Synchronous and metachronous urothelial carcinoma of the upper urinary tract and the bladder: Are they clonally related? A systematic review

Doeveren, Thomas van; Werken, Harmen J.G. van de; Riet, Job van; Aben, Katja K.H.; Leeuwen, Pim J. van; Zwarthoff, Ellen C.; Boormans, Joost L.

doi:10.1016/j.urolonc.2020.01.008

Cited by 38 publications

(23 citation statements)

References 45 publications

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“…Urothelial carcinomas have been described as a pan-urothelial disease with a propensity to recur throughout these sites. 24,36 As with many other cancers, even intratumoral heterogenicity has been described. 37 However, a recent literature review concluded that most recurrent urothelial tumors are monoclonal which would imply that the mechanism of spread would be intraluminal seeding or intraepithelial migration.…”

Section: Urological Sitesmentioning

confidence: 98%

Bladder and upper urinary tract cancers as first and second primary cancers

Zheng

Sundquist

et al. 2021

Cancer Reports

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Background: Previous population-based studies on second primary cancers (SPCs) in urothelial cancers have focused on known risk factors in bladder cancer patients without data on other urothelial sites of the renal pelvis or ureter.Aims: To estimate sex-specific risks for any SPCs after urothelial cancers, and in reverse order, for urothelial cancers as SPCs after any cancer. Such two-way analysis may help interpret the results. Methods:We employed standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancer associated with urothelial cancers. Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015.Results: We identified 46 234 urinary bladder cancers (75% male), 940 ureteral cancers (60% male), and 2410 renal pelvic cancers (57% male). After male bladder cancer, SIRs significantly increased for 9 SPCs, most for ureteral (SIR 41.9) and renal pelvic (17.2) cancers. In the reversed order (bladder cancer as SPC), 10 individual FPCs were associated with an increased risk; highest associations were noted after renal pelvic (21.0) and ureteral (20.9) cancers. After female bladder cancer, SIRs of four SPCs were significantly increased, most for ureteral (87.8) and pelvic (35.7) cancers. Female bladder, ureteral, and pelvic cancers associated are with endometrial cancer.

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Section: Urological Sitesmentioning

confidence: 98%

Bladder and upper urinary tract cancers as first and second primary cancers

Zheng

Sundquist

et al. 2021

Cancer Reports

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“…Secondly, by intraluminal seeding or intraepithelial spread, cancer cells from the primary UTUC implant in the bladder wall and develop into a UCB resulting in clonally related tumors 3 . Recently, we performed a systematic review of the literature on the clonal relationship between UTUC and paired UCB and found that 94% of the cases originated from the same progenitor cell 4 . However, the molecular techniques used differed largely over time and research groups, plus only a limited number of studies used comprehensive large‐scale DNA sequencing techniques, which enables more conclusive assessment of a clonal relation between these two entities.…”

Section: Introductionmentioning

confidence: 99%

The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

Doeveren

Nakauma-González

Mason

et al. 2020

Intl Journal of Cancer

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The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities.

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“…Such bystander effects of "field cancerization" or "cell competition" are known in many organ systems including the liver, gastro-intestinal and urothelial tracts. 2,[32][33][34] Another mechanism may be local immune suppression of antitumor immune response by activation of FOXP3+ regulatory T cells, M2 macrophages, CD2 dendritic cells and myeloid-derived suppressor cells. 35,36 The suppressive environment may extend to nearby organs and prevail over a period of time.…”

Section: Discussionmentioning

confidence: 99%

Second Primary Cancers After Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers

Zheng¹,

Sundquist²,

Sundquist³

et al. 2021

CLEP

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Background Second primary cancers (SPCs) are important clinically as they may negatively influence patient survival and they may tell about therapeutic side effects and general causes of cancer. Population-based literature concerning SPCs after hepatobiliary cancers is limited and here we assess risks of SPCs after hepatocellular cancer (HCC), and cancers of the gallbladder, bile ducts and ampulla of Vater. In reverse order, we consider the risk of hepatobiliary cancers as SPCs after any cancer. Methods We used standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancers associated with hepatobiliary cancers. Cancer diagnoses were obtained from the Swedish Cancer Registry from years 1990 through 2015. Results We identified 9997 primary HCCs, 1365 gallbladder cancers and 4721 bile duct cancers. After HCC, risks of four SPCs were increased: gallbladder (SIR = 4.38; 95% confidence interval 1.87–8.67), thyroid (4.13; 1.30–9.70), kidney (2.92; 1.66–4.47) and squamous cell skin (1.55; 1.02–2.26) cancers. In reverse order, HCC as SPC, in addition to the above cancers, associations included upper aerodigestive tract, esophageal, small intestinal and bladder cancers and non-Hodgkin lymphoma. For gallbladder and bile duct cancers, associations were found with small intestinal and pancreatic cancers. Conclusion The results suggested that HCC is associated with two types of SPC, one related to shared environmental risk factors, such as alcohol, exemplified by upper aerodigestive tract and esophageal cancer, and the other related to immune dysfunction, exemplified by squamous cell skin cancer. SPCs associated with gallbladder and bile duct cancers suggest predisposition to mutations in the mismatch repair gene MLH1.

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Synchronous and metachronous urothelial carcinoma of the upper urinary tract and the bladder: Are they clonally related? A systematic review

Cited by 38 publications

References 45 publications

Bladder and upper urinary tract cancers as first and second primary cancers

Bladder and upper urinary tract cancers as first and second primary cancers

The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

Second Primary Cancers After Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers

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