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Objective: To compare in a phase III trial the efficacy and safety of nanoparticle albumin‐bound (nab)‐paclitaxel plus gemcitabine (GA) with that of carboplatin plus gemcitabine (GCb) as a first‐line treatment for patients with cisplatin‐ineligible metastatic urothelial cancer (mUC). Patients and Methods: Treatment‐naive, cisplatin‐ineligible patients with mUC were assigned randomly to either the GA (both nab‐paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on Days 1 and 8, every 21 days) or GCb group (carboplatin area under the free carboplatin plasma concentration versus time curve of 4.5 on Day 1, gemcitabine 1000 mg/m2 on Days 1 and 8, every 21 days). The primary endpoint was progression‐free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and patient‐reported outcomes (PROs). Results: The trial was terminated early because of slow accrual after 54 patients were enrolled: 26 in in the GA group and 28 in the GCb groups. The median PFS was 6.7 vs 5.9 months for the GA and GCb groups, respectively (P = 0.248). The median OS time was 12.1 vs 10.7 months for the GA and GCb groups, respectively (P = 0.837). The ORR and DCR were 40% vs 46.4% (P = 0.637) and 72% vs 68% (P = 0.188) in the GA and GCb groups, respectively. Patients treated with GA showed significantly lower incidence of Grade 3–4 thrombocytopenia and does reduction and delay. Although peripheral sensory neuropathy was higher in the GA arm, no Grade 3 neuropathy occurred. There was no difference in the PROs between the two groups. Conclusion: While not powered for comparison, first‐line GA showed similar efficacy and better tolerability and might be considered a rational alternative to GCb. [ABSTRACT FROM AUTHOR]

Background: Lymph node characteristics markedly affect nasopharyngeal carcinoma (NPC) prognosis. Matted node (MN), an important characteristic for lymph node, lacks explored MRI‐based prognostic implications. Purpose: Investigate MRI‐determined MNs' prognostic value in NPC, including 5‐year overall survival (OS), distant metastasis‐free survival (DMFS), local recurrence‐free survival (LRFS), progression‐free survival (PFS), and its role in induction chemotherapy (IC). Study Type: Retrospective cohort survival study. Population: Seven hundred ninety‐two patients with non‐metastatic NPC (female: 27.3%, >45‐year old: 50.1%) confirmed by biopsy. Field Strength/Sequence: 5‐T/3.0‐T, T1‐, T2‐ and post‐contrast T1‐weighted fast spin echo sequences acquired. Assessment: MNs were defined as ≥3 nodes abutting with intervening fat plane replaced by extracapsular nodal spread (ENS). Patients were observed every 3 months for 2 years and every 6 months for 5 years using MRI. Follow‐up extended from treatment initiation to death or final follow‐up. MNs were evaluated by three radiologists with inter‐reader reliability calculated. A 1:1 matched‐pair method compared survival differences between MN‐positive patients with or without IC. Primary endpoints (OS, DMFS, LRFS, PFS) were calculated from therapy initiation to respective event. Statistical Tests: Kappa values assessed inter‐reader reliability. Correlation between MN, ENS, and LNN was studied through Spearman's correlation coefficient. Clinical characteristics were calculated via Fisher's exact, Chi‐squared, and Student's t‐test. Kaplan–Meier curves and log‐rank tests analyzed all time‐to‐event data. Confounding factors were included in Multivariable Cox proportional hazard models to identify independent prognostic factors. P‐values <0.05 were considered statistically significant. Results: MNs incidence was 24.6%. MNs independently associated with decreased 5‐year OS, DMFS, and PFS; not LRFS (P = 0.252). MN‐positive patients gained significant survival benefit from IC in 5‐year OS (88.4% vs. 66.0%) and PFS (76.4% vs. 53.5%), but not DMFS (83.1% vs. 69.9%, P = 0.145) or LRFS (89.9% vs. 77.8%, P = 0.140). Data Conclusion: MNs may independently stratify NPC risk and offer survival benefit from IC. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)‐associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor–based combination therapy (PCT). Methods: HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS) in the HPV+ and HPV– groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC. Results: Among patients receiving first‐line PCT, ORR (91.7% vs. 64.6%, p =.014) and DCR (100.0% vs. 79.2%, p =.025) in the HPV+ group were higher compared to the HPV– group. Kaplan–Meier curves demonstrated that the HPV+ group exhibited superior PFS (p =.005) and OS (p =.004) for patients in the first‐line setting. However, these advantages of HPV infection were not observed in multi‐line PCT (p >.050). HPV status remained an independent prognostic factor for predicting better ORR (p =.024), PFS (p =.002), and OS (p =.020) in the multivariate analyses. Landmark analyses showed that the HPV‐induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune‐activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues. Conclusions: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first‐line PCT because of the possible stimulation of the antitumor immune microenvironment. Plain Language Summary: Human papillomavirus (HPV) infection may induce better objective response rate, progression‐free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first‐line programmed cell death protein 1 inhibitor–based combination therapy (PCT) instead of multi‐line PCT.HPV infection‐induced PFS advantage occurs at an early stage (within 3 months) whereas OS superiority occurs at a relatively late stage (within 9 months).Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues. Human papillomavirus (HPV) infection may result in improved treatment efficacy and disease prognosis in patients with advanced penile squamous cell carcinoma (PSCC) receiving first‐line programmed cell death protein 1 inhibitor–based combination therapy. The antitumor immune microenvironment is stimulated by HPV infection in advanced PSCC tissues. [ABSTRACT FROM AUTHOR]

Background: Metastatic lymph nodal number (LNN) is associated with the survival of nasopharyngeal carcinoma (NPC); however, counting multiple nodes is cumbersome. Purpose: To explore LNN threshold and evaluate its use in risk stratification and induction chemotherapy (IC) indication. Study Type: Retrospective. Population: A total of 792 radiotherapy‐treated NPC patients (N classification: N0 182, N1 438, N2 113, N3 59; training group: 396, validation group: 396; receiving IC: 390). Field Strength/Sequence: T1‐, T2‐ and postcontrast T1‐weighted fast spin echo MRI at 1.5 or 3.0 T. Assessment: Nomogram with (model B) or without (model A) LNN was constructed to evaluate the 5‐year overall (OS), distant metastasis‐free (DMFS), and progression‐free survival (PFS) for the group as a whole and N1 stage subgroup. High‐ and low‐risk groups were divided (above vs below LNN‐ or model B‐threshold); their response to IC was evaluated among advanced patients in stage III/IV. Statistical Tests: Maximally selected rank, univariate and multivariable Cox analysis identified the optimal LNN threshold and other variables. Harrell's concordance index (C‐index) and 2‐fold cross‐validation evaluated discriminative ability of models. Matched‐pair analysis compared survival outcomes of adding IC or not. A P value < 0.05 was considered statistically significant. Results: Median follow‐up duration was 62.1 months. LNN ≥ 4 was independently associated with decreased 5‐year DMFS, OS, and PFS in entire patients or N1 subgroup. Compared to model A, model B (adding LNN, LNN ≥ 4 vs <4) presented superior C‐indexes in the training (0.755 vs 0.727) and validation groups (0.676 vs 0.642) for discriminating DMFS. High‐risk patients benefited from IC with improved post‐IC response and OS, but low‐risk patients did not (P = 0.785 and 0.690, respectively). Conclusions: LNN ≥ 4 is an independent risk stratification factor of worse survival in entire or N1 staging NPC patients. LNN ≥ 4 or the associated nomogram has potential to identify high‐risk patients requiring IC. Evidence Level: 4 Technical Efficacy: 4 [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the anti‐tumour activity and safety of anti‐programmed death receptor‐1 (PD‐1) antibody plus epidermal growth factor receptor blockade combined with platinum‐based chemotherapy (PEP) as first‐line therapy for stage IV penile squamous cell carcinoma (PSCC). Patients and Methods: We conducted a retrospective review of 17 patients with stage IV PSCC undergoing first‐line PEP at Sun Yat‐sen University Cancer Center between January 2018 and September 2021. Clinical responses were assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events version 5.0. Results: Of 17 patients who received first‐line PEP, 13 were observed to have partial responses. Twelve patients subsequently received consolidated surgery. Nine of these achieved pN0 status, of whom six with locally advanced PSCC achieved pathological complete response. The median (range) follow‐up time was 24.87 (3.63–29.40) months. Median PFS and median OS were not reached, with 2‐year PFS and OS rates being 68.4% (95% confidence interval [CI] 48.7–96.1) and 62.9% (95% CI 41.6–95), respectively. Eight patients experienced Grade 3 or 4 treatment‐related AEs. No Grade 5 AEs or death associated with treatment was observed. Conclusions: Anti‐PD‐1 antibody plus epidermal growth factor receptor blockade and platinum‐based chemotherapy showed promising anti‐tumour activity, acceptable toxicity, and satisfying long‐term survival for stage IV PSCC. Larger clinical trials are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Nodal (N) stage is one of the most important predictors for distant metastasis in nasopharyngeal carcinoma (NPC) patients. It may ignore potentially useful nodal features, such as nodal matting (three or more lymph nodes abutting together with the absence of intervening fat planes). Purpose: To explore the prognostic value of nodal matting in NPC patients and construct a nomogram with nodal matting for predicting distant metastasis‐free survival (DMFS). Study type: Retrospective. Population: In all, 792 NPC patients treated with intensity modulated radiation therapy from 2010 to 2013 were enrolled with 2:1 training (n = 527) and validation (n = 65) cohorts. Field Strength/Sequence: T1‐ and T2‐weighted imaging at 1.5 or 3.0T. Assessment: Nodal matting and other nodal characteristics were assessed with MRI. MR images were evaluated separately by three radiologists. The association between nodal matting and DMFS was analyzed. Statistical Tests: Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Nomograms were constructed from a multivariate logistic regression model with and without nodal matting. The predictive accuracy and discriminative ability of the nomograms were determined by concordance index (C‐index) and calibration curves. The results were validated using bootstrap resampling and validation cohort. Results: The incidence of nodal matting was 24.6% (195/792) in all patients. In the training cohort, nodal matting was independently associated with DMFS (hazard ratio [HR] = 1.97 [1.05–3.69], P < 0.05). N1 patients with nodal matting had worse DMFS than N1 patients without (P < 0.05). However, no significant difference was observed when comparing N1 patients with nodal matting to N2 patients (P = 0.464). The C‐index of the nomogram with nodal matting was higher than the nomogram without (0.717 vs. 0.699, P = 0.084). Data Conclusion: Nodal matting was an independent prognostic factor for DMFS in NPC patients. It may help to select patients at high risk of distant metastasis. [ABSTRACT FROM AUTHOR]