, 95% CI 1.07-2.36) and prostatic urethral involvement at RC (HR 3.01, 95% CI 1.98-4.57) were associated with increased risk of UR. UR was associated with decreased CSS (HR 7.30, 95% CI 5.46-9.76) and OS (HR 1.86, 95% CI 1.54-2.24). A total of 63/144 patients were diagnosed with UR based on symptoms, while 104/144 patients with UR underwent urethrectomy. Patients with symptomatic UR had higher tumor stage at urethrectomy (≥pT2 in 13.1% vs 3.1%, p=0.007), while patients with asymptomatic UR experienced longer median CSS (12.1 vs 6.1 years) and OS (8.30 vs 4.82 years; p=0.05 for both). CONCLUSIONS: We identified pathological risk factors for UR after RC and report adverse subsequent survival outcomes for these patients. Presentation with symptomatic UR was associated with higher tumor stage and poorer prognosis, supporting a value to continued urethral surveillance after RC.

Immunotherapy combined with high- and low-dose radiation to all sites leads to complete clearance of disease in a patient with metastatic vaginal melanoma.

A 73-year-old woman with metastatic vaginal mucosal melanoma that had progressed on ipilimumab and nivolumab experienced clinical and radiographic complete response to dual checkpoint inhibitor immunotherapy given in combination with high-dose plus low-dose radiation. General characteristics and treatment options in this disease are highlighted.

Risk factors and oncological outcomes of urethral recurrence in male patients with muscle invasive bladder cancer after radical cystectomy combined with urinary diversion: a propensity score-matched case control study.

BACKGROUND: Radical cystectomy (RC) is the primary treatment strategy for muscle invasive bladder cancer (MIBC). However, it carries a high risk of urethral recurrence (UR) in male patients. The risk factors and oncological outcomes of UR remain unclear. We aimed to identify the risk factors and oncological outcomes of UR in male patients with MIBC after RC combined with urinary diversion. METHODS: After propensity score matching, we evaluated 137 male patients with MIBC who underwent RC combined with urinary diversion at our center between January 1, 2007 and December 31, 2015. Patient demographics, comorbidity, and perioperative data were recorded. Univariate and multivariate Cox proportional hazards regression were used to estimate the hazard ratio and 95% confidence intervals. Cancer-specific survival (CSS) and overall survival (OS) were measured using the Kaplan-Meier curve with log-rank test. P < 0.05 was considered statistically significant. RESULTS: Of the 310 patients, 30 (9.7%) patients underwent UR. In the matched group, the independent risk factors of UR were history of TURB (HR = 3.069, P = 0.018), tumor stage (T3 vs. T2, HR = 3.997, P = 0.014; T4 vs. T2, HR = 2.962, P = 0.015), and tumor multifocality (HR = 2.854, P = 0.011). The CSS and OS of patients with UR were equivalent to the patients without UR (P = 0.295, P = 0.616). CONCLUSION: This propensity score-matched case-control study showed that UR is not rare in male patients with MIBC after RC combined with urinary diversion. We identified three independent risk factors of UR: history of TURB, tumor stage, and tumor mutifocality. The oncological outcomes were equivalent between patients with and without UR. These findings could help improve treatment strategies and follow-up schedules.

The Metastasis of Renal Cell Carcinoma to the Urethra and Local Tumor Recurrence.

We present the case of metastasis of renal cell carcinoma to the urethra in a 77-year-old woman who underwent -nephrectomy 6 years ago due to renal cell carcinoma. After 3 years, she returned to the ward due to a small, palpable nodule in the area of the urethra that turned out to be a cancer of the clear cell carcinoma. Despite the resection of the -lesion with negative margins in the pathology examination, a local regrowth in the same area was diagnosed in the MRI 8 months after the first episode of metastasis and was successfully removed. The patient keeps urine properly.

Isolated Urethral Metastasis From a Primary Ovarian Malignancy.

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest of gynaecological cancers, often manifesting itself at a later stage (stage 3 and 4). Metastases and recurrences tend to be limited to the abdominopelvic cavity, and cutaneous metastases are rare. CASE SUMMARY: We report an interesting case of a 51-year-old who presented 2 years after her initial treatment with surgery and adjuvant chemotherapy for a stage IIB with an isolated recurrence in the external urethral meatus. CONCLUSION: This case highlights the need for clinicians and patients to remain vigilant during follow-up visits to rule out recurrences despite nonspecific symptoms reported by patients.

[Two Cases of Urethral Clear Cell Adenocarcinoma with Suspected Recurrence of Uterine Cancer].

Herein, we report two cases of urethral clear cell carcinoma in two patients who had previously undergone radical hysterectomyfor utetine cancer. Case 1 presented with bloodyvaginal discharge and case 2 presented with acute urinaryretention. Magnetic resonance imaging revealed a periurethral tumor in both cases. Both cases were suspected to be recurrence at first. However, pathological findings of the transurethral resection-biopsyshowed clear cell adenocarcinoma in both cases. Subsequentlyradical cystourethrectomy and pelvic lymphadenectomy were performed in both cases. Surgical findings showed tumor invasion of the vaginal muscularis in case 1 and invasion of the anterior wall of the vagina and bladder neck in case 2. Although adjuvant postoperative therapywas not performed, there has been no evidence of recurrence to date.

Urethral recurrence after cystectomy: current preventative measures, diagnosis and management.

To summarise the current literature on the diagnosis and management of urethral recurrence (UR) after radical cystectomy (RC), as UR after RC is rare but associated with high mortality. With the recently increased use of orthotopic bladder substitution and the questionable benefit of prophylactic urethrectomy, identification of patients at high risk of UR, management of the remnant urethra, and treatment of UR become critical questions. A review of the PubMed database from 1980 to 2014 was performed to identify studies evaluating recurrent urothelial cancer of the urethra after RC. The search terms used included 'urethral recurrence', 'cystectomy' or 'cystoprostatectomy'. Selected studies provided information on the type of urinary diversion performed, the incidence of UR, and the time to UR. Incidence of UR after RC ranges from 1% to 8% with most recurrences occurring within the first 2 years after surgery. Increased risk of UR is associated with involvement of the prostate, tumour multifocality, bladder neck involvement, and cutaneous diversion. The median overall survival after UR ranges from 6 to 54 months and the 5-year disease-specific survival after UR is reported to be between zero and 83%. UR remains a relatively rare event. Current literature suggests that urethral wash cytology may be useful in patients with intermediate- to high-risk of recurrence to enable early detection of non-invasive disease, which may be amenable to conservative therapy before urethrectomy.

Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice.

Recurrence of sigmoid colon carcinoma in the retained urethra after cystectomy: A case report and review of the literature.

Urethral recurrence arising from a primary colorectal adenocarcinoma is rare. Here, we report a case of urethral recurrence of sigmoid colon cancer, which developed after cysto-prostato-sigmoidectomy for sigmoid colon cancer invading the bladder. The patient underwent urethrectomy successfully and is currently tumor-free. Surgeons who follow patients with colorectal cancer invading the bladder should be aware of this case. The early detection of recurrence improves the chances for disease-free survival.

Urethral metastasis from a sigmoid colon carcinoma: a quite rare case report and review of the literature.

BACKGROUND: Urethral metastatic adenocarcinoma is extremely rare. Moreover, only 9 previous cases with metastases from colorectal cancer have been reported to date, and not much information on urethral metastases from colorectum is available so far. CASE PRESENTATION: We report our experience in the diagnosis and the management of the case with urethral metastasis from a sigmoid colon cancer. A 68-year-old man, who underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma four years ago, presented gross hematuria with pain. Urethroscopy identified a papillo-nodular tumor 7 mm in diameter in the bulbar urethra. CT-scan imaging revealed the small mass of bulbous portion of urethra and solitary lung metastasis. Histological examination of the tumor obtained by transurethral resection showed moderately differentiated adenocarcinoma, which was diagnosed as a metastasis of a sigmoid colon carcinoma pathologically by morphological examination. Immunohistochemical analysis of the urethral tumor revealed the positive for cytokertin 20 and CDX2, whereas negative for cytokertin 7. These features were consistent with metastatic adenocarcinoma of the sigmoid colon cancer. As the management of this case with urethral and lung metastasis, 6-cycle of chemotherapy with fluorouracil with leucovorin plus oxaliplatin was administered to the patient, and these metastases were disappeared with no recurrence of disease for 34 months. CONCLUSION: Urethral metastasis from colorectal cancer is a very rare occurrence. However, in the presence of urinary symptoms, the possibility of the urethral metastasis should be considered.

Upper urinary tract and urethral recurrences following radical cystectomy: review of risk factors and outcomes between centres with different follow-up protocols.

PURPOSE: To examine which patient-related and tumour-related characteristics predict upper urinary tract recurrence (UUTR) and urethral recurrence (UR) of bladder cancer post-radical cystectomy (RC). Secondary objective is to evaluate whether or not recurrence patterns are similar between two centres with different post-RC follow-up (F/U) protocols. METHODS: A retrospective cohort study of 574 consecutive patients undergoing radical cystectomy for urothelial carcinoma of the bladder at two tertiary centres was performed. Clinicopathological factors associated with bladder cancer recurrence and patient-related outcomes, including time to recurrence and death, were collected. Risk factors for recurrences were examined using univariate and multivariable regression analyses. Likelihood of recurrence, time to recurrence, and survival were compared. RESULTS: There was a 3.7 % risk of UUTR (21/574) and a 3.6 % risk of UR (18/503) for the combined cohort at a median F/U of 45 months. When controlling for the effects of all variables modelled, female gender was a significant risk factor for UUT recurrence (OR 3.2, 95 % CI 1.0-9.5, p = 0.03) and prostatic urethral involvement was a significant risk factor for urethral recurrence (OR 7.8, 95 % CI 2.2-27.6, p = 0.001). UUTR were similar (p = 0.82) between Turku (8/205) and Toronto (12/369). Urethral recurrences trended (p = 0.06) towards being more common in Turku (9/151, 6.0 %) versus Toronto (9/352, 2.6 %), but no difference in overall survival was demonstrated between sites. CONCLUSION: The frequency of UUT and urethral recurrences post-cystectomy is relatively low and remained stable for the past 15 years. The ideal F/U protocol to maximize patient-survival remains unknown.

[Multiple urethral metastases from prostate adenocarcinoma after radical prostatectomy: a case report and literature review].

OBJECTIVE: To investigate the mechanism and management of multiple urethral metastases from prostate adenocarcinoma after radical prostatectomy. METHODS: We summed up the experience in the management of a case of multiple urethral metastases from prostate adenocarcinoma after radical prostatectomy and reviewed relevant literature. The patient was a 79-year-old male, who had received radical prostatectomy for prostate adenocarcinoma 13 years before, and presented with macrohematuria and dysuria in the past 2 weeks. A nodule (1.0 x 0.5 cm) was found in the urethral meatus. Cystourethroscopy revealed multiple tumors in the urethra and biopsy indicated them to be metastases from prostate adenocarcinoma. The preoperative level of PSA was 3.01 microg/L. As treatment, we performed radical urethrectomy and cystostomy. RESULTS: Postoperative pathology showed multiple metastases of prostate adenocarcinoma to the urethra, involving the urethral sphincter and corpus spongiosum. Immunohistochemistry revealed PSA (+), PsAP(+), AR(+) and CK 7(-). The surgical margin was negative. The patient recovered well postoperatively, with a PSA level of 1.00 microg/L. CONCLUSION: Urethral metastasis of prostate adenocarcinoma after radical prostatectomy is rarely seen clinically. For the treatment of multiple urethral metastases, surgery is the first choice and radical urethrectomy is an appropriate management.

[Recurrence of bladder cancer in remnant urethra and inguinal lymph node metastasis nine years after total cystectomy: a case report].

A 68-year-old man underwent total cystectomy, urethrectomy preserving fossa navicularis, and an Indiana pouch urinary diversion in 1997. The histopathology was UC, G3, pT4 (prostate). Nine years after the operation, he had multiple metastases to the inguinal and paraaortic lymph nodes (LNs), and he complained of erosion around the glans. Histological diagnosis of the glans revealed recurrent UC to the urethra of the glans. We considered the possibility that the inguinal LN metastasis was due to lymphatic spread from a remnant urethral recurrence. Thus, a partial penectomy and inguinal LN dissection were undertaken. Systemic chemotherapy was administered. Remnant urethral recurrence after urethrectomy preserving the fossa navicularis and inguinal LN metastasis are rare.

Management of urethral recurrence after orthotopic urinary diversion.

STUDY TYPE: Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate our experience with urethral recurrences in patients treated by radical cystectomy(RC) and orthotopic neobladder urinary diversion for carcinoma of the bladder. PATIENTS AND METHODS: We retrospectively reviewed the records of patients treated with RC and orthotopic urinary diversion between January 1980 and July 2004. RESULTS: In all, 260 patients underwent RC with a Studer or Hautmann orthotopic urinary diversion; the median (range) follow-up was 5.1 (0-15.6) years. Six patients (2.3%) developed local recurrence of urothelial cancer (UC) within the urethra after this treatment. The median (range) time to presentation with recurrence after RC was 2.4 (0.7-3.6) years for pT1-4 UC. Recurrences were treated with various methods, including transurethral resection, urethrectomy with conversion of neobladder to continent catheterizable diversion, and chemotherapy. At the last follow-up, four of these six patients were alive without disease, one was alive with disease, and one had died from disease. CONCLUSIONS: In our experience, local recurrences involving the urethra are infrequent. Complete surgical excision can provide a good outcome. Neoadjuvant chemotherapy should be considered for recurrences with adverse clinicopathological features.

[Primary metastatic urethral melanoma: a case study]. / Mélanome primitif de l'urètre découvert au stade métastatique: à propos d'un cas.

PURPOSE: Primary urethral melanoma is a rare pathology for which treatment strategies are controversial. The aim of this work was to report a case of metastatic primary urethral melanoma, and to discuss recent data available from literature. MATERIAL AND METHOD: Case study was summarized from the patient's medical chart. Review of literature was performed using the National Center for Biotechnology Information (NCBI) database. RESULTS: We reported the case of an 89-year-old woman who died from a primary metastatic melanoma of the urethra. This pathology encounters for less than 1% of melanomas and has an adverse prognosis. In case of metastasis, specific survival is only of a few months. When localized to the urethra, treatment relies on radical urethrectomy, followed by adjuvant chemo- and immunotherapy. CONCLUSIONS: The modalities of treatment of primary urethral melanoma rely only on reported case studies. When diagnosed at the metastatic stage, reported specific survival does not exceed a few months.

Urethral involvement is associated with higher mortality and local recurrence in vulvar melanoma: a single institutional experience.

Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared with approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow-up data in our institutional databases. Most patients were Caucasian (n = 35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n = 25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 years), those with thin melanomas (≤1 mm), and those with Clark's level II or III tumors had better 5-year survival rates than older patients (65-83 years) and those with thick melanomas (>1 mm) and those with Clark's level IV or V (P ≤ 0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in 15 patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (P = 0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with mortality, pathology excision specimens should be carefully reviewed with attention to urethral involvement as a potentially important prognostic factor.

A phase II study of docetaxel and oxaliplatin for second-line treatment of urothelial carcinoma.

BACKGROUND: Despite high response rates with front-line platinum-based therapies, 80% of patients with metastatic urothelial cancer progress. Multiple agents and couplets have been investigated, but no standard second-line regimen exists. We conducted a phase II study to evaluate the efficacy and safety of docetaxel and oxaliplatin in metastatic urothelial cancer patients who had received prior platinum therapy. PATIENTS AND METHODS: Patients with metastatic urothelial cancer, who had disease progression after platinum therapy, were treated with docetaxel 75 mg/m(2) and oxaliplatin 85 mg/m(2) every 3 weeks until disease progression or intolerable toxicity. RESULTS: Between November 2004 and September 2005, 11 patients were enrolled. All patients had low or intermediate Bajorin risk. The median number of cycles administered was 2 (range 2-8). One patient achieved near complete response. Three patients experienced disease stabilization, resulting in a disease-control rate of 36%. Median overall survival was 7 months. The most common toxicities were fatigue and anemia (50%). CONCLUSION: Second-line docetaxel and oxaliplatin in metastatic urothelial cancer is safe and tolerable but did not achieve an appreciable response rate.

[Metastasic urethral squamous-cell a cancer]. / Carcinoma escamoso de uretra metastático.

Urethral cancer is an infrequent pathology, less than 1% of the genitourinary tumors. It is more frequent in women (4:1), in the sixth or seventh decade of life. The most frequent histology being squamous cell carcinoma. First signs and symptoms usually are more attributable to benign stricture disease, rather than malignicy. The interval between the onset of symptoms and diagnosis may be as long as three years. Therefore most of these tumors are locally advanced at the time of diagnosis with generally poor prognosis despite aggressive treatment. Therapeutic management varies with the stage and location of the lesion. Because of the rarity of this pathology, no consensus has been reached on treatment modalities, but seems to be that must be a multimodal one, including surgery, radiotherapy and chemotherapy. We present the case of an 80 year-old male, with a diagnosis of urethral squamous-cell cancer, locally advanced at the time of diagnosis. Surgery was not feasible. The patient underwent chemotherapy and radiotherapy with evidence of quick progression thereafter.

Ureteral involvement by metastatic malignant disease.

Ureteral metastases from other primary cancers are very rare. Treatment of these metastases is difficult and outcomes are poor. A thorough literature review was done with the aim of finding characteristics that may influence survival rates of patients with ureteral metastases. Systematic literature searches of PubMed and Web of Science were performed in Jan 2019. A total of 79 papers that included 265 patients with cancer metastases to their ureters were finally considered for evidence synthesis. Prostate, bladder, breast, gut cancer and lymphoma were the predominant primary tumors. The median interval time from primary tumor diagnosis to ureter metastasis was 28.5 months. The median survival time after diagnosis of ureter metastasis was 18 months. Risk factors of survival were analyzed. Age, sex, hydronephrosis, ureter side, and segment were not associated with survival. Interval time and treatment were associated with overall survival. Further analysis indicated that patients who underwent surgery had better outcomes.

A Case of Metastatic Prostate Cancer to the Urethra That Resolved After Androgen Deprivation Therapy.

An 83 year-old male with Gleason score 4+3 prostatic adenocarcinoma status post brachytherapy developed obstructive voiding symptoms 9 years after brachytherapy. Prostate-specific antigen was 0.67. Cystoscopy noted multiple papillary urethral tumors concerning for primary urethral carcinoma. Immunophenotype of biopsies supported diagnosis of Gleason score 4+4 prostatic adenocarcinoma. Androgen deprivation therapy was started. Cystoscopy performed 4 years later, for microhematuria workup, noted complete resolution of the urethral tumors. We present a patient with little serum Prostate-specific antigen change with urethral prostatic adenocarcinoma metastasis that resolved after androgen deprivation therapy.