N0 M0 Research Articles

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

Practice patterns in management of differentiated thyroid cancer since the 2014 British Thyroid Association (BTA) guidelines

BackgroundThe updated 2014 BTA guidelines emphasised a more conservative, risk adapted model for the management of low-risk differentiated thyroid cancer (DTC). In comparison to historical approach of total thyroidectomy combined with radioactive iodine, treatment de-escalation is increasingly supported. AimsTo evaluate the impact of the updated BTA guidelines on the management of DTC cases at regional UK centre. MethodsAll DTC patients were retrospectively identified from regional thyroid MDT database between Jan2009–Dec2020. Oncological treatment and clinico-pathological characteristics were analysed. Results623 DTC cases were identified; 312 (247 female: 65 male) between 2009 and 2014 and 311 (225 female: 86 male) between 2015 and 2020. Median age is 48 years (range 16–85). By comparing pre- and post-2015 cohorts, there was a significant drop in total thyroidectomy (87.1% vs 76.8%, p = 0.001) and the use of radioactive iodine (RAI) (73.1% vs 62.1%, p = 0.003) in our post-2015 cohort. When histological adverse features were analysed, extra-thyroidal extension (4.2% vs 17.0%, p=< 0.001), lymphovascular invasion (31.4% vs 50.5%, p=<0.001) and multi-centricity (26.9% vs 43.4%, p = 0.001) were significantly increased in the post 2015 cohort. Nonetheless, total thyroidectomy (TT) remains the treatment choice for low risk T1/2 N0 M0 disease in 65.3% (124/190) in post-2015 cohort for several reasons. Reasons include adverse histological features (50.8%), benign indications (32.5%), contralateral nodules (11.7%), patient preference (2.5%), and diagnostic uncertainty (2.5%). ConclusionOur study confirms a move towards a more conservative approach to patients with low-risk DTC in the UK, which is in keeping with the BTA 2014 guideline and international trends, but total thyroidectomy remains prevalent for low risk T1/2 N0 M0 disease for other reasons.

Diagnostic Performance of 18F-rhPSMA-7.3 PET in Men with Newly Diagnosed High-Risk Prostate Cancer and Negative Conventional Imaging.

The LIGHTHOUSE study (NCT04186819) evaluated high affinity radio hybrid (rh) prostate-specific membrane antigen (PSMA)-targeted PET radiopharmaceutical, 18F-rhPSMA-7.3, in patients across a range of prostate cancer (PCa) risk groups. Here, we report findings from a subgroup with high/very high-risk PCa who had no evidence of nodal or metastatic disease on conventional imaging. Treatment-naïve patients scheduled for radical prostatectomy (RP) plus pelvic lymph node (PLN) dissection underwent PET 50-70 min after IV administration of 296 MBq 18F-rhPSMA-7.3. Local readers interpreted the scans prior to RP (performed ≤60 d post-PET) and ahead of a blinded read by 3 central readers. If the local read indicated M1 disease, verification (biopsy, surgery, or confirmatory follow-up imaging) of PET-positive M1 lesions was attempted before treatment. The present analysis evaluates the 18F-rhPSMA-7.3 sensitivity and specificity for detection of PLN metastases in all high/very high-risk patients with negative conventional imaging at baseline who underwent 18F-rhPSMA-7.3 PET and subsequent surgery. Histopathology was used as the standard of truth (SoT). Additionally, the M1 verified detection rate (VDR; % of patients with true positive (TP) M1 lesions using histopathology or follow-up imaging as SoT out of all patients scanned) was assessed in an extended population of all patients who had 18F-rhPSMA-7.3 PET regardless of surgery. The sensitivity and specificity for PLN detection among 174 men with very/high-risk PCa and negative conventional imaging ranged from 24-33% and 92-96%, respectively, across readers (Table 1a). Across readers, M1 lesions were identified in 28-51 of the 197 patients in the extended population, giving an overall M1 detection rate of 14-26%. Of the identified lesions, 16-25 were successfully verified (predominantly using follow-up imaging as SoT) as TP, providing a M1 VDR of 8.1-13% (Table 1). 18F-rhPSMA-7.3 PET provides clinically useful information on the presence of both N1 and M1 disease prior to surgery in high/very high-risk PCa patients who were staged N0 M0 on conventional imaging. Specifically, up to 13% of such patients had verified TP M1 lesions. 18F-rhPSMA-7.3 may guide treatment, potentially helping such patients avoid ultimately futile surgery.

Dynamic Prediction of Toxicities in Head and Neck Cancer Radiotherapy by 3D Convolutional Neural Network Using Daily Cone-Beam CTs

Radiotherapy (RT) is essential in head and neck cancer (HNC) treatments, but often causes significant toxicity. Different machine learning models have shown promise in predicting RT-induced toxicity, but none have yet integrated the fluctuating anatomical changes. By integrating daily cone-beam CTs (CBCT) allowing sequential anatomical views, our aim is to build a dynamic predictive model for three major HNC RT toxicities: reactive feeding tube placement, hospitalization and radionecrosis (RN). 292 HNC cases treated with curative RT between 2017 and 2019 at our institution were retrospectively analyzed for clinical and radiological data. VoxelMorph, a deep deformable registration model, integrated the daily anatomical deformations between each CBCT and the planning CT, then converted them to Jacobian determinant matrix (Jf). Resnet, a convolutional neural network with multiple layers was trained using a 5-fold cross validation to integrate both radiological and clinical data. Each toxicity was classified as a binary decision using the cross-entropy loss to account for a class imbalance. Its predictive performance was compared to the baseline model using only clinical data. The cohort included 78% men and 22% women, with a median age of 63 years (range 35-84). Primary cancer sites were 46% oropharynx, 19% larynx, 14% oral cavity, 7.5% nasopharynx, 5% hypopharynx, 4% unknown primary and 5% others; and stage ranged between Tx-4b N0 and 3b M0 (AJCC 8th Ed). Induction chemotherapy, concurrent chemotherapy, and adjuvant RT was used in 9%, 57% and 20% of patients, respectively. The incidence of feeding tube, hospitalization and RN was 19.9%, 7.2%, and 3.8%, respectively. Integrating Jf from the 10th RT CBCT showed better accuracy for each toxicity prediction: feeding tube (69.1% > 57.2%), hospitalization (75.3% > 63.1%) and RN (85.8% > 75.7%). Integrating both the raw CBCT and Jf improved hospitalization prediction (79.0% > 73.6%). Substituting Jf for the raw CBCT improved the prediction for RN (79.7% > 74.7%) and hospitalization (73.6% > 64.4%). For feeding tube, predictive performance of the Jf model trained against deformations showed a positive correlation between its performance and the RT received (r2 > 0.9) with increasing RT fractions, with a maximum accuracy of 83.1% at the 25th fraction. No such correlation was found for RN or hospitalization prediction. To our knowledge, this is the first study showing promising results to predict HNC RT toxicities using daily per-treatment CBCT. Next steps involve integrating both the radiomic and the dosimetric inputs to build a more powerful model. This could expand to predict therapeutic outcomes and, ultimately, could guide decisions in individualized RT.

Final Analysis of a Phase III Controlled Randomized Study of Stereotactic Body Proton Therapy or Conventionally Fractionated Proton Therapy for Early Prostate Cancer: PCG GU002

To determine if stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. Multicenter, randomized, controlled, open-label, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score ≤6, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 by AJCC 7th Ed. Eligible participants were randomly assigned (initially 1:1 and later 2:1 ratio) to CFPT (79.2 Gy in 44 fractions for 9 weeks) or SBPT (38 Gy in 5 fractions for 1 week). Concurrent or adjuvant androgen deprivation therapy was not allowed. The primary endpoint was freedom from failure (FFF) at 2 years, defined as the first occurrence of local, regional, or distant recurrence, biochemical failure by the Phoenix definition (increase of PSA ≥2 ng/mL over the nadir PSA), or the start of salvage therapy including ADT. Secondary endpoints included GI and GU grade ≥2 toxicity according to CTCAE v4 criteria, as well as health-related quality of life (HRQoL) metrics assessed by AUASI and EPIC scores. Non-inferiority would be declared if the 1-sided 95% confidence interval limit for the difference in 2-year FFF rate was below 4.2% between both groups by Clopper-Pearson exact method. Between November 2010 and September 2020, 133 patients were enrolled and randomly assigned to CFPT (n = 45) or SBPT (n = 88). Median follow-up was 5 years (IQ 3.9-5.2), with the last patient enrolled followed for at least 2 years. The 2-year FFF was 100% for both groups, fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. By KM estimates, 5-year FFF was 97.4% and 100% (P = 0.1), and the 5-year OS was 97.1% and 95.5% (P = 0.46) for patients treated with CFPT and SBPT, respectively. The cumulative incidence of any grade ≥3 toxicities at 5 years was 0% and 5.7% (P = 0.14) for patients treated with CFPT and SBPT, respectively. The frequency of GI grade ≥2 toxicity at 6 months was of 0% and 2.3% (P = 0.55), and at 2 years was of 6.7% and 3.4% (P = 0.69) for patients treated with CFPT and SBPT, respectively. The frequency of GU grade ≥2 toxicity at 6 months was of 2.2% and 5.7% (P = 0.42), and at 2 years was of 8.9% and 5.7% (P = 0.54) for patients treated with CFPT and SBPT, respectively. Changes in HRQoL scores at 2 years were similar between groups (Table). SBPT is non-inferior to CFPT regarding FFF and associated with similar long-term toxicity rates and HRQoL metric scores.

325. CAMRELIZUMAB IN COMBINATION WITH CHEMOTHERAPY VERSUS CHEMORADIOTHERAPY FOR THE CONVERSION OF UNRESECTABLE ESOPHAGEAL CARCINOMA: A PROSPECTIVE CLINICAL STUDY PROTOCOL

Abstract Background Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC. Methods All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2–3 N0 M0 or T2–3 N+ M0 will be included. They will be treated with radical surgery within 4–8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after half of the planned number of patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission. Discussion We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC. Trial registration: This trial protocol has been registered on NIH Clinical Trials database (www.clinicaltrials.gov/, NCT05176002). The posted information will be updated as needed to reflect protocol amendments and study progress.

663 Squamous Cell Carcinoma of the Scalp Following Synthetic Hair Transplantation: A Case Report

Abstract Androgenetic alopecia is the most common form of hair loss. Surgical treatment options include autologous and synthetic hair transplantation. Synthetic hair fibres can overcome the challenges of poor hair quality and density however there are reports of severe cutaneous complications following their use. We report a case of an advanced squamous cell carcinoma (SCC) of the scalp in an adult male patient following chronic artificial hair transplants. The fungating mass eroded the inner cortex of the left parietal bone without intra-cranial extension on CT. Indeterminate lymph nodes in the parotid gland and level III of the left neck were identified on CT and MRI. Resection of the artificial hair fibres and SCC with a craniectomy, total parotidectomy with facial nerve preservation and upper neck dissection were performed. There was extensive dural involvement not detected on pre-operative imaging, which involved the superior sagittal sinus and was unresectable. The dural disease was fulgurated. The defect was reconstructed with a titanium plate and DIEP flap. Final histopathology showed a moderately differentiated pT4a N0 M0 SCC. The patient received adjuvant proton beam therapy and at 18 months post-operatively is recurrence free. Development of scalp SCC following synthetic hair transplantation has been described, although a clear causation has not been defined. Clinicians should be aware of this presentation and aim to achieve an early diagnosis, timely referral to an appropriate specialist and prompt management.

Modification of fast-track surgery during partial nephrectomy

The present study aimed to assess the efficacy of the multimodal fast-track surgery (FTS) program supplemented with the exclusion of renal thermal ischemia, urinary tract drainage, and postoperative wound management in patients undergoing partial nephrectomy for localized T1 RCC.&#x0D; Methods. A total of 150 patients diagnosed with localized RCC in stage T1 N0 M0 were initially enrolled in this prospective randomized study, with 75 patients assigned to each study group. Patients undergoing perioperative management following the FTS program were randomly assigned to the main study group. The control group comprised patients receiving standard postoperative care. The study specifically involved patients with kidney neoplasms not exceeding 7 cm in the largest diameter based on computed tomography data. Tumor size, localization, and the volume of functioning parenchyma were considered in the assessment.&#x0D; Results. Among the patients included, 24 cases (16%) underwent radical nephrectomy due to technical difficulties arising from tumor spread to the kidney hilum, rendering them ineligible for further analysis. Consequently, the clinical analysis focused on 126 patients. Within the main group, 64 cases (50.8%) of RCC underwent randomization, and the multimodal FTS program was applied during partial nephrectomy. The control group comprised 62 patients (49.2%).&#x0D; The median postoperative bed day in the main group was 1.5 days less compared to the control group, with values of 3.2 [2; 4] days versus 5 [4; 7] days, respectively (p &lt; 0.001). Intraoperative complications occurred in 5 cases (4.0%) involving blood loss exceeding 1 liter (4 cases in the main group and 1 case in the control group). Transfusion of blood components occurred only once when the hemoglobin level dropped below 70 g/l.&#x0D; In the early postoperative period, a total of 9 complications (7.1%) were observed with pyelonephritis lasting more than 3 days diagnosed in 4 cases (3.2%) and wound suppuration in 1 case (0.8%). Despite the absence of drainage in postoperative wounds within the main group, ultrasound examinations revealed small retroperitoneal hematomas (up to 100 ml) requiring drainage in 3% of cases.&#x0D; Conclusions. The multimodal FTS program for patients with localized RCC during partial nephrectomy, coupled with the exclusion of central thermal ischemia of the kidney, avoidance of retroperitoneal space drainage, and early patient activation, demonstrated a significant reduction in postoperative bed while maintaining a comparable level of perioperative complications.

Efficacy of Partial Nephrectomy in the Management of Unpredicted pT3a Renal Cell Carcinoma

Purpose: To compare the oncological outcomes between patients with pathologic T3a (pT3a) renal cell carcinoma (RCC) who underwent partial nephrectomy (PN) and radical nephrectomy (RN).Materials and Methods: We retrospectively reviewed 149 patients with pT3a N0 M0 RCC who underwent PN and RN between 2001 and 2012. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method and prognostic factors were identified using Cox proportional hazard regression models.Results: A total of 41 recurrences (27.5%) and 24 cancer related death (16.1%) were observed during a median follow-up of 136 months (interquartile range, 77–163 months). We observed no significant differences in the RFS and CSS between the PN and RN (RFS: 85.4±64.0 months vs. 75.9±52.8 months, p=0.061; CSS: 153.2±52.5 months vs. 124.9±59.8 months, p=0.292). The surgical method did not affect the tumor recurrence and patients’ survival. On multivariable Cox regression analysis, only tumor size remained associated with worse RFS (hazard ratio [HR], 1.237; 95% confidence interval [CI], 1.132–1.350; p&lt;0.001) and CSS (HR, 1.156; 95% CI, 1.027–1.302; p=0.017).Conclusions: Due to the large tumor size, there may be hesitation in performing PN concerning pT3a in postoperative biopsy. Our study findings suggest that since tumor size is the only prognostic factor, PN can be performed in pT3a as long as there is no thrombus in the renal vein.

Is wedge a dirty word? Demographic and facility-level variables associated with high-quality wedge resection

ObjectivesAlthough sublobar resections have gained traction, wedge resections vary widely in quality. We seek to characterize the demographic and facility-level variables associated with high-quality wedge resections. MethodsThe National Cancer Database was queried from 2010 to 2018. Patients with T1/T2 N0 M0 non–small cell lung cancer 2 cm or less who underwent wedge resection without neoadjuvant therapy were included. A wedge resection with no nodes sampled or with positive margins was categorized as a low-quality wedge. A wedge resection with 4 or more nodes sampled and negative margins was categorized as a high-quality wedge. Facility-specific variables were investigated via quartile analysis based on the overall volume and proportion of high-quality wedge or low-quality wedge resections performed. ResultsA total of 21,742 patients met inclusion criteria, 6390 (29.4%) of whom received a high-quality wedge resection. Factors associated with high-quality wedge resection included treatment at an academic center (3005 [47.0%] vs low-quality wedge 6279 [40.9%]; P < .001). The 30- and 90-day survivals were similar, but patients who received a high-quality wedge resection had improved 5-year survival (4902 [76.7%] vs 10,548 [68.7%]; P < .001). Facilities in the top quartile by volume of high-quality wedge resections performed 69% (4409) of all high-quality wedge resections, and facilities in the top quartile for low-quality wedge resections performed 67.6% (10,378) of all low-quality wedge resections. A total of 113 facilities were in the top quartile by volume for both high-quality wedge and low-quality wedge resections. ConclusionsHigh-quality wedge resections are associated with improved 5-year survival when compared with low-quality wedge resections. By volume, high-quality wedge and low-quality wedge resections cluster to a minority of facilities, many of which overlap. There is discordance between best practice guidelines and current practice patterns that warrants additional study.

Perioperative safety and outcomes following radical prostatectomy in setting of locally advanced, node positive, and metastatic prostate cancer.

e17108 Background: Historically, definitive surgical management with radical prostatectomy (RP) has only been considered an option for the treatment of localized prostate cancer (PCa). However, recent data may suggest a role for RP in advanced PCa treatment. Currently, there is limited data on the safety and perioperative outcomes of RP in this setting. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) new procedure targeted database. Methods: RP procedures performed between 2019-2020 were identified. Patients were stratified to compare the effect of locally advanced disease (T3-4), node-positivity (N+), and metastasis (M+) against patients with localized (T1-2 N0 M0) PCa. Baseline demographics and 30-day outcomes, including operative time, hospital length-of-stay, 30-day mortality, readmissions, reoperations, major complications, minor complications, and surgery-specific complications, were compared between groups. Results: Pathologic staging data was available for 9,276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor-complications in the locally-advanced cohort, but no significant difference in major-complications, 30-day-mortality, readmissions, or rectal injuries. In comparison, while node-positivity was associated with longer operative time, LOS, and incidence of 30-day renal failure, it was not associated with a higher rate of any major, minor or surgery-specific complication. Similarly, RP for metastatic cases appeared to be comparably safe to those with M0 disease, although they were associated with a slightly higher rate of bleeding, prolonged-NG-tube use, and ureteral obstruction. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to localized prostate cancer. Given the previously demonstrated survival benefit in treating the primary tumor in advanced disease with radiation therapy, there may be a role for the RP in treating advanced PCa. Further studies are needed to better characterize the risks and benefits of surgery in these patients.

Role of Adjuvant Chemotherapy in Early-Stage Combined Small Cell Lung Cancer

BackgroundThe role of adjuvant therapy in completely resected primary tumors that have components of both non–small cell lung cancer and small cell lung cancer (combined SCLC) is poorly understood. We sought to determine the potential benefits of adjuvant chemotherapy in patients who undergo complete resection for early-stage combined SCLC. MethodsOverall survival of patients with pathologic T1-2 N0 M0 combined SCLC who underwent complete resection in the National Cancer Database from 2004 to 2017, stratified by adjuvant chemotherapy vs surgery alone, was evaluated by multivariable Cox proportional hazards modeling and propensity score–matched analysis. Patients treated with induction therapy and those who died within 90 days of surgery were excluded from analysis. ResultsOf 630 patients who had pT1-2 N0 M0 combined SCLC during the study period, 297 patients (47%) underwent complete R0 resection. Adjuvant chemotherapy was administered to 63% of patients (n = 188), and 37% of patients underwent surgery alone (n = 109). In unadjusted analysis, the 5-year overall survival was 61.6% (95% CI, 50.8-70.7) for patients who underwent surgery alone and 66.4% (95% CI, 58.4-73.3) for patients who underwent adjuvant chemotherapy. In multivariable and propensity score–matched analysis, there were no significant differences in overall survival between adjuvant chemotherapy and surgery alone (adjusted hazard ratio, 1.16; 95% CI, 0.73-1.84). These findings were consistent when limited to patients who underwent lobectomies or to healthier patients who have at most 1 major comorbidity. ConclusionsIn this national analysis, patients with pT1-2 N0 M0 combined SCLC treated with surgical resection alone have similar outcomes to those who undergo adjuvant chemotherapy.

Timing of rectal cancer surgery after short-course radiotherapy: national database study.

Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database. Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)-) N0 M0 and T1-3(MRF-) N1 M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression. Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139). There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR.

The Utility of Inflammatory Serum Markers in the Assessment of Perioperative Morbidity after Radical Cystectomy for Bladder Cancer.

Background and Objectives: To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods: We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results: The median age at RC was 73 yr (IQR 67-79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2-28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien-Dindo grade 1-2) while 100 (36.9%) experienced major complications (Clavien-Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15-4.90, p = 0.02), (OR 1.51, 95%CI 1.26-1.98, p = 0.09), and (OR 1.35, 95%CI 1.17-2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15-4.16, p = 0.02; OR 2.18, 95%CI 1.13-4.44, p = 0.02, respectively). Conclusions: In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial

AimsAdding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. Materials and methodsParticipants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. ResultsBetween September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. ConclusionGrade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Prognostic factors and a dynamic model on cancer-specific survival for T1a N0 M0 glottic cancer: A population-based analysis and clinical validation.

The survival rate varies tremendously in T1a N0 M0 glottic cancer patients, which may be associated with the difference on patients' characters, such as age, treatment, and marital status. The objective of this study is to identify the vital factors and construct a dynamic prognostic model for predicting the cancer-specific survival (CSS) of patients with T1a N0 M0 glottic cancer. The data of T1a N0 M0 glottic cancer patients were extracted retrospectively from the SEER database between 2004 and 2015, which were randomly divided into the training dataset (70%) and the validation dataset (30%). The training cohort was used to identify independent prognostic factors and build the prognostic nomogram. While the validation cohort was used to validate the applicability of the newly constructed model. The model was evaluated with the discrimination, the calibration, and the clinical benefit. The external data collecting from a medical center were used to validate the performance of the prognostic model. Totally, 3286 eligible patients in the data of the SEER database and 139 eligible patients in our external clinical cohort were finally identified. 5 independent prognostic factors (age, marital status, Grade, primary site surgery, and chemotherapy) were identified and applied to develop the dynamic prognostic tool. C-indexes, receiver operating characteristic curves, calibration curves, and decision curve analyses proved that the prognostic nomogram showed excellent predictive accuracy, ability, and prognostic value. Using internal and external cohorts, the validation of the model also proved its reliability. Prognostic factors for T1a N0 M0 glottic cancer were identified. The novel web-based prognostic prediction tool may be beneficial in clinical decision-making and has value in risk stratification, personalized treatment, and clinical trial design.

Is lobectomy sufficient for multifocal papillary thyroid microcarcinoma?

ImportanceMultifocal papillary thyroid microcarcinoma (PTMC) has been associated with a higher incidence of lymph node involvement, bilateral involvement, and extrathyroidal extension compared to unifocal papillary thyroid cancer (PTC). ObjectiveTo describe the incidence and determinants of survival for patients with multifocal PTMC using the Surveillance, Epidemiology, and End Result (SEER) database. Design, setting, participantsThe SEER registry was utilized to calculate survival trends for patients with PTMC between 2010 and 2015. Patient data was then analyzed with respect to age, sex, race, multifocality, and types of surgery rendered. Main outcomes and measuresOverall Survival (OS) and Disease Specific Survival (DSS). Results22,283 cases of papillary thyroid microcarcinoma (T1a N0 M0) were identified. The cohort was composed of 82.6 % females, and about 82 % of patients were of white race. The mean age at diagnosis was 51.9 years. Multifocal PTMC was present in 32.2 % of the tumors (n = 7186). 73.9 % of patients underwent total thyroidectomy and 23.0 % received lobectomy. OS at 2 and 5 years was 98 % and 95 %, respectively. Multivariate analysis revealed that age, sex, and multifocality were determinants of OS. Only age was a determinant of DSS. Kaplan-Meier survival analysis revealed that multifocal PTMC had similar mean OS between lobectomy and total thyroidectomy patients (69.59 months versus 69.82 months). Conclusions and relevancePTMC has a good prognosis. Our analysis revealed that age was a determinant of OS and DSS; sex and multifocality were also prognosticators for OS. The type of surgery, whether lobectomy or total thyroidectomy, was not a determinant of survival in multifocal PTMC.

MP19-15 EXPLORING PERCEPTIONS OF THE RISK OF RECURRENCE IN RENAL CELL CARCINOMA: EVIDENCE FROM A SURVEY OF PRACTICING PHYSICIANS

You have accessJournal of UrologyCME1 Apr 2023MP19-15 EXPLORING PERCEPTIONS OF THE RISK OF RECURRENCE IN RENAL CELL CARCINOMA: EVIDENCE FROM A SURVEY OF PRACTICING PHYSICIANS Rituparna Bhattacharya, Caroline Vass, Cathy Anne Pinto, Kelley Myers, Kentaro Imai, Cooper Bussberg, Shawna R. Calhoun, and Christine Poulos Rituparna BhattacharyaRituparna Bhattacharya More articles by this author , Caroline VassCaroline Vass More articles by this author , Cathy Anne PintoCathy Anne Pinto More articles by this author , Kelley MyersKelley Myers More articles by this author , Kentaro ImaiKentaro Imai More articles by this author , Cooper BussbergCooper Bussberg More articles by this author , Shawna R. CalhounShawna R. Calhoun More articles by this author , and Christine PoulosChristine Poulos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003244.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The treatment landscape for early-stage renal cell carcinoma (RCC) following nephrectomy is rapidly evolving, especially with the approval of pembrolizumab adjuvant therapy in the United States. Exploratory survey questions aimed to quantify qualitative descriptors of the level of risk of recurrence and to examine physicians’ perceptions of risk and its determinants. METHODS: The survey questions were included in a survey completed by physicians experienced with treating nonmetastatic RCC in the United States. Physicians were asked to (1) assign each of four categories of the risk of post nephrectomy disease recurrence (low, intermediate-low [int-low], intermediate-high [int-high], and high) to selected risk ranges; (2) categorize the risk of recurrence for three patient vignettes; and (3) assign an expected time until disease recurrence for two additional vignettes. Descriptive statistics were used. RESULTS: 250 physicians (64% oncologists, 36% urologists) completed the survey. The median risk levels assigned by oncologists were <20% for low, 21%-50% for int-low, 51%-80% for int-high, and 51-80% for high risk. Urologists’ median risk levels were identical to those of oncologists in the sample, except for the int-high level, which urologists assigned 21%-50%. On average, physicians perceived an individual with pT3, Fuhrman Grade 3, N0, M0 tumor and ECOG Performance status (PS)=1 as int-low risk. Int-high risk was the median perceived risk level assessed for the following two vignettes: pT2, N0, M0, Fuhrman grade 4 tumor with sarcomatoid feature and ECOG PS 0; and pT3, N1, M0, Fuhrman grade 3 tumor and ECOG PS 1. More than one-third of physicians expected a patient with pT3 tumor to remain disease free for 2-3 years post nephrectomy (n=95; 38%) if N0 M0, and 1-2 years (n=92; 36.8%) if N1 M0. CONCLUSIONS: Physicians’ perception of risk of recurrence post nephrectomy is critical when evaluating patient eligibility for and choosing to recommend adjuvant therapy. This exploratory analysis provides insights into risk perceptions among oncologists and urologists. Source of Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e271 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rituparna Bhattacharya More articles by this author Caroline Vass More articles by this author Cathy Anne Pinto More articles by this author Kelley Myers More articles by this author Kentaro Imai More articles by this author Cooper Bussberg More articles by this author Shawna R. Calhoun More articles by this author Christine Poulos More articles by this author Expand All Advertisement PDF downloadLoading ...

Minimum Volume Standards: An Incentive To Perform More Radical Cystectomies?

BackgroundMinimum volume standards (MVS) for hospitals and/or surgeons remain a subject of debate. Opponents of MVS emphasize the possible negative effects of centralization, such as an unwanted incentive to perform surgery. ObjectiveTo evaluate whether the introduction of MVS for radical cystectomy (RC) in the Netherlands resulted in more RCs outside guideline-recommended indications. Design, setting, and participantsAll RCs performed for bladder cancer in the Netherlands between January 1, 2006 and December 31, 2017 were identified in the Netherlands Cancer Registry. During this period, two MVS were sequentially implemented for RC. RCs in intermediate-volume hospitals (hospitals that approximated the MVS) were compared with RCs in high-volume hospitals (hospitals exceeding the MVS by ≥5 RCs/yr) in a period before and a period after implementation of each of the two MVS. Outcomes measurements and statistical analysisDescriptive analyses were performed to evaluate whether hospitals performed more RCs outside the recommended indication (cT2–4a N0 M0) and whether an increase in the number of RCs towards the end of the year could be observed. Results and limitationsAfter MVS implementation, no clear shift towards disease stages outside the recommended indication for RC was observed in comparison to the period before the MVS. Results for high-volume and intermediate-volume hospitals were similar. In addition, no increase in RCs towards the end of the year was evident. ConclusionsWe did not find evidence indicating an unwanted incentive to perform more RCs as a result of MVS in the Netherlands. Our results further strengthen the case for MVS implementation. Patient summaryWe evaluated whether criteria for the minimum number of radical cystectomies (surgical removal of the bladder) that hospitals have to perform caused urologists to perform more of these operations than necessary in order to meet the minimum level. We found no evidence that minimum criteria led to such an unwanted incentive.

DISC1 as a prognostic biomarker correlated with immune infiltrates in gastric cancer

Multiple mental diseases could arise in people who have the disrupted in schizophrenia 1 (DISC1) gene. However, it was unknown how DISC1 might contribute to the development of tumors and immune responses. We extracted data from the Cancer Genome Atlas (TCGA) and TISIDB databases from stomach adenocarcinoma (STAD) patients, which revealed that DISC1 overexpression was closely associated with tumor histological type (mucinous vs. tubular, OR = 2.860, CI = 1.423–5.872, p = 0.004), as well as tumor stage and grade. Furthermore, the higher the DISC1 expression, the lower the overall 10-year survival rate. Patients with low DISC1 expression had a significantly longer progression-free interval (PFI) and disease-specific survival (DSS) than patients with high DISC1 expression. However, patients with higher DISC1 expression in the T3&T4, N0&N1 and M0 subgroups had poorer prognosis in terms of OS, DSS and PFI, as could be seen in the subgroup survival analysis. Public datasets were used to predict lncRNA-miRNA-DISC1 regulation. DISC1 was significantly up-regulated in GC(gastric cancer), and its expression levels showed a moderate to strong positive correlation with infiltration levels of effector memory T cells (Tem) and central memory T cells (Tcm), and a negative correlation was observed with Th17 cells and NK CD56bright cells. In addition, concomitant with the high expression of the DISC1 gene was a decrease in MHC-I (Major Histocompatibility Complex-I)expression and an increase in MHC-II expression, and altered chemokine expression. The upregulation of CXCL12 and CXCR4 expression could be caused by an increase in DISC1 expression.The above expression variability and correlation suggest a role for DISC1 in regulating tumor immunity in GC. These findings suggest that high expression of DISC1 could be an independent prognostic factor for GC.