Impact of Salvage Cytotoxic Chemotherapy on Prognosis in Patients with Recurrence After Radical Cystectomy: A Multi-Institutional Retrospective Study

Background In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients. Methods In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient’s performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS). Results Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR]: 2.13; 95% confidence interval [CI]: 1.17 to 3.85; P = 0.01) and locally advanced disease at RC (HR: 1.92; 95% CI: 1.06 to 3.46; P = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1–2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy. Conclusions The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.

Risk Factors and Diagnosis of Advanced Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer affecting humans. The combination of the increasing incidence and high mortality in advanced stages of the disease, defines cSCC as an emerging public health problem. Advanced disease includes metastatic and locally advanced cSCC. Metastatic disease refers to the presence of locoregional metastasis (in transit or to regional lymph nodes) or distant metastasis. Locally advanced disease has been defined as non-metastatic cSCC that is unlikely to be cured with surgery, radiotherapy, or combination treatment. While metastatic cSCC is easily diagnosed, locally advanced disease lacks consensus definition and diagnosis is made after multidisciplinary board consultation. Identifying patients with aggressive cSCC at highest risk for relapse may prevent the occurrence of advanced disease. Prognostic factors suggested by most guidelines include tumor diameter (>2 cm), localization on temple/ear/lip/area, thickness (>6 mm), or invasion beyond subcutaneous fat, poor grade of differentiation, desmoplasia, perineural invasion, bone erosion, immunosuppression, undefined borders, recurrence, growth rate, site of prior radiotherapy, and lymphatic or vascular involvement. Although risk factors associated with worse outcomes are well known, there is still a gap of knowledge on the precise risk of each factor taken individually. The aim of this review is to summarize cSCC prognostic factors and encompass the various staging systems to guide management and follow-up in cSCC patients at higher risk for local recurrence and metastasis. Finally, we describe the hallmarks of the advanced disease. Advanced cSCC diagnosis should be made by a multidisciplinary board considering patients’ performance status and disease characteristics

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

Clinicopathological and genomic features in patients with head and neck neuroendocrine carcinoma

Neuroendocrine carcinoma (NEC) of the head and neck is a rare type of malignancy, accounting for only 0.3% of all head and neck cancers, and its clinicopathological and genomic features have not been fully characterized. We conducted a retrospective analysis of 27 patients with poorly differentiated NEC of the head and neck seen at our institution over a period of 15 years. Patient characteristics, adopted therapies, and clinical outcomes were reviewed based on the medical records. Pathological analysis and targeted sequencing of 523 cancer-related genes were performed using evaluable biopsied/resected specimens based on the clinical data. The most common tumor locations were the paranasal sinus (33%) and the oropharynx (19%). Eighty-one percent of the patients had locally advanced disease. The 3-year overall survival rates in all patients and in the 17 patients with locally advanced disease who received multimodal curative treatments were 39% and 53%, respectively. Histologically, large cell neuroendocrine carcinoma was the predominant subtype (58% of evaluable cases), and the Ki-67 labeling index ranged from 59 to 99% (median: 85%). Next-generation sequencing in 14 patients identified pathogenic/likely pathogenic variants in TP53, RB1, PIK3CA-related genes (PREX2, PIK3CA, and PTEN), NOTCH1, and SMARCA4 in six (43%), three (21%), two (14%), two (14%), and one (7%) patients, respectively. Sequencing also detected the FGFR3-TACC3 fusion gene in one patient. The median value of the total mutational burden (TMB) was 7.1/Mb, and three patients had TMB ≥ 10. Regardless of the aggressive pathological features, our data revealed favorable clinical characteristics in the patients with locally advanced disease who received curative treatment. The lower TP53 and RB1 mutation prevalence rates compared to those described for small cell lung cancer suggests the biological heterogeneity of NEC in different parts of the body. Furthermore, the FGFR3-TACC3 fusion gene and mutations in genes encoding the components of the NOTCH and PI3K/AKT/mTOR pathways found in our study may be promising targets for NEC of the head and neck.

The age threshold of the 8th edition AJCC classification is useful for indicating patients with aggressive papillary thyroid cancer in clinical practice

Background Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC. Methods We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n = 523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients < 45 (n = 193) vs. ≥45 (n = 330) were compared, and in the second series (cut off 55) patients < 55 (n = 306) vs. ≥55 (n = 217) were compared. Results The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p = 0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3 + T4 (OR = 4.87) and presence of LNM (N1) (OR = 3.78) was observed in ≥45 years old group (p = 0.021 and p < 0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3 + T4) was higher (OR = 5.21) and LNM presence was OR = 4.76 (p < 0.001 and p < 0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p < 0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals. Conclusions The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice.

Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice.

Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.