Detecting undetectable - epidemiology, etiology, and diagnosis of carcinoma of unknown primary - systematic review.

Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of oncologic patients, but the survival time varies from 6 weeks to 5 months. The diagnostics should begin with a clinical evaluation and basic laboratory tests. For CUP placed in head and neck the positron emission tomography - computed tomography is recommended; pancreatic or lung neoplasms are diagnosed with the computed tomography as well. Recently, the magnetic resonance, especially whole-body diffusion-weighted imaging has been introduced to the imaging panel. The lesion obtained during surgically removed metastases or biopsy material should be histopathological and molecularly examined to define the type of tumor. The basic immunoexpression panel should include cytokeratin-5/6, -7 and -20, EMA, synaptophysin, chromogranin, vimentin and GATA3 and molecular expression of ERBB2, PIK3CA, NF1, NF2, BRAF, IDH1, PTEN, FGFR2, EGFR, MET and CDK6. During the accurate diagnostics enable to classify malignancy of undefined primary origin as provisional CUP or finally confirmed CUP in which the primary place of tumor remains undetectable. The detailed diagnostics should be performed in highly specified centers to establish an accurate diagnosis and to initiate personalized treatment. Majority of patients are diagnosed with adenocarcinoma (70%), undifferentiated carcinoma (20%), squamous cell or transitional cell/uroepithelial carcinoma (5-10%), neuroendocrine tumor (5%) and with minor incidence other histological types, including melanoma.

Prognostic Factors for Distal Bile Duct Carcinoma After Surgery.

BACKGROUND: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases.

OBJECTIVE: Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T cell and chimeric antigen receptor T (CAR-T) cell antitumour function in CRLM slice cultures. DESIGN: We created organotypic slice cultures from human CRLM (n=38 patients' tumours) and tested the antitumour effects of a neutralising antibody against IL-10 (αIL-10) both alone as treatment and in combination with exogenously administered carcinoembryonic antigen (CEA)-specific CAR-T cells. We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridisation, single-cell RNA sequencing, reverse-phase protein arrays and time-lapse fluorescent microscopy. RESULTS: αIL-10 generated a 1.8-fold increase in T cell-mediated carcinoma cell death in human CRLM slice cultures. αIL-10 significantly increased proportions of CD8+ T cells without exhaustion transcription changes, and increased human leukocyte antigen - DR isotype (HLA-DR) expression of macrophages. The antitumour effects of αIL-10 were reversed by major histocompatibility complex class I or II (MHC-I or MHC-II) blockade, confirming the essential role of antigen presenting cells. Interrupting IL-10 signalling also rescued murine CAR-T cell proliferation and cytotoxicity from myeloid cell-mediated immunosuppression. In human CRLM slices, αIL-10 increased CEA-specific CAR-T cell activation and CAR-T cell-mediated cytotoxicity, with nearly 70% carcinoma cell apoptosis across multiple human tumours. Pretreatment with an IL-10 receptor blocking antibody also potentiated CAR-T function. CONCLUSION: Neutralising the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.

Distant metastasis without regional progression in non-muscle invasive bladder cancer: case report and pooled analysis of literature.

BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) represents the majority of bladder neoplasms. It is unusual for NMIBC metastasizing distantly without regional progression, namely metastatic NMIBC (mNMIBC), which is still poorly understood and easily omitted based on current management policies. So far, description of mNMIBC is limited to a few case reports. METHODS: We reported a 70-year-old man with NMIBC who suffered from cervical metastasis without pelvic recurrence at 41 months after initial diagnosis. Then we performed a collective analysis of this case together with published mNMIBC cases searched from PubMed, Embase, and Web of Science, aiming to illustrate baseline clinicopathologic parameters, metastatic patterns, and treatment outcomes of these patients and analyze associated influencing factors. RESULTS: After scrupulous review, 45 cases previous reported and the one from our center were incorporated into the aggregated cohort of mNMIBC, including 34 males and 12 females. Primary tumors from 46.7% of patients were high-grade (HG) or grade 3 (G3) and 65.1% had T1 lesions. Aberrant biomarker expression was found in tumors of some cases. Most (40/46) metastases of mNMIBC occurred at a single site, mainly in lung, bone and lymph nodes. Apart from three cases of de novo mNMIBC, the mean metastasis-free survival (MFS) interval of metachronous mNMIBC was 42.5 months, which was obviously longer than conventional metastatic bladder cancer. Shortened MFS interval was associated with old age, T1 or HG/G3 primary tumors, and non-lung metastases. Systemic chemotherapy and metastasectomy or radiotherapy for oligometastatic lesion were main therapeutic approaches of mNMIBC, and immunotherapy was adopted for the case from our center. Lung and bone metastases correlated with relatively favorable and unfavorable survival outcomes, respectively. Compared with monotherapy, chemotherapy, or immunotherapy combined with local cytoreduction got more favorable outcomes. CONCLUSION: Although rare, mNMIBC occurs more in tumors with high-risk features. Usually, mNMIBC metastasizes later than conventional metastatic bladder cancer and manifests as solitary lesion. Outcomes of mNMIBC would be influenced by metastatic site and post-metastatic treatment. Systemic treatment combined with local cytoreduction may render survival benefit in selected patients.

Metastatic cancer along ancient Silk Road: A possible case from Xinjiang (China).

OBJECTIVE: Palaeopathological evidence of cancer, especially metastatic cancer, is rare in China. This paper describes and diagnoses a cranium with multiple lytic lesions recovered from the Sampula cemetery in Xinjiang, attempting to diagnose the type of disease that could have caused the pathological lesions observed. MATERIAL: A cranium from an adult male (#00106) was recovered from the Sampula cemetery (dated to 55 BCE to 335 CE) located in the Luopu County, the Hotan River oasis on the southern edge of the Tarim Basin in southern Xinjiang. METHODS: The cranium was assessed macroscopically and radiographically (CT). RESULTS: Multiple osteolytic lesions with irregular and "moth-eaten" margins were detected in cranium #00106. CT scans revealed the development of the lesions began at the diploe and identified a "button sequestrum". CONCLUSIONS: Based on lesion characteristics, metastatic carcinoma was likely the cause of lesions found in cranium #00106. SIGNIFICANCE: This case has expanded our knowledge of the malignant neoplasms of ancient populations in northwest China and discusses the possible risk factors in the occurrence of cancer in the Sampula site, as well as the possible impacts of skeletal metastases on the individual. LIMITATIONS: The distribution of osteolytic lesions over the complete skeleton cannot be observed because of the unavailability of postcranial bone. SUGGESTIONS FOR FUTURE RESEARCH: With the increasing number of reports describing diseases in ancient China, the patterns of diseases occurrence and development can be further explored from spatial and temporal perspectives.

Pulmonary lymphangitis sarcomatosis: a rare cause of severe progressive dyspnoea.

Pulmonary lymphangitis carcinomatosis is a complication of malignancy with a poor prognosis. We describe an unusual case in which it caused ventilatory failure and unfortunately death in a previously well male in his 70s. Abnormal chest imaging led to a wide differential diagnosis with Bronchoscopy confirming malignant cells. MRI of his pelvis and biopsy was done diagnosis of metastatic leiomyosarcoma, a particularly aggressive malignancy. Sarcoma-related lymphangitis carcinomatosis is rarely described in the literature and this is the first case to our knowledge of its association with leiomyosarcoma.

Indications and outcomes of palliative major amputation in patients with metastatic cancer.

BACKGROUND: Patients with stage IV cancer often experience diminished quality of life and pain. Although palliative amputation (PA) can reduce pain, it is infrequently performed because of the morbidity associated with amputation and the limited life expectancy in this population. Here, we describe the indications for PA in patients with stage IV carcinoma or sarcoma and discuss their clinical courses and outcomes. We hypothesized that PA would be associated with reduced pain and improved quality of life in these patients. METHODS: We retrospectively reviewed medical records of all patients who underwent major amputation (proximal to the ankle or wrist) for metastatic sarcoma or carcinoma from January 1995 to April 2021. We excluded patients who underwent amputation for indications other than palliation. Cox proportional hazards regression analysis was used to determine factors associated with survival after PA. RESULTS: Twenty-six patients underwent PA (11 for carcinoma, 15 for sarcoma). The most common indications for PA were pain (all patients) and fungating tumor (16 patients). PA was the initial surgery in 7 patients. Forequarter amputations were the most common procedure (6 patients). All patients reported reduced pain after PA, with the mean (±standard deviation) visual analog pain score (on a 10-point scale) decreasing from 5.7 ± 2.9 preoperatively to 0.43 ± 1.3 postoperatively (p < 0.001). The mean preoperative ECOG score was 1.9 ± 0.2 compared with 1.3 ± 0.1 postoperatively (p < 0.001). Fourteen patients were fitted for prostheses (6 upper extremity, 8 lower extremity). Two patients had local recurrence, both within 6 months after PA. The mean survival time after PA was 13 ± 12 months, and mean follow-up was 28 ± 29 months. Mean survival time after PA was not significantly different between patients with sarcoma (11 ± 11 months) versus carcinoma (15 ± 14 months) (p = 0.51). Adjuvant chemotherapy was positively associated with survival; no other factors were associated with survival. CONCLUSIONS: PA was associated with significantly reduced pain in all patients with stage IV cancer. PA should be considered for those with intractable pain, fungating tumors, or symptoms that diminish quality of life. LEVEL OF EVIDENCE: Level III.

A 33-Year-Old Man With Chest Pain.

CASE PRESENTATION: A 33-year-old man was admitted with a 4-week history of intermittent, right-sided chest pain. Two weeks before the incident, he had completed a 10-day course of levofloxacin for a presumed right-sided pneumonia without much improvement. He denied any dyspnea, cough, sputum production, hemoptysis, night sweats, or weight loss. He was an active smoker with a 20-pack-year smoking history and 1-year history of vaping nicotine.

Cystic hypersecretory carcinoma with invasion: Case series on a rare variant of carcinoma breast.

BACKGROUND: Cystic Hypersecretory Carcinoma (CHC) is a rare subset of breast carcinoma. It is part of a spectrum of cystic hypersecretory lesions which includes cystic hypersecretory hyperplasia (CHH), CHH with atypia, CHC in situ and CHC with invasion. Approximately 65 cases of cystic hypersecretory lesions have been reported; most of them were CHC in situ and only 19 cases of CHC with invasion have been reported so far. CASE PRESENTATION: We are reporting 2 cases of 47 and 62 year old women with a palpable breast mass for 6 and 1 month duration respectively. Trucut biopsy was carried out for both which showed high grade ductal carcinoma in situ with microinvasion in the first patient and the latter showed a tiny focus of invasive carcinoma. Simple mastectomy and modified radical mastectomy (MRM) were done for the respective cases; both showed dilated cystic spaces filled with eosinophilic secretions (thyroid colloid-like), lining neoplastic cells that showed variable degrees of proliferation, atypia and in situ carcinoma. There were foci of invasion in both cases and hence a morphological diagnosis of CHC with invasion was made. CONCLUSION: Owing to a smaller number of reported cases, little is known about the biological behavior, prognosis and molecular profile of cystic hypersecretory carcinoma.

Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).

BACKGROUND AND OBJECTIVES: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

Nationwide oncological networks for resection of colorectal liver metastases in the Netherlands: Differences and postoperative outcomes.

INTRODUCTION: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. METHODS: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. RESULTS: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. CONCLUSION: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued.

Cost-effectiveness analysis of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with gastric cancer and peritoneal metastasis.

OBJECTIVE: The aim of this study was to assess the cost-effectiveness of pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) for the treatment of advanced gastric cancer. METHODS: A Partitioned Survival Model followed by state transition Markov model was developed to estimate the costs and effectiveness of the use of PIPAC C/D versus palliative chemotherapy in the UK. The intervention was assessed at two different levels of care, including upfront therapy (PIPAC C/D plus Oxaliplatin in combination with Capecitabine (XELOX) chemotherapy versus first-line chemotherapy alone) and second-line therapy (PIPAC C/D alone versus second-line chemotherapy (ramucirumab monotherapy)). Data from multiple sources, including published literature and UK-based databases, were used to inform the economic model. RESULTS: For the upfront therapy analysis, the estimated total costs in the intervention and comparator arms were £32,606 (SD: £3877) and £17,844 (SD: £920), respectively. PIPAC C/D plus XELOX led to an increase of 0.46 in quality-adjusted life-years (QALYs) gained. The incremental cost per QALY gained was £31,868. For the second-line therapy analysis, the use of PIPAC C/D led to an increase of 0.19 in QALYs and a £21,474 reduction in costs, meaning the intervention was a dominant strategy. CONCLUSIONS: The cost-effectiveness results for the upfront therapy analysis indicate that PIPAC C/D plus chemotherapy is a cost-effective strategy. Additionally, PIPAC C/D alone as a second-line therapy has the potential to reduce costs and improve clinical outcomes for patients with advanced gastric cancer with peritoneal metastasis.

Long-term prognosis of patients with cancer-related genes detected in postoperative peritoneal washings obtained during curative gastrectomy.

BACKGROUND: Cancer cells in intraoperative peritoneal washings (PW) indicate increased peritoneal recurrence. Detection of CEA or CK20 genes indicates poor prognosis. We assessed long-term prognosis of patients with amplification of cancer-related genes in PW obtained intraoperatively during curative gastric cancer surgery. METHODS: PW was collected before and immediately after curative gastrectomy. CEA, CK20, TFF1, MUC2, and FABP1-mRNA were selected as marker genes for reverse transcription polymerase chain reaction. Peritoneal recurrence-free survival (PRFS) and overall survival (OS) after >7-year follow-up were examined using the Kaplan-Meier method. RESULTS: Of 138 patients who underwent gastrectomy with negative cytological findings at laparotomy, 80 patients showed negative cancer-related gene amplification in preoperative PW. Fifty-eight patients were excluded due to positive gene amplification, which suggested presence of preoperative peritoneal cancer cells. The 80 patients had mRNA amplification in PW after surgery. Amplification of multiple and single cancer-related marker genes was observed in 38 and 21 patients; 21 cases had marker-negative results. Five-year PRFS was 69.1%, 95.2%, and 100% in multi-marker-positive, single marker-positive, and marker-negative cases, respectively. Multi-marker-positive patients had significantly worse PRFS than the other groups (p < 0.05). Multivariate analysis in the Cox proportional hazards model identified multi-marker-positivity as an independent prognostic factor for PRFS (hazard ratio, 7.6; 95% confidence interval, 1.07-62.63; p = 0.046), and multi-marker-positive patients had significantly worse OS than other groups (p < 0.01). CONCLUSION: Multi-marker cancer-related gene amplification in PW is associated with worse prognosis in PRFS and OS even after a long follow-up; PRFS can be stratified by the number of genes amplified.

The impact of additional margin coagulation with radiofrequency in liver resections with subcentimetric margin: can we improve the oncological results? A propensity score matching study.

BACKGROUND: Whereas the usefulness of radiofrequency (RF) energy as haemostatic method in liver surgery has become well established in the last decades, its intentional application on resection margins with the aim of reducing local recurrence is still debatable. Our goal was to compare the impact of an additional application of RF energy on the top of the resection surface, namely additional margin coagulation (AMC), on local recurrence (LR) when subjected to a subcentimeter margin. METHODS: We retrospectively analyzed 185 patients out of a whole cohort of 283 patients who underwent radical hepatic resection with subcentimetric margin. After propensity score adjustment, patients were classified into two balanced groups according to whether RF was applied or not. RESULTS: No significant differences were observed within groups in baseline characteristics after PSM adjustment. The LR rate was significantly higher in the Control than AMC Group: 12 patients (14.5%) vs. 4 patients (4.8%) (p = 0.039). The estimated 1, 3, and 5-year LR-free survival rates of patients in the Control and AMC Group were: 93.5%, 86.0%, 81.0% and 98.8%, 97.2%, 91.9%, respectively (p = 0.049). Univariate Cox analyses indicated that the use of the RF applicator was significantly associated with lower LR (HR = 0.29, 95% confidence interval 0.093-0.906, p = 0.033). The Control Group showed smaller coagulation widths than the AMC group (p < 0.001). CONCLUSIONS: An additional application of RF on the top of the resection surface is associated with less local hepatic recurrence than the use of conventional techniques.

The pattern of peritoneal colorectal metastasis predicts survival after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND: Peritoneal cancer index (PCI) has been used reliably to prognosticate patients with peritoneal metastasis, however, it fails to describe the patterns of peritoneal spread and to correlate these patterns to survival outcomes. We aim to define the scattered peritoneal spread (SPS) as a pattern associated with worse survival in colorectal peritoneal metastasis. METHODS: A retrospective analysis of metastatic colorectal cancer patients from a prospectively maintained database of peritoneal surface malignances (n = 280) between 2015 and 2020. SPS was defined by the presence of at least two distant and non-contiguous PCI regions. We compared patients with SPS (n = 73) and clustered peritoneal spread (CPS) (n = 88) for demographics, perioperative and survival outcomes. RESULTS: No difference in demographics or post-operative course was noted between the groups. The median follow-up was 15.4 months (0.4-70.8 months). Worse disease-free survival (DFS) in the SPS group with an estimated median of 8.2 months compared to 22.5 months in the CPS spread group, (p = 0.001). The estimated median overall survival (OS) for SPS group was 35.7 months whereas in the CPS group the median was not reached (p = 0.025). The same effect of SPS was preserved even after stratification of PCI. CONCLUSIONS: We defined and described the association of the peritoneal spread pattern to survival outcomes. SPS patients exhibit worse DFS and OS independent of the PCI level. Integration of malignant spread pattern into prognostication models along with PCI may aid in predicting oncological outcomes.

The impact of postoperative complications following cytoreductive surgery combined with oxaliplatin based heated intraperitoneal chemotherapy.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has become the mainstream treatment for peritoneal metastases of colorectal origin. This extensive treatment is known for its increased morbidity rate. In this study, the impact of postoperative complications on survival was evaluated in a high-volume centre. PATIENTS AND METHOD: Between November 2016 through October 2018, all 106 patients with peritoneal metastases of colorectal origin treated with CRS + HIPEC with oxaliplatin were evaluated. Data on patient characteristics, Peritoneal Carcinomatosis Index (PCI), operative procedure, post-operative complications (Clavien-Dindo classification grade III or higher) and survival were collected. In-hospital postoperative complications were analysed for their association with patient characteristics, tumour load (PCI), and operative procedure with logistic regression analyses. Survival was analysed with the Cox regression analysis. RESULTS: Of 106 patients, 78% had an un-eventful in-hospital recovery. Of those patients who experienced complications, 52% patients had one complication and 48% had more than one. The median follow-up time was 33.8 months. Median survival was 22.4 months (95% CI 12.2-NR) for patients who experienced complications and not reached for those who did not. Survival was significantly associated with complications (HR 2.2, 95% CI 1.2-4.0) as well as with PCI (HR 1.1, 95% CI 1.1-1.2) in univariate analyses. A stepwise Cox regression analysis showed both PCI and complications had an independent negative impact on survival. CONCLUSION: Postoperative complications, independently of tumour load, led to reduced survival in patients with peritoneal metastases of colorectal origin when treated with CRS + HIPEC with oxaliplatin.

Survival Prediction by Baseline Systemic Immune-inflammation Index (SII) and its Changes During First-line Platinum-based Treatment in a Caucasian Population of Patients With Metastatic Urothelial Carcinoma (MUC).

BACKGROUND/AIM: Systemic immune-inflammation index (SII) predicts survival of patients with various malignancies. This study explored the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects. PATIENTS AND METHODS: We evaluated 181 consecutive MUC patients treated with first-line platinum-based therapy. Karnofsky performance status <80% and visceral metastasis were present in 18.2% and 46.4% of patients, respectively. SII was based on platelet × neutrophil/lymphocyte counts. Study population was dichotomized by median into high and low SII groups before the initiation of chemotherapy and at week 6. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: At median follow-up of 9.6 months, 174 patients experienced disease progression and 173 died. Patients with low SII at baseline and at week 6 had significantly better PFS (HR=0.58; p=0.0002 and HR=0.55; p<0.0001) and OS (HR=0.54; p<0.0001 and HR=0.54; p<0.0001) compared to patients with high SII. Independent prognostic value of SII was confirmed in a multivariate analysis. CONCLUSION: High SII before chemotherapy that persists at week 6 negatively affects survival. SII at baseline can be used in the stratification of patients within clinical trials and in clinical practice.