Stage pT1 Research Articles

Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer

PurposeThe aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC).MethodsData of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001–2015, were analyzed.ResultsILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan–Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08–2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78–0.91), LVSI (hazard ratio 1.75, 95% CI 1.12–2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03–5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02–1.07), LVSI (hazard ratio 3.62, 95% CI 1.92–6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73–0.89).ConclusionThe histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.

The dysfunctional immune response in renal cell carcinoma correlates with changes in the metabolic landscape of ccRCC during disease progression

Renal cell carcinoma is an immunogenic tumour with a prominent dysfunctional immune cell infiltrate, unable to control tumour growth. Although tyrosine kinase inhibitors and immunotherapy have improved the outlook for some patients, many individuals are non-responders or relapse despite treatment. The hostile metabolic environment in RCC affects the ability of T-cells to maintain their own metabolic programme constraining T-cell immunity in RCC. We investigated the phenotype, function and metabolic capability of RCC TILs correlating this with clinicopathological features of the tumour and metabolic environment at the different disease stages. Flow cytometric analysis of freshly isolated TILs showed the emergence of exhausted T-cells in advanced disease based on their PD-1high and CD39 expression and reduced production of inflammatory cytokines upon in vitro stimulation. Exhausted T-cells from advanced stage disease also displayed an overall phenotype of metabolic insufficiency, characterized by mitochondrial alterations and defects in glucose uptake. Nanostring nCounter cancer metabolism assay on RNA obtained from 30 ccRCC cases revealed significant over-expression of metabolic genes even at early stage disease (pT1-2), while at pT3-4 and the locally advanced thrombi stages, there was an overall decrease in differentially expressed metabolic genes. Notably, the gene PPARGC1A was the most significantly down-regulated gene from pT1-2 to pT3-4 RCC which correlated with loss of mitochondrial function in tumour-infiltrating T-cells evident at this tumour stage. Down-regulation of PPARGC1A into stage pT3-4 may be the ‘tipping-point’ in RCC disease progression, modulating immune activity in ccRCC and potentially reducing the efficacy of immunotherapies in RCC and poorer patient outcomes.

HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study.

Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC). This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically nonmetastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. Among the 61 patients with d-MIBC, 14 were HER2 + and 47 HER2 - . Age less than 70 years [hazard ratio (HR): 0.312, CI: 0.16-0.59, P <0.001] and HER2 + status (HR: 0.40, CI: 0.19-0.85, P =0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2 + status was a significant predictive factor for the pT2 stage (HR): 36.8, CI: 4.83-797.41, P <0.01). Age less than 70 years (HR: 0.15, CI: 0.05-0.42, P <0.001) and HER2 + status (HR: 0.11, CI: 0.02-0.54, P =0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. HER2 + status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2 + status not only consistently predicted a favorable T stage after RC, but also predicted better survival than pathological outcomes.

Impact of circumferential resection margin on survival in ampullary cancer: retrospective analysis.

Ampullary carcinoma is a clinically variable entity. This study aimed to evaluate prognostic factors for the outcome of resected ampullary carcinoma patients with particular intent to analyse the influence of surgical radicality. Patients undergoing resection between 2002 and 2017 were analysed. Clinicopathological parameters, perioperative outcome and survival were examined. Risk factor analysis for postresection survival was performed. Resection margin status was evaluated according to the revised classification for pancreatic adenocarcinoma. A total of 234 patients were identified, 97.9 per cent (n = 229) underwent formal resection, while 2.1 per cent (n = 5) underwent ampullary resection. Histological subtypes were 46.6 per cent (n = 109) pancreatobiliary, 34.2 per cent (n = 80) intestinal, 11.5 per cent (n = 27) mixed, and 7.7 per cent (n = 18) undetermined. In the pancreatobiliary group, tumours were more advanced with more vascular resections, pT4 stage, G3 differentiation and pN+ status. Five-year overall survival was significantly different for pancreatobiliary compared to intestinal (51.7 per cent versus 72.8 per cent, P = 0.0087). In univariable analysis, age, pT4 stage, pN+, pancreatobiliary subtype and positive resection margin were significantly associated with worse overall survival. Long-term outcome was significantly better after true R0 resection (circumferential resection margin-, tumour clearance >1 mm) compared with circumferential resection margin+ (<1 mm) and R1 resections (5-year overall survival: 69.6 per cent, median overall survival 191 months versus 42.4 per cent and 53 months; P = 0.0017). Postresection survival of ampullary carcinoma patients is determined by histological subtype and surgical radicality. Intestinal differentiation is associated with less advanced tumour stages and better differentiation, which is reflected in a significantly better overall survival compared to pancreatobiliary differentiation. Despite this, true R0-resection is a prognostic key determinant in both entities, achieving 5-year survival in two-thirds of patients.

Should the Baseline MRI Staging Criteria Differentiate Between Mucinous and Classical Rectal Adenocarcinoma?

To compare baseline MR imaging features for pre-treatment staging between rectal mucinous adenocarcinoma (RMAC) and rectal classical adenocarcinoma (RCAC), and to investigate whether the subtype of mucinous carcinoma influences MRI evaluation criteria and high-risk tumors identifying. A total of 306 patients who underwent surgical rectal cancer resection were retrospectively reviewed in the study. MR imaging parameters of the primary tumor and lymph nodes (LNs) were compared between two subtypes. Logistic regression and receiver operating characteristic analyses were performed to test significant associations between LN imaging parameters and malignant LN status in RMAC and RCAC, respectively. The length of mucinous tumors was larger than RCAC tumors in pT3 and pT4 stage. For pN0 patients, the long and short diameters of the largest LN on MRI were more likely to be larger in RCAC than RMAC. For pN+patients, the proportion of LNs exhibiting internal heterogeneity in RMAC was obviously greater than that in RCAC. The best cut-off value of the largest short diameter of malignant LNs was 6.05mm for RMAC and 8.05mm for RCAC. And the highest AUC for predicting LNs metastases based on the largest short diameter was 0.794 for RMAC using 6mm size cut-off, and 0.667 for RCAC using 8mm cut-off. The imaging features that were associated with LN metastases were different between RMAC and RCAC, and different size criteria of LNs was suggested to distinguish high-risk tumors. Clinicians should stay vigilant of LN status and take histologic subtypes into consideration before assigning clinical strategies.

Primary Melanoma Histopathologic Predictors of Sentinel Lymph Node Positivity: A Proposed Scoring System for Risk Assessment and Patient Selection in a Clinical Setting.

Background and Objectives: The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in identifying the patients eligible for adjuvant therapy. Objectives: The purpose of our study was to investigate the clinical and histologic aspects of primary melanomas that correlate with the likelihood of a positive SLNB result. Materials and Methods: A total of 101 primary melanoma patients who underwent sentinel lymph node biopsies were included in the study. General patient demographics were obtained as well as localization and melanoma-specific characteristics of primary melanoma from histologic reports in addition to data derived from SLNB melanoma histopathology reports. Results: The patients with positive SLN results had a statistically significant increased Breslow thickness (3.8 mm vs. 1.97 mm, p = 0.002), higher mitotic index rate (5/mm2 vs. 2/mm2, p = 0.009), as well as the presence of ulceration (68.4% vs. 31.6%, p = 0.007). Univariate regression analysis showed the Breslow thickness (p = 0.008), the mitotic index rate (p = 0.054), the presence of ulceration (p = 0.009), as well as the pT3-4 stage (p = 0.009) to be significant predictors of SLN positivity. The optimal cut-off values for Breslow thickness and the number of mitoses scores were determined based on ROC curve analysis. Using the Breslow thickness, mitotic index rate, presence of ulceration, and pT3-4 stage significant coefficients from the univariate regression model, a chance prediction score was developed. Conclusions: The newly developed and proposed scoring system can aid in patient selection for SLN biopsy by facilitating a more efficient risk assessment in the detection of lymph node metastases in melanoma patients.

Management of pT1 CRC detected on the colorectal cancer screening programme (Basque Country. Spain)

Abstract Background The Bowel Cancer Screening Programme (BCSP) started in 2009 with faecal immunochemical test (FIT, with cut-off 20µg/g faeces) every 2 years (for 50-69 year- olds). 2.518.715 people were invited until 2021. Participation rate was 70.4% with 5.3% positive rate and 92.7% adherence to colonoscopy. Colorectal cancer (CRC) detection rate was 2.28 ‰ with 70.6% found in initial stage. The PT1 (stage I) represented 40% of the total cancer detected (4,050 in the overall period). Objectives To compare the characteristics and management of pT1 CRC. Methods Retrospective cohort study including pT1 CRC Stage I diagnosed after colonoscopy in positive FIT from 2009-2017. Variables: sex, age groups, endoscopic and surgical treatment, CRC recurrence and survival. Chi-square, Logistic Regression, SPSS v.23. Results Of the 1,523 CRC detected, 585 were detected as pT1 and I stage (38.4%). 73.4% in men and by age group 59% over 60 years-old. 48.5% were treated with surgery and 51.5% with endoscopic resection. No significant differences were found adjusted by sex and age regardless of treatment. In 57.6% of patients under surgery, CRC was not reported by pathological analysis. All cases followed up by colonoscopy with variability in the number of surveillances over time. 4.1% (24) had CRC recurrence with 87% detected in the surveillance, no significant differences regardless of the treatment. 1.5% (9) died due to CRC progression. Conclusions Apart from the high number of CRC detected in early stages by the screening Programme, an important number of cases are reported as pT1 CRC. Endoscopic resection is one of the treatments of choice without significant impact either in recurrence of neoplasia or mortality. However, surgical procedure shows overtreatment because of the high number of cases without CRC after the procedure. Therefore, endoscopic resection could be the main choice to treat pT1 CRC. Key messages • Endoscopic resection is one of the treatment of choice without impact in recurrence for the pT1 CRC detected through the BCSP. • The Basque BCSP obtains excellent participation rate, reflected in early detection and treatment of pre and malignant lesions.

Lymph node staging in grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

ObjectiveThe aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. MethodsMulticenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1–2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. Results298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5–52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06–0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07–0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). ConclusionStaging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

Evaluation of immunohistochemistry pan-cytokeratin and Victoria blue double staining in the assessment of pT3 and pT4a colorectal cancer staging

Evaluation of immunohistochemistry pan-cytokeratin and Victoria blue double staining in the assessment of pT3 and pT4a colorectal cancer staging

Safety and Efficacy of Partial Omentectomy in Laparoscopic Distal Gastrectomy for pT3-T4a Stage Gastric Cancer.

Partial omentectomy (PO) has been gradually applied in laparoscopic gastrectomy for gastric cancer (GC); however, its efficacy remains unclear. The purpose of this study was to assess the safety and efficacy of PO in laparoscopic distal gastrectomy for pT3-T4a stage GC. From June 2019 to May 2021, 108 patients with pT3 or pT4a stage GC who underwent laparoscopic distal gastrectomy were retrospectively included and divided into the PO (n=58) and total omentectomy (TO, n=50) groups. The surgical outcomes, recurrence patterns and postoperative 2-year overall survival (OS) rates were compared between the PO and TO groups. The PO group showed a shorter operation time than the TO group (183.9±21.6 vs 197.6±22.7 min, p=0.002). Less intraoperative blood loss (155.3±113.0 vs 178.8±154.4 mL, p=0.336) and intraoperative complications (5.1% vs 12.0%, p=0.298) were also observed in the PO group than in the TO group, but the difference was not significant. The numbers of retrieved lymph nodes (LNs) and metastatic LNs, postoperative hospital stays and postoperative complications in the two groups were comparable (p>0.05). Moreover, the postoperative overall recurrence rates (25.9% vs 26.0%, p=0.987) and the 2-year OS rates (63.8% vs 65.4%, p=0.437) in the PO and TO groups were also comparable. TO was not an independent prognostic factor for GC patients (HR=0.806, p=0.443). In laparoscopic distal gastrectomy, PO could provide better surgical outcomes and comparable oncological outcomes compared to TO for patients with pT3-T4a stage GC, suggesting that PO may be an acceptable surgical procedure for these patients.

The Role of Tumor Bed Boost in Breast Cancer Patients with HER2-Positive Disease Treated with Breast Conservation Therapy

Retrospective and post-hoc trial analyses have supported the omission of the tumor bed radiation boost in HER2-positive patients undergoing breast-conservation surgery in the era of HER2-directed therapy. In this analysis, we sought to describe the national patterns of care of tumor bed boost and its association with overall survival (OS) in this population. We queried the National Cancer Database to identify all female patients with HER2-positive invasive breast carcinoma treated with lumpectomy. Patients who were treated with neoadjuvant chemotherapy and those with metastatic disease at diagnosis were excluded from analysis. Clinical and demographic information and treatments were analyzed using standard T and χ2 tests. Predictors of receipt of tumor bed boost and predictors of death were identified with multivariable logistic regression. The Kaplan-Meier method was used to evaluated overall survival. We identified 6,620 female patients diagnosed with HER2-positive invasive breast carcinoma between 2006 and 2017. Of these patients, 2,825 (43%) were treated with a boost and 3,795 (57%) were not; 4,698 (71%) were hormone receptor positive and 1,909 (29%) were hormone receptor negative; 6,333 (96%) had negative surgical margins and 287 (4%) had positive surgical margins; 1,270 (19%) were ≤50 years of age and 5,350 (81%) were >50. On multivariable analysis, receipt of tumor bed boost was associated with age ≤50 years (Odds ratio [OR] 1.3, p<0.01), hormone receptor negative (OR 1.3, p<0.01). Factors associated with a higher risk for death included age >50 years (OR 2.4, p<0.01), positive surgical margins (OR 1.7, p<0.01), pN1 (OR 1.3, p = 0.03), pN2 (OR 2.3, p<0.01), pN3 (OR 3.2, p<0.02), and pT2 (OR 2.2, p<0.01) stage. Tumor bed boost was not associated with improved OS when compared to no boost among patients with HER2-positive disease who go on to receive adjuvant systemic therapy (HR 1.06, p = 0.60), even among patients who meet ASTRO tumor bed boost recommendation criteria (HR 0.90, p = 0.60), including age ≤50 with any grade, age 51-70 with high grade, or positive margin. A tumor bed boost is commonly implemented in HER2-positive breast cancer patients undergoing breast-conserving surgery and adjuvant radiation. This data supports previous retrospective and post-hoc trial analyses in omitting the tumor bed boost and treating patients who will receive adjuvant systemic therapy with whole breast radiation alone, provided that the patient receives HER2-directed therapy.

Early Results of the French Multicenter, Randomized SHARE Trial Comparing Whole Breast Irradiation vs. Accelerated Partial Breast Irradiation in Postmenopausal Women with Early-Stage Breast Cancer

The aim is to report toxicity and cosmetic outcomes at 3 and up to 9 years of follow-up of post-menopausal patients randomized to receive either standard whole breast irradiation (WBI), including hypofractionated options, versus accelerated partial breast irradiation (APBI). From December 2010 to July 2015, 1006 patients were enrolled in 34 French centers. Among the whole population, 28 patients who did not meet the final selection criteria or withdrew consent were excluded leading to a modified intention to treat analysis dataset of 978 patients (WBI: n = 488; APBI: n = 490). Median age (65y) and tumor stage pT1 (99%) rates were similar in both arms. Patients had conservative surgery with clip placement in the tumor bed. Clear margins (> 2mm) were observed in 99% of the patients. In both arms, 96-97% of the patients had negative sentinel lymph node biopsy. The median time interval between surgery and radiotherapy was 57d in WBI vs 62d in APBI. WBI schedules consisted of 50 Gy in 25 fr+16 Gy (n = 212) or 40 Gy in 15 fr (n = 156) or 42.5 Gy in 16 fr (n = 120). APBI arm consisted of 38.5 Gy or 40 Gy in 10 fr, 2 fr/day. Overall, 94 patients from the APBI arm finally received standard WBI. For statistical considerations, SHARE trial, sponsored by UNICANCER (NCT01247233) is a non-inferiority randomized controlled trial comparing APBI versus WBI in terms of local control as primary objective. Secondary endpoints were severe toxicity (NCI-CTCAE v4 grade ≥ 2), and cosmetic results. For both outcomes, we estimated the cumulative incidences (CI) using Kalbfleish and Prentice method, considering disease relapse, secondary cancer or death as competing events. Treatment effect (APBI vs WBI) was estimated by cause-specific Hazard Ratios (cs-HR) from Cox models. Median follow-up was 5.8y (range, 0.13-9.5). The number of deaths was 27, and the number of local relapses was 8. Among the 978 patients, 582 and 396 had finally WBI and APBI, respectively. The rates of post-operative hematoma, edema and infection were low: 8-9%, 2%, 3-2%, respectively. When considering any type of severe toxicity, we observed a significant reduction rate in APBI compared to WBI: cs-HR = 0.73 (95% confidence interval: 0.61-0.88); p = 0.001, and 3-year CI of severe toxicity at 45% in WBI vs 36% in APBI arm. The difference was also in favor of APBI when considering breast skin toxicity alone: cs-HR = 0.55 (0.44-0.70), p<0.001 and 3-year CI at 36% in WBI vs 21% in APBI arm. Conversely, for breast other toxicities, WBI was found less toxic than APBI with a 3-year CI of 8% vs 15%, respectively. When considering cosmetic results, we observed no significant difference between the two arms in both evaluations by physicians and patients. Historically SHARE is the first APBI trial that included hypofractionated schedules in the standard arm. We report increased risk of severe toxicity and skin breast toxicity in standard arm as compared with APBI arm without any difference in terms of cosmetic results. Longer follow-up is needed.

Subcutaneous Leiomyosarcoma: An Aggressive Malignancy Portending a Significant Risk of Metastasis and Death.

Subcutaneous leiomyosarcoma (LMS) is a rare, poorly understood variant. The current literature on the subject is sparse, consisting of isolated case reports and small clinicopathologic studies compromised by the inclusion of both its more common and indolent counterpart, cutaneous LMS (atypical intradermal smooth muscle neoplasm), as well as highly aggressive deep-seated tumors. Thus, precise clinicopathologic characterization is limited. Cases of subcutaneous LMS reviewed at the University of Michigan and Cleveland Clinic from 1994 to 2022 were included in this retrospective study. A total of 39 cases were identified. The mean age was 61 years, and the cohort was predominantly male (23/39; 59%). Tumors averaged 4.2cm and most commonly arose on the extremities (32/39; 82%). The majority (38/39; 97%) were diagnosed at an early pathologic stage (pT1 or pT2). Histopathologically, most tumors were well-circumscribed and were assigned a Fédération Nationale des Centers de Lutte Contre le Cancer grade of either 1 or 2 (24/39; 62%). The majority (22/39; 56%) appeared to arise in association with a blood vessel. Of the 36 cases with accessible clinical data and follow-up (mean 34mo, range 0 to 94mo), 12 (33%) were noted to have metastasized, with the lung representing the most common anatomic location. One case recurred locally. Six of 36 patients (17%) died from the disease at an average of 47 months after diagnosis (range 16 to 94mo). Metastasis or death from disease was significantly associated with the Fédération Nationale des Centers de Lutte Contre le Cancer grade ( P =0.0015), the presence of necrosis ( P =0.032), tumor size ( P =0.049), and AJCC tumor stage ( P =0.036). These data demonstrate that subcutaneous LMS are more aggressive than dermal-based tumors and have a prognosis akin to that of deep-seated LMS.

Recurrent Gleason Score 6 Prostate Cancer After Radiotherapy or Ablation: Should We Observe Them All? Results from a Large Multicenter Salvage Radical Prostatectomy Consortium

BackgroundSalvage radical prostatectomy (sRP) yields poor functional outcomes and relatively high complication rates. Gleason score (GS) 6 prostate cancer (PCa) has genetic and clinical features showing little, if not absent, metastatic potential. However, the behavior of GS 6 PCa recurring after previous PCa treatment including radiotherapy and/or ablation has not been investigated. ObjectiveTo evaluate the oncological outcomes of sRP for radio- and/or ablation-recurrent GS 6 PCa. Design, setting, and participantsRetrospective data of sRP for recurrent PCa after local nonsurgical treatment were collected from 14 tertiary referral centers from 2000 to 2021. InterventionProstate biopsy before sRP and sRP. Outcome measurements and statistical analysisA survival analysis was performed for pre-sRP biopsy and sRP-proven GS 6. Concordance between PCa at pre-sRP biopsy and sRP histology was assessed. Results and limitationsWe included GS 6 recurrent PCa at pre-sRP biopsy (n = 142) and at sRP (n = 50), as two cohorts. The majority had primary radiotherapy and/or brachytherapy (83.8% of GS 6 patients at pre-sRP biopsy; 78% of GS 6 patients at sRP) and whole-gland treatments (91% biopsy; 85.1% sRP). Biopsy GS 6 10-yr metastasis, cancer-specific survival (CSS), and overall survival (OS) were 79% (95% confidence interval [CI] 61–89%), 98% (95–99%), and 89% (78–95%), respectively. Upgrading at sRP was 69%, 35.5% had a pT3 stage, and 13.4% had positive nodes. The sRP GS 6 10-yr metastasis-free survival, CSS, and OS were 100%, 100%, and 90% (95% CI 58–98%) respectively; pT3 and pN1 disease were found in 12% and 0%, respectively. Overall complications, high-grade complications, and severe incontinence were experienced by >50%, >10%, and >15% of men, respectively (in both the biopsy and the sRP cohorts). Limitations include the retrospective nature of the study and absence of a centralized pathological review. ConclusionsGS 6 sRP–proven PCa recurring after nonsurgical primary treatment has almost no metastatic potential, while patients experience relevant morbidity of the procedure. However, a significant proportion of GS 6 cases at pre-sRP biopsy are upgraded at sRP. In the idea not to overtreat, efforts should be made to improve the diagnostic accuracy of pre-sRP biopsy. Patient summaryWe investigated the oncological results of salvage radical prostatectomy for recurrent prostate cancer of Gleason score (GS) 6 category. We found a very low malignant potential of GS 6 confirmed at salvage radical prostatectomy despite surgical complications being relatively high. Nonetheless, biopsy GS 6 was frequently upgraded and had less optimal oncological control. Overtreatment for recurrent GS 6 after nonsurgical first-line treatment should be avoided, and efforts should be made to increase the diagnostic accuracy of biopsies for recurrent disease.

Critical Appraisal of Histologic Grading for Mucoepidermoid Carcinoma of Salivary Gland: Is an Objective Prognostic 2-tiered Grading System Possible?

Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative border, lymphovascular invasion, perineural invasion, atypical mitosis, mitotic index (MI) ≥4/2mm 2 (4/10HPFs), necrosis, and pT4 stage were associated with increased risk of nodal metastasis. The 5-year recurrence-free survival (RFS) was 95%. Significant prognostic factors for RFS included infiltrative border, tumor-associated lymphoid stroma, architectural patterns (macrocystic, microcystic, and noncystic), anaplasia, atypical mitosis, MI, necrosis, lymphovascular invasion, margin, pT stage, and tumor size. Nuclear anaplasia, high mitotic rate, and ≥25% microcystic component were significant independent prognostic factors on multivariate survival analysis. There was no significant difference between low-grade (LG) and intermediate-grade (IG) MECs in terms of risk of nodal metastasis and outcomes using all 4 known grading systems. Rather, high-grade MEC was consistently associated with an increased risk of nodal metastasis at presentation and decreased RFS and distant metastasis-free survival (DMFS) compared with the LG/IG MECs. We therefore recommend simplifying MEC grading to a 2-tiered grading scheme using MI and/or tumor necrosis. Using a 2-tiered grading, high-grade histology independently predict RFS, and is associated with a 25% risk of nodal metastasis, a 5-year RFS of 76%, and a 5-year DMFS of 76%, whereas LG MEC has a nodal metastasis rate of 7.0%, 5-year RFS of 97% and 5-year DMFS of 99%.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial

PURPOSEIn the randomized, single-center, PKUFH phase III trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the two cohorts at 4 years. In the current analysis, we provide 7-year outcomes. MATERIALS AND METHODSPatients with stage pT3-4, positive surgical margins, or prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image-guided intensity-modulated radiotherapy. The primary end point was bPFS. Secondary end points were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS), as estimated using the Kaplan–Meier method. RESULTSBetween September 2011 and November 2016, 144 patients were enrolled, with 73 and 71 in the 72 and 66 Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72 and 66 Gy cohorts (70.3% vs 61.2%; hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.41-1.29; P = 0.274). However, in patients with a higher Gleason score (GS 8-10), the 72 Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66 Gy cohort (66.5% vs 30.2%; HR = 0.37, 95%CI: 0.17-0.82; P = 0.012). In addition, in patients with multiple positive surgical margins (mSM+), the 72 Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR = 0.36, 95%CI: 0.13-0.99; P = 0.037). The 7-year DMFS (88.4% vs 84.9%; HR = 0.93, 95%CI: 0.39-2.23; P = 0.867), CSS (94.1% vs 95.5%; HR = 1.19, 95%CI: 0.42-3.39; P = 0.745), and OS (92.8% vs 94.1%; HR = 1.29, 95%CI: 0.51-3.24; P = 0.594) had no statistically difference between the 72 and 66 Gy cohorts. CONCLUSIONThe current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared to the 66 Gy regimen. However, patients with a higher GS (8-10) or mSM+ might benefit from the 72 Gy regimen, but this requires further prospective research.

PD-L1 protein expression by Combined Positive Score (CPS) in patients with muscle invasive or advanced urothelial carcinoma: a single institution experience

IntroductionImmune checkpoint inhibitors have revolutionized the treatment of patients with advanced urothelial carcinoma (UC) in the frontline and relapsed settings. Lebanon has one of the highest incidence of UC worldwide, yet no data exists regarding the expression of PD-L1 by Combined Positive Score (CPS) in advanced disease.MethodsWe reviewed all patients treated at our institution for high grade UC, stage pT2 and above, between January 2017 and March 2021. We assessed the expression of PD-L1 by immunohistochemistry using 22C3 clone, and analyzed the association between PD-L1 expression and clinicopathological characteristics. PD-L1 positivity was defined as CPS score ≥ 10.ResultsA total of 101 patients with advanced UC were included, with a median age of 71 years (range, 38 to 96 years); 78% were ever-smokers. Ninety-three of 101 patients (92%) had conventional UC and 43 patients (43%) had positive PD-L1 expression, with 12 patients having CPS of 100. The analysis by molecular subtype showed that patients with maximal CPS of 100 were enriched in “basal” molecular subtype. However, no association was found between PD-L1 expression (positive versus negative) and clinicopathological characteristics.ConclusionThe positivity of PD-L1 expression as assessed by CPS using the 22C3 clone in our population was almost comparable to the results reported in the occidental literature. Therefore, PD-L1 expression, as a potential predictor of response to immunotherapy, concerns the same percentage of the Lebanese UC patients.

Mismatch repair deficiency as prognostic factor for stage III small bowel adenocarcinoma: A multicentric international study.

Small bowel adenocarcinoma (SBA) is a rare cancer with an aggressive behavior. No study has specifically addressed the putative prognostic role of mismatch repair status in stage III SBAs. We aimed to investigate whether mismatch repair deficiency is associated with cancer-specific survival in a Western cohort of patients with stage III SBAs. In this retrospective multicentric international cohort study, we enrolled 70 patients who underwent surgically resection for stage III SBAs and we analyzed the frequency of mismatch repair deficiency, tested by immunohistochemistry for mismatch repair proteins and by polymerase chain reaction for microsatellite instability, and its association with cancer-specific survival and other clinic-pathologic factors. We found sixteen (23%) patients with mismatch repair deficient adenocarcinoma, without discordance between immunohistochemical and polymerase chain reaction for microsatellite instability analyses. Mismatch repair deficiency proved to be associated with a better outcome both at univariable analysis (hazard ratio: 0.28, 95% confidence interval: 0.08-0.91, p: 0.035) and in bivariable models adjusted for patient age or gender, tumor site, pT4 stage, tumor budding, and perineural invasion. This study highlights the importance of testing mismatch repair status to improve prognostic stratification in stage III SBAs.

Pre-operative incisional biopsy of oral squamous cell carcinoma: high podoplanin expression is related to perineural invasion and may be a useful predictor of disease progression

Immunohistochemical analysis of podoplanin expression as a pre-operative molecular marker for perineural invasion (PNI) may represent an attractive strategy for surgical management of oral squamous cell cancer (OSCC). We evaluated the relationship between podoplanin expression and PNI in pre-operative incisional biopsies of OSCC. After performing pathological staging and histologic and immunohistochemical evaluation of 83 surgical specimens, we performed multivariable logistic regression analysis to examine the relationship between PNI and independent variables. To evaluate the utility of podoplanin immunopositivity for discrimination of PNI status pre-operatively, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value. We performed receiver operating characteristic curve analysis to evaluate the diagnostic accuracy of podoplanin immunopositivity for predicting PNI alone and in combination with age, T stage, N stage, and index site. We observed podoplanin expression in 42 (50.6%) of all the 83 pre-operative incisional biopsies and 29 of the pre-operative biopsies of the 31 (93.5%) postoperative specimens with PNI. The rate of podoplanin expression was significantly higher in patients with pT3 to pT4 stage and pN+ stage disease. Podoplanin positivity in the pre-operative biopsy showed high sensitivity in predicting PNI in the surgical specimen. Podoplanin expression appears to be an independent pre-operative variable significantly related to PNI and a possibly valuable prognostic marker for therapeutical planning and surgical treatment of OSCC.

Urinary Continence Recovery after Retzius-Sparing Robot Assisted Radical Prostatectomy and Adjuvant Radiation Therapy.

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) allows the preservation of the structures advocated to play a crucial role in the continence mechanism. This study aims to evaluate the association between adjuvant radiation therapy (aRT) and urinary continence (UC) recovery after RS-RARP. For the purpose of the current study, all patients submitted to RS-RARP for prostate cancer (PCa) at a single high-volume European institution between January 2010 and December 2021 were identified. Only patients that harbored pT2 stage with positive surgical margins or pT3/pN1 stage with or without positive surgical margins were included in the analyses. Two groups of patients were identified as follows: patients who had undergone aRT and patients submitted to observation (no-aRT patients). As per definition, aRT was delivered within 1-6 months after surgery. After 1:1 propensity score matching, 124 aRT patients were compared with 124 no-aRT patients who continued standard follow-up protocol after surgery. UC recovery was 81 vs. 84% in aRT vs. no-aRT patients (p = 0.7). In multivariable Cox regression analyses, aRT did not reach the independent predictor status for UC recovery at 12 months. In the subgroup analysis including only aRT patients, only the nerve-sparing technique was independently associated with UC recovery at 12 months. Conversely, the type of aRT (IMRT/VMAT vs. 3D-CRT) did not reach the independent predictor status for UC recovery at 12 months. The current study is the first to address the association between aRT and UC recovery in patients treated with RS-RARP for PCa. Based on our data, aRT is not associated with worse UC recovery. In the cohort of patients treated with aRT, the nerve-sparing technique independently predicted UC recovery.