Original Article
Urachal carcinoma: Clinicopathological features, treatment and outcome ABSTRACT Introduction: Urachal carcinoma is a rare malignancy of urogenital tract. The objective of this study was to assess the clinical presentation, histopathological findings, treatment and outcome of patients of urachal carcinoma at a tertiary care centre. Materials and Methods: A retrospective analysis of six cases of urachal carcinoma diagnosed over a period of 7 years from 2005 to 2011 was carried out. All pathologic specimens were reviewed by a single pathologist. Clinical and histological features along with treatment were reviewed and patient follow‑up and survival outcome was obtained. Results: The mean age at diagnosis was 36 years. Of the six patients, five were male. The tumor was located in dome in five and dome and anterior wall in one patient. All patients underwent partial cystectomy with bilateral pelvic lymph node dissection. The Sheldon pathologic stage was stage II in 1, IIIA in 2, IVA in 3 cases. Five out of six patients received adjuvant radiotherapy. The mean follow‑up period was 37 months. Three out of six were disease free at last follow‑up. Conclusions: Urachal carcinomas are rare and usually locally advanced at presentation with a high risk of distant metastases. Surgery is the primary treatment of choice. Adjuvant therapy may decrease the chances of recurrence but it needs to be elucidated by prospective trials. KEY WORDS: Chemotherapy, radiation therapy, surgery, urachal carcinoma
INTRODUCTION Urachal carcinoma is rare and comprises 0.35 to 0.7% of all bladder cancers and 22 to 35% of vesical adenocarcinomas. [1,2] It arises from malignant transformation of rests of enteric epithelium in the urachus located between dome of the bladder and the umbilicus. It was first described extensively by Begg in 1931. [3] Owing to the rarity, only a few case series have been published. The clinicopathological criteria most helpful in diagnosing urachal carcinoma include tumor in the dome of the bladder, the absence of cystitis cystica and cystitis glandularis, predominant invasion of the muscularis or deeper tissues with a sharp demarcation between the tumor and the surface bladder epithelium, the presence of urachal remnants within the tumor, extension of tumor into the bladder wall with involvement of the space of Rezius, the anterior abdominal wall or the umbilicus, and no evidence of primary neoplasm elsewhere.[2,4] Not all urachal cancers are associated with urachal remnants and some occur in the presence of cystitis cystica or glandularis. As a practical matter, in all patients with adenocarcinoma of bladder dome, urachal cancer should be the working diagnosis until proven otherwise.[5] A few staging systems have
been proposed [6,7] but the one commonly followed is that proposed by Sheldon et al.[2] The mainstay of treatment for these tumors is partial cystectomy with en bloc resection of the median umbilical ligament up to the umbilicus.[8] The goal of the present study was to analyze the clinical and pathological characteristics along with treatment results of this rare entity and to share our experience with literature. Hence, we present a comprehensive description of urachal carcinomas treated at our institute and their outcome.
Narendra Kumar, Divya Khosla, Ritesh Kumar, Arup K. Mandal1, Uma N. Saikia2, Rakesh Kapoor, Shrawan K. Singh1, Suresh C. Sharma Departments of Radiotherapy and Oncology, Regional Cancer Centre, 1Urology, 2 Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India For correspondence: Dr. Divya Khosla, Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh ‑ 160 012, India. E‑mail: dr_divya_ [email protected]
MATERIALS AND METHODS A retrospective analysis of six cases of urachal carcinoma diagnosed over a 7‑year period from 2005 to 2011 was carried out at our institute. The clinical case notes, surgical records, operation notes, and histological slides of these patients were carefully reviewed. The gross and morphological characteristics including location of the tumor, histological subtype, presence of lymphovascular invasion and status of margins were also noted. Tumor staging was performed using staging system of Sheldon et al.[2]: Stage I-no invasion beyond the urachal mucosa; II-invasion confined to the urachus; III-local extension to the (A) bladder,
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Kumar, et al.: Urachal carcinoma
(B) abdominal wall, (C) peritoneum, (D) viscera other than the bladder; and IV-metastasis to (A) regional lymph nodes and (B) distant sites. Follow‑up was calculated from the date of diagnosis until the date of last follow‑up. RESULTS A summary of the clinicopathologic features of patients with urachal carcinoma is shown in Table 1. The mean age of the patients at diagnosis was 36 years (range: 18 to 61 years). Five patients were male and one was female. Hematuria was the predominant finding at presentation in all patients, followed by irritative voiding symptoms in 3, mucinuria in 2, and pain in 1 patient, respectively. The primary investigation was ultrasound of abdomen in all patients. Subsequently, all patients underwent cystoscopy to assess local extension and a contrast‑enhanced computed tomography (CT) for the disease extent. Partial cystectomy was done with a bilateral pelvic lymph node dissection in all and umbilectomy was performed in five out of six patients. Per‑operatively, the tumor was located in the dome of the bladder in five and dome and anterior wall in one patient. The mean tumor size was 6.6 cm (range: 4.5‑12 cm) and two out of six had positive margins. Four patients had lymphovascular space invasion. The stage distribution of the patients was stage II (1 case), IIIA (2 cases) and IVA (3 cases). None of the patients had distant metastasis at the time of presentation. Histopathologically, five patients had mucinous adenocarcinoma and one had adenocarcinoma not otherwise specified (NOS). The histological features are demonstrated in Figure 1 a‑d. The mean follow‑up period was 37 months (range: 21.9 to 64.8 months). Adjuvant radiotherapy was given in five patients. The radiotherapy dose was 50 Gy in 25 fractions in all patients. Adjuvant chemotherapy was given in two patients and consisted of 6 cycles of cisplatin and 5‑fluorouracil. One patient who did not receive adjuvant radiotherapy developed local recurrence and multiple bone metastases with compression at L5 vertebra after 24.9 months. The patient underwent external beam radiotherapy of 40 Gy in 20 fractions (covering lumbar vertebra and pelvis). In view of significant shrunken local lesion on follow‑up CT and pain relief, patient was treated with six cycles of chemotherapy
with paclitaxel and cisplatin. The patient is alive with disease at 48.8 months after radiotherapy and chemotherapy. One patient developed lung and bone metastasis after 16.5 months of surgery and was treated with palliative chemotherapy with gemcitabine and cisplatin and ultimately died of disease. One patient died of lung metastasis. The other three patients are alive and disease free. The treatment, recurrence pattern and status at last follow‑up are summarized in Table 2. DISCUSSION The urachus is the embryological remnant of urogenital sinus and allantois. It usually closes spontaneously by the second trimester, leaving the median umbilical ligament as its remnant. Urachal carcinoma is an aggressive malignancy with limited literature. The prognosis is generally poor because of the obscure anatomic location, late presentation of symptoms leading to advanced stage at diagnosis, propensity for extravesical growth, and high risk of distant metastases. The biologic behavior of urachal cancers favors a long silent course before detection that belies its aggressive nature. Morphologically, all urachal cancers are adenocarcinomas as was seen in our study. Not all adenocarcinomas of the bladder are urachal cancers, only 10 to 40% of bladder
a
b
c
d
Figure 1: Microphotograph showing (a) Ulcerated transitional lining with pools of mucin and single cell infiltration in subepithelium (b) Tumor cells in glandular pattern (c) Tumor cells infiltrating deeper muscle (d) Tumor cells showing signet ring cell morphology with nucleus pushed to periphery (patient 3)
Table 1: Clinicopathological features of individual cases of urachal carcinoma Case 1 2
Age 34 61
Sex M M
3
32
F
4 5 6
26 18 46
M M M
Presenting complaints Gross hematuria Gross hematuria, irritative voiding symptoms, mucinuria Gross hematuria, irritative voiding symptoms, suprapubic pain Gross hematuria, mucinuria Gross hematuria Gross hematuria, irritative voiding symptoms
Location Dome Dome
Histology Mucinous adenocarcinoma Mucinous adenocarcinoma
Dome
Mucinous adenocarcinoma (signet ring cells also present) Mucinous adenocarcinoma Mucinous adenocarcinoma Adenocarcinoma, NOS
Dome+anterior wall Dome Dome
Sheldon stage IVA IIIA IIIA IVA IVA II
M=Male, F=Female, NOS=Not otherwise specified
572
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Kumar, et al.: Urachal carcinoma
Table 2: Treatment, recurrence pattern and status at last follow‑up Case 1 2 3 4 5 6
Surgery PC + PLND PC + PLND PC + PLND PC + PLND PC + PLND PC + PLND
Adjuvant RT Yes Yes No Yes Yes Yes
Adjuvant CCT Yes No No No Yes No
LR No No Yes No No No
DM Yes No Yes Yes No No
FU (in months) 28.6 64.8 48.8 31.7 27.5 21.9
Status at last FU DOD Alive; NED Alive; WD DOD Alive; NED Alive; NED
CCT=Combination chemotherapy, DM=Distant metastasis, DOD=Died of disease, FU=Follow‑up, LR=Local recurrence, NED=No evidence of disease, PC=Partial cystectomy, PLND=Pelvic lymph node dissection, RT=Radiotherapy, WD=With disease
adenocarcinomas are of urachal origin.[4,6,9] The most common histologic subtype of urachal carcinoma reported in various series is adenocarcinoma with enteric features with or without mucin production.[4,10] Factors affecting prognosis of urachal cancer include margin status, lymph node metastasis, stage, distant metastasis and pathological type.[11‑13] Signet ring cell adenocarcinomas and small cell carcinomas are aggressive and tend to display insidious local invasion and dissemination even when they appear to be clinically localized.[14] Urachal cancers tend to have a male predilection.[4,6,15] Our study also showed male predominance (M/F ratio 5:1). The most common clinical feature is hematuria followed by dysuria, abdominal pain, suprapubic mass, and discharge of blood, pus, or mucus from the umbilicus.[4,6,11] Hematuria was the most common presenting symptom followed by irritative voiding symptoms, mucinuria and pain in the present study. Urachal cancers recur in 20 to 38% of patients.[16] The most common sites of recurrence are the pelvis, bladder, and the surgical incision or abdominal wall. Local recurrence is noted most often within 2 years of surgery.[2,15] The most common sites of distant metastasis are lung, bone (particularly the spine), peritoneum (carcinomatosis), lymph nodes and brain.[15] In our series, sites of relapse after surgery were local and bone in 1, lung in 1 and bone and lung in 1 patient. In a population‑based study of 62 individuals of urachal tumor by Pinthus et al., only one patient had cancer localized to the urachus.[7] Primary treatment of localized urachal cancer includes wide local excision of the urachus, umbilicus, and surrounding soft tissue combined with partial or radical cystectomy and bilateral pelvic lymphadenectomy. [7,15] A preoperative diagnosis of urachal tumor helps in planning the surgical approach. In a series by Henly et al.,[5] 5‑year survival rate was 50% after radical cystectomy and 43% after partial cystectomy with no significant differences between the two groups. Sheldon et al.[2] advocated surgical control of the urachal ligament via en bloc excision of the bladder dome, urachal ligament, posterior rectus abdominis fascia and umbilicus. In a recent population based study of 152 patients of urachal cancer, 30% presented with lymph node or distant metastasis. Five‑year overall and relative survival was 45 and 48%, respectively. Prognostic factors for decreased survival include lymph node metastasis, tumor growth in the abdominal wall, peritoneum or adjacent viscera, distant metastases and macroscopic residual tumor.[17]
The role of chemotherapy and radiation therapy is not defined in urachal carcinoma. In a series by Siefker‑Radtke et al.,[18] among the 26 patients who developed metastases, only 4 had significant response to chemotherapy, and of the 9 patients who received chemotherapy with 5‑FU or cisplatin containing regimens, three responded. Role of radiotherapy was not stated in this series. Ashley et al.[15] analyzed 130 patients diagnosed with an urachal mass between 1956 and 2004 at the Mayo clinic, out of which 70 patients had an urachal carcinoma. Sixty patients underwent surgery. Eighteen percent of patients received adjuvant therapies (chemotherapy, radiotherapy or both) for either nodal involvement or positive margins; none of them was associated with better outcome. Primary external beam radiation therapy (median dose, 50 Gy) was administered to six patients. Patients who received primary external beam radiotherapy were having high‑grade tumors with trend toward older patient age and more Stage III and IV tumors. Five‑year cancer‑specific survival was 49%. Thus, authors concluded that role of and radiation therapy in management of urachal cancer is unclear. In a series by Gopalan et al.,[4] three out of 24 patients received adjuvant radiotherapy and all three developed local recurrence. In our series, five out of six who received adjuvant radiotherapy did not develop local recurrence and one who did not receive adjuvant radiation developed local recurrence. Further, multicentric study of the role of adjuvant therapies for optimal management of these rare neoplasms is clearly warranted. The principal limitation of the current study was its small sample size. Because of the relative paucity of patients with urachal cancer, multi‑institutional collaborative studies are required to devise future therapeutic strategies for this tumor. CONCLUSION Urachal cancer is an aggressive neoplasm. Surgery remains the mainstay of therapy. Role of adjuvant treatment is not clearly understood. The optimal management of these tumors is uncertain due to its rarity; however, combined modality treatment can result in prolonged survival and cure. REFERENCES 1. Reuter V. The Urothelial tract: Renal pelvis, ureter, urinary bladder and urethra. Philadelphia: Lippincott Williams and Wilkins; 2004. p. 2062‑3.
Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
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Kumar, et al.: Urachal carcinoma
2. Sheldon CA, Clayman RV, Gonzalez R, Williams RD, Fraley EE. Malignant urachal lesions. J Urol 1984;131:1‑8. 3. Begg RC. The urachus: Its anatomy, histology and development. J Anat 1930;64:170‑83. 4. Gopalan A, Sharp DS, Fine SW, Tickoo SK, Herr HW, Reuter VE, et al. Urachal carcinoma: A clinicopathologic analysis of 24 cases with outcome correlation. Am J Surg Pathol 2009;33:659‑68. 5. Henly DR, Farrow GM, Zincke H. Urachal cancer: Role of conservative surgery. Urology 1993;42:635‑9. 6. Molina JR, Quevedo JF, Furth AF, Richardson RL, Zincke H, Burch PA. Predictors of survival from urachal cancer: A Mayo Clinic study of 49 cases. Cancer 2007;110:2434‑40. 7. Pinthus JH, Haddad R, Trachtenberg J, Holowaty E, Bowler J, Herzenberg AM, et al. Population based survival data on urachal tumors. J Urol 2006;175:2042‑7; discussion 2047. 8. Herr HW, Bochner BH, Sharp D, Dalbagni G, Reuter VE. Urachal carcinoma: Contemporary surgical outcomes. J Urol 2007;178:74‑8; discussion 78. 9. Wright JL, Porter MP, Li CI, Lange PH, Lin DW. Differences in survival among patients with urachal and nonurachal adenocarcinomas of the bladder. Cancer 2006;107:721‑8. 10. Johnson DE, Hodge GB, Abdul‑Karim FW, Ayala AG. Urachal carcinoma. Urology 1985;26:218‑21. 11. Zhang J, Wu J. Options for diagnosis and treatment of urachal
574
carcinoma. Asia Pac J Clin Oncol 2013;9:117‑22. 12. Martínez‑Cornelio A, Flores‑López D, Ojeda RF, Quintero‑Becerra J, Hernández‑Toriz N. Surgical experience with urachal carcinoma. Cir Cir 2009;77:33‑8. 13. Egevad L, Håkansson U, Grabe M, Ehrnstrom R. Urachal signet‑cell adenocarcinoma. Scand J Urol Nephrol 2009;43:88‑91. 14. Loggie BW, Fleming RA, Hosseinian AA. Peritoneal carcinomatosis with urachal signet‑cell adenocarcinoma. Urology 1997;50:446‑8. 15. Ashley RA, Inman BA, Sebo TJ, Leibovich BC, Blute ML, Kwon ED, et al. Urachal carcinoma: Clinicopathologic features and long‑term outcomes of an aggressive malignancy. Cancer 2006;107:712‑20. 16. Besarani D, Purdie CA, Townell NH. Recurrent urachal adenocarcinoma. J Clin Pathol 2003;56:882. 17. Bruins HM, Visser O, Ploeg M, Hulsbergen‑van de Kaa CA, Kiemeney LA, Witjes JA. The clinical epidemiology of urachal carcinoma: Results of a large, population based study. J Urol 2012;188:1102‑7. 18. Siefker‑Radtke AO, Gee J, Shen Y, Wen S, Daliani D, Millikan RE, et al. Multimodality management of urachal carcinoma: The M.D. Anderson Cancer Center experience. J Urol 2003;169:1295‑8. Cite this article as: Kumar N, Khosla D, Kumar R, Mandal AK, Saikia UN, Kapoor R, et al. Urachal carcinoma: Clinicopathological features, treatment and outcome. J Can Res Ther 2014;10:571-4. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
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Urachal carcinoma: Clinicopathological features, treatment and outcome ABSTRACT Introduction: Urachal carcinoma is a rare malignancy of urogenital tract. The objective of this study was to assess the clinical presentation, histopathological findings, treatment and outcome of patients of urachal carcinoma at a tertiary care centre. Materials and Methods: A retrospective analysis of six cases of urachal carcinoma diagnosed over a period of 7 years from 2005 to 2011 was carried out. All pathologic specimens were reviewed by a single pathologist. Clinical and histological features along with treatment were reviewed and patient follow‑up and survival outcome was obtained. Results: The mean age at diagnosis was 36 years. Of the six patients, five were male. The tumor was located in dome in five and dome and anterior wall in one patient. All patients underwent partial cystectomy with bilateral pelvic lymph node dissection. The Sheldon pathologic stage was stage II in 1, IIIA in 2, IVA in 3 cases. Five out of six patients received adjuvant radiotherapy. The mean follow‑up period was 37 months. Three out of six were disease free at last follow‑up. Conclusions: Urachal carcinomas are rare and usually locally advanced at presentation with a high risk of distant metastases. Surgery is the primary treatment of choice. Adjuvant therapy may decrease the chances of recurrence but it needs to be elucidated by prospective trials. KEY WORDS: Chemotherapy, radiation therapy, surgery, urachal carcinoma
INTRODUCTION Urachal carcinoma is rare and comprises 0.35 to 0.7% of all bladder cancers and 22 to 35% of vesical adenocarcinomas. [1,2] It arises from malignant transformation of rests of enteric epithelium in the urachus located between dome of the bladder and the umbilicus. It was first described extensively by Begg in 1931. [3] Owing to the rarity, only a few case series have been published. The clinicopathological criteria most helpful in diagnosing urachal carcinoma include tumor in the dome of the bladder, the absence of cystitis cystica and cystitis glandularis, predominant invasion of the muscularis or deeper tissues with a sharp demarcation between the tumor and the surface bladder epithelium, the presence of urachal remnants within the tumor, extension of tumor into the bladder wall with involvement of the space of Rezius, the anterior abdominal wall or the umbilicus, and no evidence of primary neoplasm elsewhere.[2,4] Not all urachal cancers are associated with urachal remnants and some occur in the presence of cystitis cystica or glandularis. As a practical matter, in all patients with adenocarcinoma of bladder dome, urachal cancer should be the working diagnosis until proven otherwise.[5] A few staging systems have
been proposed [6,7] but the one commonly followed is that proposed by Sheldon et al.[2] The mainstay of treatment for these tumors is partial cystectomy with en bloc resection of the median umbilical ligament up to the umbilicus.[8] The goal of the present study was to analyze the clinical and pathological characteristics along with treatment results of this rare entity and to share our experience with literature. Hence, we present a comprehensive description of urachal carcinomas treated at our institute and their outcome.
Narendra Kumar, Divya Khosla, Ritesh Kumar, Arup K. Mandal1, Uma N. Saikia2, Rakesh Kapoor, Shrawan K. Singh1, Suresh C. Sharma Departments of Radiotherapy and Oncology, Regional Cancer Centre, 1Urology, 2 Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India For correspondence: Dr. Divya Khosla, Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh ‑ 160 012, India. E‑mail: dr_divya_ [email protected]
MATERIALS AND METHODS A retrospective analysis of six cases of urachal carcinoma diagnosed over a 7‑year period from 2005 to 2011 was carried out at our institute. The clinical case notes, surgical records, operation notes, and histological slides of these patients were carefully reviewed. The gross and morphological characteristics including location of the tumor, histological subtype, presence of lymphovascular invasion and status of margins were also noted. Tumor staging was performed using staging system of Sheldon et al.[2]: Stage I-no invasion beyond the urachal mucosa; II-invasion confined to the urachus; III-local extension to the (A) bladder,
Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
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571
Kumar, et al.: Urachal carcinoma
(B) abdominal wall, (C) peritoneum, (D) viscera other than the bladder; and IV-metastasis to (A) regional lymph nodes and (B) distant sites. Follow‑up was calculated from the date of diagnosis until the date of last follow‑up. RESULTS A summary of the clinicopathologic features of patients with urachal carcinoma is shown in Table 1. The mean age of the patients at diagnosis was 36 years (range: 18 to 61 years). Five patients were male and one was female. Hematuria was the predominant finding at presentation in all patients, followed by irritative voiding symptoms in 3, mucinuria in 2, and pain in 1 patient, respectively. The primary investigation was ultrasound of abdomen in all patients. Subsequently, all patients underwent cystoscopy to assess local extension and a contrast‑enhanced computed tomography (CT) for the disease extent. Partial cystectomy was done with a bilateral pelvic lymph node dissection in all and umbilectomy was performed in five out of six patients. Per‑operatively, the tumor was located in the dome of the bladder in five and dome and anterior wall in one patient. The mean tumor size was 6.6 cm (range: 4.5‑12 cm) and two out of six had positive margins. Four patients had lymphovascular space invasion. The stage distribution of the patients was stage II (1 case), IIIA (2 cases) and IVA (3 cases). None of the patients had distant metastasis at the time of presentation. Histopathologically, five patients had mucinous adenocarcinoma and one had adenocarcinoma not otherwise specified (NOS). The histological features are demonstrated in Figure 1 a‑d. The mean follow‑up period was 37 months (range: 21.9 to 64.8 months). Adjuvant radiotherapy was given in five patients. The radiotherapy dose was 50 Gy in 25 fractions in all patients. Adjuvant chemotherapy was given in two patients and consisted of 6 cycles of cisplatin and 5‑fluorouracil. One patient who did not receive adjuvant radiotherapy developed local recurrence and multiple bone metastases with compression at L5 vertebra after 24.9 months. The patient underwent external beam radiotherapy of 40 Gy in 20 fractions (covering lumbar vertebra and pelvis). In view of significant shrunken local lesion on follow‑up CT and pain relief, patient was treated with six cycles of chemotherapy
with paclitaxel and cisplatin. The patient is alive with disease at 48.8 months after radiotherapy and chemotherapy. One patient developed lung and bone metastasis after 16.5 months of surgery and was treated with palliative chemotherapy with gemcitabine and cisplatin and ultimately died of disease. One patient died of lung metastasis. The other three patients are alive and disease free. The treatment, recurrence pattern and status at last follow‑up are summarized in Table 2. DISCUSSION The urachus is the embryological remnant of urogenital sinus and allantois. It usually closes spontaneously by the second trimester, leaving the median umbilical ligament as its remnant. Urachal carcinoma is an aggressive malignancy with limited literature. The prognosis is generally poor because of the obscure anatomic location, late presentation of symptoms leading to advanced stage at diagnosis, propensity for extravesical growth, and high risk of distant metastases. The biologic behavior of urachal cancers favors a long silent course before detection that belies its aggressive nature. Morphologically, all urachal cancers are adenocarcinomas as was seen in our study. Not all adenocarcinomas of the bladder are urachal cancers, only 10 to 40% of bladder
a
b
c
d
Figure 1: Microphotograph showing (a) Ulcerated transitional lining with pools of mucin and single cell infiltration in subepithelium (b) Tumor cells in glandular pattern (c) Tumor cells infiltrating deeper muscle (d) Tumor cells showing signet ring cell morphology with nucleus pushed to periphery (patient 3)
Table 1: Clinicopathological features of individual cases of urachal carcinoma Case 1 2
Age 34 61
Sex M M
3
32
F
4 5 6
26 18 46
M M M
Presenting complaints Gross hematuria Gross hematuria, irritative voiding symptoms, mucinuria Gross hematuria, irritative voiding symptoms, suprapubic pain Gross hematuria, mucinuria Gross hematuria Gross hematuria, irritative voiding symptoms
Location Dome Dome
Histology Mucinous adenocarcinoma Mucinous adenocarcinoma
Dome
Mucinous adenocarcinoma (signet ring cells also present) Mucinous adenocarcinoma Mucinous adenocarcinoma Adenocarcinoma, NOS
Dome+anterior wall Dome Dome
Sheldon stage IVA IIIA IIIA IVA IVA II
M=Male, F=Female, NOS=Not otherwise specified
572
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Kumar, et al.: Urachal carcinoma
Table 2: Treatment, recurrence pattern and status at last follow‑up Case 1 2 3 4 5 6
Surgery PC + PLND PC + PLND PC + PLND PC + PLND PC + PLND PC + PLND
Adjuvant RT Yes Yes No Yes Yes Yes
Adjuvant CCT Yes No No No Yes No
LR No No Yes No No No
DM Yes No Yes Yes No No
FU (in months) 28.6 64.8 48.8 31.7 27.5 21.9
Status at last FU DOD Alive; NED Alive; WD DOD Alive; NED Alive; NED
CCT=Combination chemotherapy, DM=Distant metastasis, DOD=Died of disease, FU=Follow‑up, LR=Local recurrence, NED=No evidence of disease, PC=Partial cystectomy, PLND=Pelvic lymph node dissection, RT=Radiotherapy, WD=With disease
adenocarcinomas are of urachal origin.[4,6,9] The most common histologic subtype of urachal carcinoma reported in various series is adenocarcinoma with enteric features with or without mucin production.[4,10] Factors affecting prognosis of urachal cancer include margin status, lymph node metastasis, stage, distant metastasis and pathological type.[11‑13] Signet ring cell adenocarcinomas and small cell carcinomas are aggressive and tend to display insidious local invasion and dissemination even when they appear to be clinically localized.[14] Urachal cancers tend to have a male predilection.[4,6,15] Our study also showed male predominance (M/F ratio 5:1). The most common clinical feature is hematuria followed by dysuria, abdominal pain, suprapubic mass, and discharge of blood, pus, or mucus from the umbilicus.[4,6,11] Hematuria was the most common presenting symptom followed by irritative voiding symptoms, mucinuria and pain in the present study. Urachal cancers recur in 20 to 38% of patients.[16] The most common sites of recurrence are the pelvis, bladder, and the surgical incision or abdominal wall. Local recurrence is noted most often within 2 years of surgery.[2,15] The most common sites of distant metastasis are lung, bone (particularly the spine), peritoneum (carcinomatosis), lymph nodes and brain.[15] In our series, sites of relapse after surgery were local and bone in 1, lung in 1 and bone and lung in 1 patient. In a population‑based study of 62 individuals of urachal tumor by Pinthus et al., only one patient had cancer localized to the urachus.[7] Primary treatment of localized urachal cancer includes wide local excision of the urachus, umbilicus, and surrounding soft tissue combined with partial or radical cystectomy and bilateral pelvic lymphadenectomy. [7,15] A preoperative diagnosis of urachal tumor helps in planning the surgical approach. In a series by Henly et al.,[5] 5‑year survival rate was 50% after radical cystectomy and 43% after partial cystectomy with no significant differences between the two groups. Sheldon et al.[2] advocated surgical control of the urachal ligament via en bloc excision of the bladder dome, urachal ligament, posterior rectus abdominis fascia and umbilicus. In a recent population based study of 152 patients of urachal cancer, 30% presented with lymph node or distant metastasis. Five‑year overall and relative survival was 45 and 48%, respectively. Prognostic factors for decreased survival include lymph node metastasis, tumor growth in the abdominal wall, peritoneum or adjacent viscera, distant metastases and macroscopic residual tumor.[17]
The role of chemotherapy and radiation therapy is not defined in urachal carcinoma. In a series by Siefker‑Radtke et al.,[18] among the 26 patients who developed metastases, only 4 had significant response to chemotherapy, and of the 9 patients who received chemotherapy with 5‑FU or cisplatin containing regimens, three responded. Role of radiotherapy was not stated in this series. Ashley et al.[15] analyzed 130 patients diagnosed with an urachal mass between 1956 and 2004 at the Mayo clinic, out of which 70 patients had an urachal carcinoma. Sixty patients underwent surgery. Eighteen percent of patients received adjuvant therapies (chemotherapy, radiotherapy or both) for either nodal involvement or positive margins; none of them was associated with better outcome. Primary external beam radiation therapy (median dose, 50 Gy) was administered to six patients. Patients who received primary external beam radiotherapy were having high‑grade tumors with trend toward older patient age and more Stage III and IV tumors. Five‑year cancer‑specific survival was 49%. Thus, authors concluded that role of and radiation therapy in management of urachal cancer is unclear. In a series by Gopalan et al.,[4] three out of 24 patients received adjuvant radiotherapy and all three developed local recurrence. In our series, five out of six who received adjuvant radiotherapy did not develop local recurrence and one who did not receive adjuvant radiation developed local recurrence. Further, multicentric study of the role of adjuvant therapies for optimal management of these rare neoplasms is clearly warranted. The principal limitation of the current study was its small sample size. Because of the relative paucity of patients with urachal cancer, multi‑institutional collaborative studies are required to devise future therapeutic strategies for this tumor. CONCLUSION Urachal cancer is an aggressive neoplasm. Surgery remains the mainstay of therapy. Role of adjuvant treatment is not clearly understood. The optimal management of these tumors is uncertain due to its rarity; however, combined modality treatment can result in prolonged survival and cure. REFERENCES 1. Reuter V. The Urothelial tract: Renal pelvis, ureter, urinary bladder and urethra. Philadelphia: Lippincott Williams and Wilkins; 2004. p. 2062‑3.
Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
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Kumar, et al.: Urachal carcinoma
2. Sheldon CA, Clayman RV, Gonzalez R, Williams RD, Fraley EE. Malignant urachal lesions. J Urol 1984;131:1‑8. 3. Begg RC. The urachus: Its anatomy, histology and development. J Anat 1930;64:170‑83. 4. Gopalan A, Sharp DS, Fine SW, Tickoo SK, Herr HW, Reuter VE, et al. Urachal carcinoma: A clinicopathologic analysis of 24 cases with outcome correlation. Am J Surg Pathol 2009;33:659‑68. 5. Henly DR, Farrow GM, Zincke H. Urachal cancer: Role of conservative surgery. Urology 1993;42:635‑9. 6. Molina JR, Quevedo JF, Furth AF, Richardson RL, Zincke H, Burch PA. Predictors of survival from urachal cancer: A Mayo Clinic study of 49 cases. Cancer 2007;110:2434‑40. 7. Pinthus JH, Haddad R, Trachtenberg J, Holowaty E, Bowler J, Herzenberg AM, et al. Population based survival data on urachal tumors. J Urol 2006;175:2042‑7; discussion 2047. 8. Herr HW, Bochner BH, Sharp D, Dalbagni G, Reuter VE. Urachal carcinoma: Contemporary surgical outcomes. J Urol 2007;178:74‑8; discussion 78. 9. Wright JL, Porter MP, Li CI, Lange PH, Lin DW. Differences in survival among patients with urachal and nonurachal adenocarcinomas of the bladder. Cancer 2006;107:721‑8. 10. Johnson DE, Hodge GB, Abdul‑Karim FW, Ayala AG. Urachal carcinoma. Urology 1985;26:218‑21. 11. Zhang J, Wu J. Options for diagnosis and treatment of urachal
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Journal of Cancer Research and Therapeutics - July-September 2014 - Volume 10 - Issue 3
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