The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112-7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.

Cancer spread beyond the prostate, including extraprostatic extension (other than seminal vesicle or bladder invasion; EPE)/microscopic bladder neck invasion and seminal vesicle invasion (SVI) currently classified as pT3a and pT3b lesions, respectively, does not uniformly indicate poor oncologic outcomes. Accurate risk stratification of current pT3 disease is therefore required. We herein further determined the prognostic impact of these histopathologic lesions routinely assessed and reported by pathologists, particularly their combinations. We assessed consecutive 2892 patients undergoing radical prostatectomy for current pT2 (n = 1692), pT3a (n = 956), or pT3b (n = 244) disease at our institution between 2009 and 2018. Based on our preliminary findings, point(s) were given (1 point to focal EPE, microscopic bladder neck invasion, or unilateral SVI; 2 points to nonfocal/established EPE or bilateral SVI) and summed up in each case. Our cohort had 0 point (n = 1692, 58.5%; P0), 1 point (n = 243, 8.4%; P1), 2 points (n = 657, 22.7%; P2), 3 points (n = 192, 6.6%; P3), 4 points (n = 76, 2.6%; P4), and 5 points (n = 32, 1.1%; P5). Univariate analysis revealed associations of higher points with significantly worse biochemical progression-free survival, particularly when P4 and P5 were combined. In multivariable analysis (P0 as a reference), P1 (hazard ratio [HR], 1.57; P = .033), P2 (HR, 3.25; P < .001), P3 (HR, 4.01; P < .001), and P4 + P5 (HR, 5.99; P < .001) showed significance for the risk of postoperative progression. Meanwhile, Harrell C-indexes for the current pT staging, newly developed point system, and the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score were 0.727 (95% CI, 0.706-0.748), 0.751 (95% CI, 0.729-0.773), and 0.774 (95% CI, 0.755-0.794), respectively, for predicting progression. We believe our data provide a logical rationale for a novel pathologic T-staging system based on the summed points, pT1a (0 point), pT1b (1 point), pT2 (2 points), pT3a (3 points), and pT3b (4 or 5 points), which more accurately stratifies the prognosis of prostate cancer.

BACKGROUND: Radical surgery for cervical cancer has inherent benefits, and as upfront or post neoadjuvant chemotherapy (NACT), is extendable to locally advanced cancer cervix (LACC), with postoperative radiotherapy (PORT) for high-risk factors. Objective of the study was to compare the effectiveness and survival between non-PORT and PORT in high-risk early stages.
METHODS: Radical hysterectomies conducted between January 2014 and December 2017 were evaluated and followed till December 2019. Clinical, surgical-pathologic characteristics, and oncological outcomes were compared between non-PORT and PORT groups. A similar comparison was made between alive and dead patients within each group. The impact of PORT was assessed.
RESULTS: Of 178 radical surgeries, early-LACC constituted 70%. Most (37%) of the patients belonged to stage 1b2, while stage 2b formed 5%. Mean age of patients was 46.5 years; 69% were below 50 years of age. Abnormal bleeding (41%) was the predominant symptom, followed by postcoital (20%) and postmenopausal bleeding (12%). Upfront surgeries formed 70.2%, and the average waiting period was 1.93 months (range: 1-10 months). PORT patients were 97 (54.5%) in number and the remaining formed the non-PORT group. Mean follow-up was 34 months, with 118 (66%) alive patients. Significant adverse prognostic factors were tumors >4 cm (44.4% patients), positive margins (10%), lymphatic vascular space invasion (LVSI; 42%), malignant nodes (33%), multiple metastatic nodes averaging seven (range: 3-11), and delayed (>6 months) presentation, but not deep stromal invasion (77% patients) and positive parametrium (8.4% patients). PORT overcame the adverse effects of tumors >4 cm, multiple metastatic nodes, positive margins, and LVSI. Total recurrences (25%) were balanced for both groups, but recurrences within 2 years were significantly more for PORT. Two-year overall survival (78%) and recurrence-free survival (72%), median overall survival (21 months), and median recurrence-free interval (19 months) were significantly better for PORT, with the complication rates being similar.
CONCLUSIONS: PORT had significantly better oncological outcomes compared to non-PORT. Multimodal management is worthwhile.

OBJECTIVE: This study was performed to evaluate concordance between clinical and pathologic staging of non-small cell lung cancer (NSCLC) in our hospital network.
METHODS: We retrospectively reviewed records of 417 patients with NSCLC who received curative surgery and whose pathology was evaluated in our hospital between 2016 and 2021. Cytology, tissue pathology, and associated clinical, surgical, and imaging information were retrieved from hospital digital records.
RESULTS: The cohort included 214 female and 203 male patients aged 20.6-85.8 years. Median times among staging computed tomography and surgery (105 days [interquartile range (IQR) 77.0-143.0]), positron emission tomography and surgery (78.5 days [IQR 56.0-109.0]), and endobronchial ultrasound-guided transbronchial needle aspiration and surgery (59 days [IQR 42-94]) indicated that Australian guidelines of <42 days between original referral and commencement of treatment were not being met in the majority of cases. Discordance between clinical TNM (cTNM) and pathologic TNM staging was 25.9%, including 18.4% cases that were clinically understaged and two patients with undetected stage IVA disease. cTNM understaging was significantly associated with time between the final staging investigation and surgery (p = .023), pleural (p < .05) and vessel (p < .05) invasion, and diagnosis of high-grade adenocarcinoma (p = .001).
CONCLUSIONS: Discordance between clinical and pathologic staging of NSCLC is associated with tumor histopathologic characteristics and treatment delays. Although tumor factors that lead to discordant staging cannot be controlled, reduced time to surgery may have resulted in better outcomes for some patients in this potentially curable lung cancer cohort.

Staging and reporting of cancers of the urinary tract have undergone major changes in the past decade to meet the needs for improved patient management. Substantial progress has been made. There, however, remain issues that require further clarity, including the substaging of pT1 tumors, grading and reporting of tumors with grade heterogeneity, and following NAC. Multi-institutional collaborative studies with prospective data will further inform the accurate diagnosis, staging, and reporting of these tumors, and in conjunction with genomic data will ultimately contribute to precision and personalized patient management.

UNASSIGNED: Neoadjuvant chemoradiation has been shown to improve survival in locally advanced esophageal and gastroesophageal junction cancer. The purpose of our study was to examine the effects of posttreatment persistent lymph node (LN) disease on overall survival (OS) and recurrence in patients with esophageal adenocarcinoma after neoadjuvant chemoradiation as well as the effect of LN harvest and the potential benefit of adjuvant chemotherapy.
UNASSIGNED: The records of patients who underwent esophagectomy in our hospital from January 2005 until December 2016 were analyzed. Our study group consisted of 509 patients.
UNASSIGNED: Patient groups were created based on pathologic staging after esophagectomy (ypT N) as 22.0% of patients were ypT0 N0, 46.2% had incomplete response only at the primary tumor level (ypT + N0), and 31.8% had at least 1 metastatic lymph node (ypTx N+). Median OS was 58.3 months. The ypTx N+ group was divided into ypTx N1 and ypTx N2 or N3 subgroups based on the number of metastatic lymph nodes. The OS between the 2 groups was not significantly different (median OS, 37.6 vs 29.8 months; P = .097). The disease-free survival did show a statistically significant difference (median disease-free survival, 27.6 vs 13.7 months; P = .007). The LN harvest was not found to be significantly associated with OS. However, administration of adjuvant chemotherapy was a significant prognosticator for increased OS (hazard ratio, 0.590; P = .043).
UNASSIGNED: Our results demonstrate that residual LN disease after neoadjuvant chemoradiation is associated with increased mortality. Adjuvant chemotherapy, but not number of LNs resected, was correlated with increased OS in this subset of patients.

OBJECTIVE: Preoperative neoadjuvant therapy (NAT) is increasingly used in the treatment of patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Because NAT often induces heterogeneous tumor response and extensive fibrosis both in tumor and adjacent pancreatic tissue, pathologic assessment of posttherapy pancreatectomy specimens is challenging. A limited number of studies examined the optimal grossing and sampling methods, tumor response grading (TRG), and the prognostic value of posttherapy tumor (ypT) and lymph node (ypN) stages of treated PDAC patients. In this review, we will provide an overview of the current status and critical issues in pathologic evaluation of PDAC resected after NAT.
METHODS: In PubMed, Google Scholar and Web of Science, we reviewed existing English literature (published up to December 2021) highlighting the most recent ones using electronic databases and authors\' experience to outline the challenging aspects and new perspectives on pathologic assessment of the treated PDAC.
UNASSIGNED: The recent recommendations from the Pancreatobiliary Pathology Society (PBPS) provide the much-needed guidelines for systematic and standardized pathologic evaluation and reporting of treated PDAC for optimal patient care. For treated PDAC, tumor size measured by gross and radiology is not reliable. Histologic validation of tumor size on consecutive mapping sections is recommended for accurate ypT stage. A tumor size of 1.0 cm seems to be a better cutoff for ypT2 for treated PDACs. The published data suggested that the MD Anderson Cancer Center (MDA) TRG system is easy to use, has a better interobserver agreement and better correlation with patient prognosis compared to the College of American Pathologists (CAP) and Evans grading systems and may be used as an alternative TRG system for the CAP cancer protocol.
CONCLUSIONS: Systemic and standardized grossing and sampling are essential for accurate pathologic evaluation and reporting for optimal care of PDAC patients who received NAT. Future studies on optimal sampling and integration of histopathology with artificial intelligence (AI), molecular and immunohistochemical markers are needed for better and personalized care of treated PDAC patients.

Bladder cancer prognosis and treatment are heavily dependent on accurate staging. Traditional imaging and pathologic evaluation of transurethral resection (TUR) specimens have been associated with high rates of clinical understaging at the time of radical cystectomy (RC).
We describe current components and limitations of bladder cancer staging for muscle-invasive bladder cancer (MIBC), and discuss the rationale for inclusion of novel biomarkers and imaging modalities to improve diagnostic accuracy.
We summarize the data informing MIBC staging accuracy using a nonsystematic review of published literature and provide expert opinion on current and emerging standards in MIBC staging.
Nearly 50% of patients undergoing RC are clinically understaged preoperatively. Components of clinical staging include TUR specimen evaluation, bimanual examination under anesthesia (EUA), and cross-sectional imaging of the chest, abdomen, and pelvis. Complete endoscopic resection of visible disease with sampling of muscularis propria is indicated. While histologic features such as tumor size, focality, variant histologic differentiation, and lymphovascular invasion have prognostic utility, insufficient evidence exists to incorporate them into current staging paradigms. For primary tumor staging, conventional computed tomography (CT) has limited accuracy in differentiating non-MIBC from MIBC. Magnetic resonance imaging (MRI) has exhibited superior pT staging accuracy with the validated Vesical Imaging Reporting and Data System. Positron emission tomography (PET)/CT does not increase clinical nodal staging accuracy beyond CT or MRI, and there exists no consensus role for the use of PET in routine clinical staging.
In the absence of reliable biomarkers to serve as staging adjuncts, we continue to rely heavily on basic clinical staging components-TUR with accurate pathologic evaluation, EUA, and standard cross-sectional imaging modalities. MRI shows promising accuracy and interobserver reliability for primary tumor staging.
Effective clinical staging for muscle-invasive bladder cancer estimates local and systemic disease burden and can dictate eligibility for systemic therapy and/or radical cystectomy. Herein, we review the accuracy and limitations of current and emerging staging modalities.

The detrimental impact of lymphovascular invasion (LVI) in prostate cancer (PCa) on biochemical recurrence has been described; the impact of LVI on overall survival (OS) remains unclear. This investigation sought to evaluate the impact of LVI on OS in patients with PCa.
We examined men with nonmetastatic PCa treated with radical prostatectomy between 2010 and 2015. Only men with documented LVI status were included (n = 232,704). Patients were stratified according to final pathologic T stage (pT2, pT3a, and pT3b).
Of the 232,704 patients who met inclusion criteria, 17,758 (8%) were found to have LVI on final pathology. Overall, 174,838 (75%), 40,281 (17%), and 17,585 (8%) patients had pT2, pT3a, and pT3b disease, respectively. Median follow-up was 42.7 months (27.1-58.7). At 5 years, the OS in LVI versus non-LVI patients was 94% versus 95% in pT2 (P = .0004), 92% versus 95% in pT3a (P < .0001), and 86% versus 92% in pT3b (P < .0001). On multivariable analysis, LVI status was not an independent predictor of OS in pT2 disease (hazard ratio, 1.12; 95% confidence interval [CI], 0.93-1.36; P = .2). In pT3a and pT3b disease, presence of LVI had 1.2-fold (95% CI, 1.03-1.44; P = .02) and 1.4-fold (95% CI, 1.20-1.59; P < .001) higher overall mortality than their counterparts without LVI.
Our report demonstrates the detrimental impact of LVI on OS in locally advanced PCa (pT3a and higher). This information may prove valuable when risk stratifying based on final pathology.

For human papillomavirus-associated oropharynx carcinoma treated with definitive surgery, we aimed to find predictors of adverse histopathology indicating the possible need for adjuvant therapy.
Retrospective review.
National Cancer Database.
We analyzed 2347 eligible patients from 2010 to 2015. We evaluated (1) the ability of clinical nodal staging and extranodal extension designation per the AJCC, seventh edition (American Joint Committee on Cancer), to predict histopathology and (2) the likelihoods for adverse postsurgery histopathology by common clinical stages.
Clinical nodal staging predicted pathologic nodal staging 65% of the time, with 24% (569/2347) being upstaged and 11% (251/2347) being downstaged. In patients with cN+ disease, clinical extranodal extension distinction had the following accuracy for pathologic extranodal extension: positive predictive value, 81% (88/109); negative predictive value, 73.1% (505/691); sensitivity, 32.1% (88/274); and specificity, 96.0% (505/526). Patients with cT1-2, N0-N2c, without clinical extranodal extension had the following proportions of pN2+ without pathologic extranodal extension (indicating consideration for adjuvant radiation): cN0, 11%; cN1, 31%; cN2a, 67% (8% downstaged); cN2b, 66% (6% downstaged); and cN2c, 35% (17% downstaged). From this group, patients had the following proportions of pathologic extranodal extension (indicating consideration for adjuvant chemoradiation): cN0, 6%; cN1, 20%; cN2a, 27%; cN2b, 28%; and cN2c, 48%.
For human papillomavirus-associated oropharynx carcinoma, nodal clinical staging per the American Joint Committee on Cancer, seventh edition, predicts pathologic stage about two-thirds of the time, leading to up- and downstaging. Clinical extranodal extension assessment has low sensitivity and moderate predictive capability. With careful selection, definitive surgery can allow patients to often avoid adjuvant chemotherapy and sometimes avoid adjuvant radiation.