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Bladder Cancer - Variant Histology and Non Urothelial Cell Bladder Cancer

Variant Histology Urothelial Cell Carcinoma

Variant histology urothelial cell carcinoma can be more aggressive than UCC.  One study found every month waiting for radical cystectomy increased risk of death by 36%. (12) Classically neoadjuvant chemotherapy was not used, however there is some evidence that there may be benefit  and also some evidence there may be benefit for neoadjuvant pembrolizumab.  There is a difference in outcome for the different variant histology of urothelial cell carcinoma. A very nice 2020 systemic review and meta-analysis reviewed this. (13)

Non-Urothelial Cell Bladder Cancer

URACHAL ADENOCARCINOMA
​Adenocarcinoma is 3rd most common bladder tumor, making up 0.5% to 2.0% of bladder tumors. 10-16% of adenocarcinoma of the bladder are urachal in origin. A Korean retrospective study of 31 patients showed the rate of local or distant recurrence were similar between urachal and non-urachal adenocarcinoma (47.1 vs. 50.0%; P 0.507, log-rank test) and patients with 4-cm tumors had a better disease-free survival than those with 4-cm tumors. Furthermore, mucinous had better DFS and was much more likely in urachal (65% vs 7%). Other studies are contradictory: 1 large study of >1000 patients with adenocarcinoma of the bladder showed that urachal cancer has a significantly better prognosis than non-urachal cancer (2) , 2 studies have reported nonsignificant trends in this direction (3,4) , and a fourth study has found that urachal adenocarcinomas are associated with a significantly worse prognosis (5) . There is no clear consensus on whether urachal is less aggressive than non-urachal adenocarcinoma. (1)  It is unclear if lymphadenectomy, radiation or chemotherapy are of any benefit in urachal carcinoma (9)  however, some experts recommend lymph node dissection and describe neoadjuvant chemotherapy for node positive disease with successful surgery. (11)

​ADENOCARCINIOMA PROGNOSIS 
Small studies have shown various outcomes. A study of 40 patients in Ontario showed 5 and 10yr DSS 61% and 49% (6). MD Anderson study of 42 patients showed only 46% remained disease free at median f/u of 31mo (10).  Mayo showed 5 yr CSS of 49% in 66 patients w/ urachal carcinoma with half of urachal masses malignant and half benign.  15% of malignant patients recurred and 59% had metastasis at some point with the median time to death of 1 year after metastasis.  Not resecting the umbilicus caused a trend towards positive margins. Positive margins and grade were independent predictors of survival.  (9) Sloan Kettering study of 50 patients showed 93% 5yr survival of urachal/bladder confined tumor whereas 69% 5yr survival of extravesical or peri-urachal tumor invasion. (8)  A Netherlands study of 152 patients showed 30% presented with lymph node or distant metastasis. 5yr OS  and RS was 45% and 48%, respectively. (7)  Surgical margins were found to  be one of the most significant factors for outcomes in the Sloan Kettering (8), Mayo (9), and MD Anderson Study (10).  The Ontario study did not assess margins. (6) The Mayo study found no difference between partial and radical cystectomy. (9)  Patients with well differentiated tumors have a 90% 5yr css after surgery. (6)

One ominous prognostic factor is rupture of the cystic contents causing peritoneal carcinomatosis.  The urachal ligament should be resected intact with the umbilicus and the dome of the bladder. (11)

ADENOMCARCINOMA WORKUP
Cystic components are found in ~25% of cancers and do not indicate a benign lesion. (9)  CEA , CA125 and CA19-9 may be helpful as 40-60% of patients with peritoneal carcinomatosis have elevations.  Although the standard of care for adenocarcinoma of the bladder is colonoscopy to rule out metastasis, the authors of one manuscript suggests that if a midline mass in the dome of the bladder is present, this is unlikely metastasis as metastasis rarely affect the bladder dome. (11)

  1. Cho, Sung Yong, et al. "Outcomes of Korean patients with clinically localized urachal or non-urachal adenocarcinoma of the bladder." Urologic Oncology: Seminars and Original Investigations. Vol. 31. No. 1. Elsevier, 2013.
  2. Wright JL, Porter MP, Li CI, et al. Differences in survival among patients with urachal and nonurachal adenocarcinomas of the bladder. Cancer 2006;107:721– 8.
  3. Grignon DJ, Ro JY, Ayala AG, et al. Primary adenocarcinoma of the urinary bladder. A clinicopathologic analysis of 72 cases Cancer 1991;67:2165–72.
  4. Dandekar NP, Dalal AV, Tongaonkar HB, et al. Adenocarcinoma of bladder. Eur J Surg Oncol 1997;23:157– 60.
  5. ​Mostofi FK, Thomson RV, Dean AL Jr. Mucous adenocarcinoma of the urinary bladder. Cancer 1955;8:741–58.
  6. Pinthus, Jehonathan H., et al. "Population based survival data on urachal tumors." The Journal of urology 175.6 (2006): 2042-2047.
  7. Bruins, H. Max, et al. "The clinical epidemiology of urachal carcinoma: results of a large, population based study." The Journal of urology 188.4 (2012): 1102-1107.
  8. Herr, Harry W., et al. "Urachal carcinoma: contemporary surgical outcomes." The Journal of urology 178.1 (2007): 74-78.
  9. Ashley, Richard A., et al. "Urachal carcinoma: Clinicopathologic features and long‐term outcomes of an aggressive malignancy." Cancer 107.4 (2006): 712-720.
  10. ​Siefker-Radtke AO, Gee J, Shen Y, et al. Multimodality management of urachal carcinoma: The M. D. Anderson Cancer Center experience. J Urol 2003;169:1295– 8.
  11. Siefker-Radtke, Arlene. "Urachal adenocarcinoma: a clinician's guide for treatment." Seminars in oncology. Vol. 39. No. 5. WB Saunders, 2012.
  12. ​Lin-Brande, Michael, et al. "Assessing the Impact of Time to Cystectomy for Variant Histology of Urothelial Bladder Cancer." Urology (2019).
  13. ​Mori, Keiichiro, et al. "A Systematic Review and Meta-Analysis of Variant Histology in Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy." The Journal of urology 204.6 (2020): 1129-1140.
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