Surveillance guidelines based on recurrence patterns for upper tract urothelial carcinoma

Locke, Jennifer A.; Hamidizadeh, Ramin; Kassouf, Wassim; Rendon, Ricardo; Bell, David; Izawa, Jonathan I.; Chin, Joseph L.; Kapoor, Anil; Shayegen, Bobby; Lattouf, Jean‐Baptiste; Saad, Fred; Lacombe, Louis; Fradet, Yves; Fairey, A.S.; Jacobson, Niels-Eric; Drachenberg, Darrel; Cagiannos, Ilias; So, Alan; Black, Peter C.

doi:10.5489/cuaj.5377

Cited by 12 publications

(7 citation statements)

References 26 publications

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“…72 Postoperative recurrences of UTUCs after RNU also commonly occur at bladder (30%) and locoregional (20%), but only 2-6% at contralateral upper tract. 73 Our subgroup analysis showed that AA exposure was associated with 1.949-fold increased risk of intravesical recurrence of UTUC, and 1.477-fold increased risk in patients diagnosed with AAN. It is worth noting that among the three studies reporting contralateral UTUC recurrence, 49,53,56 the recurrence rates of 0-5% in the control groups were similar to that of 2-6% in the general population.…”

Section: Discussionmentioning

confidence: 62%

Aristolochic acid-associated urinary tract cancers: an updated meta-analysis of risk and oncologic outcomes after surgery and systematic review of molecular alterations observed in human studies

Kang

Chen

Lin

et al. 2021

Therapeutic Advances in Drug Safety

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Background: The risk of primary aristolochic acid (AA)-associated urothelial carcinoma (AA-UC) has been summarized by a 2013-published meta-analysis. Given that additional evidence has been continuously reported by original studies, an updated meta-analysis is needed. Meanwhile, to complete the whole picture, a systematic review of molecular alterations observed in AA-urinary tract cancers (AA-UTC) was also performed. Methods: We searched PubMed, Embase and four Chinese databases up to October 2020. Observational studies comparing risk or oncologic outcomes of UTC between patients with and without AA exposure were eligible for systematic review and meta-analysis. Studies investigating molecular alterations in AA-UTC using human tissue samples were eligible for systematic review. Results: In total, 38 and 20 studies were included in the systematic review and meta-analysis, respectively. Exposure to AA led to an overall increased risks of primary UTC [UC and renal cell carcinoma (RCC)] (OR 6.085, 95% CI 3.045–12.160) and postoperatively recurrent UC (RR 1.831, 95% CI 1.528–2.194). Subgroup analysis of postoperative primary AA-upper tract UC (AA-UTUC) showed increased risks of bladder recurrence (adjusted RR 1.949, 95% CI 1.462–2.597) and contralateral UTUC recurrence (crude RR 3.760, 95% CI 2.225–6.353), worse overall survival (adjusted HR 2.025, 95% CI 1.432–2.865) and worse disease-specific survival (adjusted HR 3.061, 95% CI 1.190–7.872), but no effect on cancer-specific survival (adjusted HR 0.772, 95% CI 0.269–2.215). High mutation load with AA mutational signature presenting largely in the putative driver genes was observed in AA-UTUC. In contrast, AA mutational signature is rarely found in the mutated RCC driver genes and the mutation load in AA-RCC is low. Therefore, AA has different roles in the genesis of UTUC and RCC. Conclusions: Implementing effective strategies to completely protect people from exposure to AA is urgently needed. Additionally, more effort should be made in identifying the precise carcinogenic mechanisms of AA to determine the future treatment strategies. Plain language summary Risk, recurrence and survival outcomes after surgery and molecular changes possibly involved in the genesis of aristolochic acid-associated urinary tract cancers Background: The association between aristolochic acid (AA) and primary urothelial carcinoma (UC) has been summarized by a 2013-published meta-analysis. Given that additional evidence has been reported in the past 7 years, an updated meta-analysis is needed. Meanwhile, to complete the whole picture, a systematic review of molecular changes possibly involved in AA-mediated urinary tract carcinogenesis was also performed. Methods: We searched PubMed, Embase and four Chinese databases for human studies up to October 2020. Studies comparing the risk of urinary tract cancer (UTC) between patients with and without AA exposure and studies investigating the molecular changes in AA-associated UTC (AA-UTC) using human tissue samples were eligible for inclusion. Thirty-eight studies were finally included. Results: The results showed that exposure to AA was associated with a 6-fold increased risk of primary UTC (UC and renal cell carcinoma, RCC) and a 1.8-fold increased risk of postoperatively recurrent UC. After studies reporting primary AA-upper tract UC (AA-UTUC) were analyzed, a 1.9-fold increased risk of bladder recurrence and a 3.8-fold increased risk of contralateral UTUC recurrence was observed. Additionally, exposure to AA worsened the postoperative survival of patients with UTUC by a 2-fold increased risk of overall death and a 3-fold increased risk of death from other diseases and recurrences. However, there was no effect on death due to cancer. Lastly, AA seemed to play different roles in the etiology of UTUC and RCC based on the observations of different mutation loads and different distributions of AA-induced mutations in AA-UTUC and AA-RCC samples. Conclusions: Implementing effective strategies to completely protect people from exposure to AA is urgently needed. Moreover, more effort should be made in identifying the precise carcinogenic mechanisms of AA-UTC to determine the future treatment strategies.

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Section: Discussionmentioning

confidence: 62%

Aristolochic acid-associated urinary tract cancers: an updated meta-analysis of risk and oncologic outcomes after surgery and systematic review of molecular alterations observed in human studies

Kang

Chen

Lin

et al. 2021

Therapeutic Advances in Drug Safety

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“…Locoregional or distant recurrence after RNU is not rare and has a high mortality rate once occurred, with limited systemic therapy options available (14). Factors contributing to recurrence are complex and multifocal but include tissue damage, subsequent tumor cell release into the systemic circulation, inflammation, and immune response (19,20).…”

Section: Discussionmentioning

confidence: 99%

“…To date, there is no evidence whether the type of anesthetic technique impacts cancer recurrence or survival in patients with UC of the upper tract (UCUT) undergoing radical nephroureterectomy (RNU). As recurrences after RNU, especially in invasive cases, are not rare, understanding of this association is of clinical importance (14).In this context, we aimed to evaluate cancer recurrence and survival of patients by anesthetic type, utilizing propensity score matching to adjust patient characteristics and minimize preoperative selection bias.…”

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confidence: 99%

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Association Between Anesthetic Technique and Survival After Radical Nephroureterectomy: A Propensity Score-matching Study

Ishiyama

Kondo

Tachibana

et al. 2021

In Vivo

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Background/Aim: Whether anesthesia can affect oncological outcomes in urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy (RNU) is not clear. Patients and Methods: One-hundred an ninetyseven patients who underwent RNU were retrospectively recruited and divided into total intravenous (TIVA, n=90) and volatile inhalation anesthesia (VIA, n=107) groups. A 1:1 propensity score-matching method was employed to minimize selection bias (n=70 each). Cancer-specific (CSS), overall (OS) and metastasis-free (MFS) survival were compared between groups before and after matching. Results: For all survival endpoints, no significant differences were observed between the two study groups, both before (hazard ratio for TIVA: CSS: 0.70, OS: 0.75, MFS: 0.78) and after (hazard ratios for TIV: CSS: 1.21, OS: 0.82, MFS: 0.84) matching. Conclusion: With no survival difference observed according to anesthetic technique for RNU, the choice should be based on factors such as accessibility, prevention of side-effects, or costs.With the growing number of cancer cases, the number of patients undergoing surgery under general anesthesia is also increasing (1). In recent years, hypotheses have emerged that the anesthetic technique during surgery may impact cancer recurrence or survival. Proposed mechanisms involve the characteristics of agents used in volatile inhalation anesthesia (VIA) and total intravenous anesthesia (TIVA). According to previous studies, VIA agents can impair immune function enabling tumor cells to evade natural killer cells (2) and can up-regulate signaling pathways such as the hypoxia-inducible factor 1-alpha (HIF1α) pathway, thereby promoting the proliferation of residual tumors (3). By contrast, propofol used in TIVA may protect from cancer recurrence through its antiinflammatory and antioxidant potentials (4, 5).However, the clinical evidence on this topic remains conflicting. Wigmore et al. reported based on a dataset of mixed malignancy types that the use of TIVA is associated with a lower overall risk of death compared to VIA (6). Several publications found similar results (7-9), but other studies showed no benefit of TIVA over VIA (10)(11)(12). For urothelial carcinoma (UC), Pfail et al. demonstrated that VIA is associated with an increased risk of recurrence compared to TIVA during robot-assisted radical cystectomy for bladder cancer (13). To date, there is no evidence whether the type of anesthetic technique impacts cancer recurrence or survival in patients with UC of the upper tract (UCUT) undergoing radical nephroureterectomy (RNU). As recurrences after RNU, especially in invasive cases, are not rare, understanding of this association is of clinical importance (14).In this context, we aimed to evaluate cancer recurrence and survival of patients by anesthetic type, utilizing propensity score matching to adjust patient characteristics and minimize preoperative selection bias. Patients and MethodsPatient selection and data collection. This retrospective study included 224 consecutiv...

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“…While little is known about the outcomes of these patients, it may be reasonable to follow existing guidelines for high-risk UTUC. 5 …”

Section: Discussionmentioning

confidence: 99%

Development of secondary urothelial carcinoma following complete response to immune checkpoint inhibitors

Lavoie¹,

Vandekerkhove

Murtha

et al. 2021

Urology Case Reports

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The management of metastatic urothelial cancer is rapidly evolving since immune checkpoint inhibitors were introduced. We present the case of a patient with metastatic upper tract urothelial cancer who had a complete response to durvalumab and tremelimumab. This patient then developed multiple non-invasive papillary bladder tumours. Next-generation sequencing revealed that the tumours shared ancestry with the upper tract cancer, although there were key differences, most notably the presence of a TP53 missense mutation in the upper tract disease that was absent in the bladder tumours. This illustrates an important practice point in the management of exceptional responders to checkpoint inhibitors.

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Surveillance guidelines based on recurrence patterns for upper tract urothelial carcinoma

Cited by 12 publications

References 26 publications

Aristolochic acid-associated urinary tract cancers: an updated meta-analysis of risk and oncologic outcomes after surgery and systematic review of molecular alterations observed in human studies

Aristolochic acid-associated urinary tract cancers: an updated meta-analysis of risk and oncologic outcomes after surgery and systematic review of molecular alterations observed in human studies

Association Between Anesthetic Technique and Survival After Radical Nephroureterectomy: A Propensity Score-matching Study

Development of secondary urothelial carcinoma following complete response to immune checkpoint inhibitors

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