Pelvic Node Involvement Research Articles

Biochemically recurrent prostate cancer: rationalisation of the approach to imaging

To assess the utility of magnetic resonance imaging (MRI) in addition to the additive benefit of the conventional imaging techniques, computed tomography (CT) and nuclear medicine (NM) bone scintigraphy, for investigation of biochemical recurrence (BCR) post-prostatectomy where access to prostate specific membrane antigen (PSMA) positron-emission tomography (PET)-CT is challenging. Relevant imaging over a 5-year period was reviewed. Ethical approval was granted by the internal review board. All patients with suspected BCR, defined as a PSA ≥0.2 ng/ml on two separate occasions, underwent a retrospective imaging review. This was performed on PACS archive search database in a single centre using search terms "PSA" and "prostatectomy" in the three imaging methods; MRI, CT, and NM bone scintigraphy. All PSMA PET CT performed were recorded. One hundred and eighty-five patients were identified. Patients with an MRI pelvis that demonstrated distant metastases (i.e., pelvic bone metastases or lymph node involvement more cranial to the bifurcation of the common iliac arteries) were more likely to have a positive CT and/or NM bone scintigraphy. The Pearson correlation coefficient between the findings of M1 disease at MRI pelvis and the presence of distant metastases at CT thorax, abdomen, pelvis and NM bone scintigraphy was calculated at 0.81 (p<0.01) and 0.91 (p<0.01) respectively. An imaging strategy based on risk stratification and technique-specific selection criteria leads to more appropriate use of resources, and in turn, increases the yield of conventional imaging methods. MRI prostate findings can be used to predict the additive value of CT/NM bone scintigraphy allowing a more streamlined approach to their use.

DASL-HiCaP: A randomized, phase 3, double-blind trial of darolutamide with androgen-deprivation therapy and definitive or salvage radiation for localized very high-risk prostate cancer.

TPS396 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA), is a standard of care for patients with very high-risk localized prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of patients with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile, and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT used either as primary definitive therapy, or as salvage therapy, for very high-risk PC. Methods: This study is a randomized (1:1), phase 3, placebo-controlled, double-blind, international trial for patients planned for RT who have very high-risk localized PC on conventional imaging; or very high-risk features with PSA persistence or rise within one year following RP. The trial is stratified by previous RP; planned use of adjuvant docetaxel; clinical or pathological pelvic nodal involvement. 1100 participants will be randomized to receive darolutamide 600 mg or placebo twice daily for 96 weeks in combination with SOC (LHRHA for 96 weeks, plus RT starting week 8-24 from randomization). Participants are allowed nonsteroidal antiandrogen in addition to LHRHA for up to 90 days prior to randomization. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival, with secondary endpoints of overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety, and resistance to study treatment. Clinical trial information: NCT04136353 .

Somatic BAP1 Loss in Ovarian Serous Borderline Tumor and Recurrent Low-grade Serous Carcinoma From a Germline BAP1 Mutation Carrier.

To the Editor: In a recent issue, Dr. Oliva and colleagues proposed the use of the immunohistochemical markers, Claudin-4 and BAP1, to distinguish between low-grade serous neoplasms and peritoneal mesothelioma 1. This article is of particular interest to us, as we have recently published on a cohort of 119 clinically annotated low-grade serous carcinomas, confirmed by central pathology review, with molecular profiling by targeted next-generation sequencing 2. In this cohort, we encountered 1 patient who represents an unusual exception to relying on loss of BAP1 expression to exclude the diagnosis of a low-grade serous neoplasm. This was a 59-yr-old female who underwent comprehensive surgical staging for bilateral ovarian masses. Final pathology revealed a stage IIIC serous borderline tumor involving bilateral ovaries (Fig. 1A), associated with noninvasive peritoneal implants and involvement of pelvic lymph nodes. After 7 yrs, she developed recurrent disease involving the sigmoid colon, in the form of metastatic low-grade serous carcinoma (Fig. 1B). Both primary and recurrent tumors showed a similar immunophenotype, characterized by strong diffuse expression of epithelial/Mullerian markers, including Claudin-4 (Fig. 1C), BerEP4, PAX8, ER, and PR, while negative for markers of mesothelial differentiation, namely, calretinin, and D2-40. Somatic mutational profiling by targeted next-generation sequencing revealed the low-grade serous carcinoma to harbor a BAP1 frameshift mutation (Y241Lfs*2). Germline testing further revealed a heterozygous BAP1 germline mutation (c.1110dupC, p.Met371Hisfs*27). Loss of BAP1 expression by immunohistochemistry in the low-grade serous carcinoma, as well as the prior serous borderline tumor (Fig. 1D), was consistent with bi-allelic inactivation of BAP1 as an early event in the molecular pathogenesis of this case.FIG. 1: Low-grade serous neoplasms associated with germline BAP1 mutation. (A) Ovarian serous borderline tumor showing characteristic hierarchical branching papillae lined by stratified columnar epithelium (inset: ciliated cells observed at high-magnification, consistent with tubal differentiation). (B) Recurrent invasive low-grade serous carcinoma involving muscularis propria of the sigmoid colon, showing infiltrating nests and micropapillae composed of tumor cells with small monotonous nuclei, and scattered psammoma bodies. Immunohistochemical analysis of the serous borderline tumor showing (C) diffuse expression of Claudin-4 and (D) loss of BAP1 expression in tumor cells with retained nuclear staining in non-neoplastic stromal cells.To our knowledge, this represents the first reported case of a BAP1-deficient low-grade serous neoplasm. It illustrates how genetic alterations of oncogenes and tumor suppressor genes are not tissue or disease-specific and emphasizes the importance of applying several cell lineage markers, along with morphologic correlation, for appropriate diagnostic classification of tumor type.

Pathologic primary tumor factors associated with risk of pelvic and paraaortic lymph node involvement in patients with endometrial adenocarcinoma

The presence of lymph node (LN) positivity in endometrial adenocarcinoma (EAC) patients guides adjuvant treatment, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Primary pathologic tumor characteristics may predict risk of LN involvement in EAC patients with limited LN evaluation. Patients diagnosed between 2004–2016 with pathologic T1–T2 EAC in the National Cancer Database who had at least one lymph node sampled at the time of surgery were included. Pathologic primary tumor predictors of LN involvement were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN involvement, nomograms were generated. Among 57,810 EAC patients included, 4002 were node positive. On multivariable analysis, increasing pathologic tumor category (pT2 versus pT1a, odds ratio (OR) 5.43, 95% confidence interval (CI) 4.89–6.02, p &lt; 0.001), increasing pathologic tumor grade (grade 3 versus grade 1, OR 1.62, 95% CI 1.47–1.79, p &lt; 0.001), increase in tumor size per centimeter (OR 1.05, 95% CI 1.04–1.06, p &lt; 0.001), and presence of lymphovascular invasion (LVI) (OR 6.33, 95% CI 5.87–6.83, p &lt; 0.001) were predictive of overall LN positivity. The presence of LVI was a stronger predictor of paraaortic LN involvement (OR 6.43, 95% CI 5.55–7.47, p &lt; 0.001) than pelvic LN involvement (OR 5.42, 95% CI 4.98–5.90, p &lt; 0.001) in multivariable analysis. For patients with limited LN evaluation, pathologic tumor features can be used to estimate the risk of pelvic or paraaortic LN involvement. This information may inform adjuvant treatment decisions and guide future studies.

Characteristic of penile cancer and prognostic factors of inguinal and pelvic lymph node involvement.

Penile cancer is a rare malignancy which inguinal and pelvic lymph node involvement plays a major role in patients' survival. The prognosis of patients with lymph node metastasis is poorer. The objective of the study was to evaluate the prognostic factors for inguinal lymph node and pelvic lymph node involvement. This was a retrospective analytic study of medical records between January 2010 and December 2020. Thirty-nine patients were diagnosed with penile cancer, median age of 59 ± 14.898 (range: 32-86 years) were included in the analysis. Twenty-eight patients underwent inguinal lymph node dissection, 13 patients had inguinal lymph node metastasis (46.4%), 8 patients underwent pelvic lymph node dissection, and 5 patients had pelvic lymph node metastasis (62.5%). Inguinal lymph node metastasis was associated with tumor grading (odds ratio [OR]: 2.92, confidence interval [CI]: 0.123-0.704), lymphovascular invasion (LVI) (OR: 5.182, CI: 0.430-0.996), perineural invasion (PNI) (OR: 3.687, CI: 0.277-0.975), and fixation of inguinal node (OR: 2.463, CI: 0.078-1.195). Pelvic lymph node metastasis was associated with tumor grading (OR: 2.619, CI: 0.033-0.967). Grading, LVI and PNI of primary tumor, and fixation of inguinal node are significantly associated with inguinal lymph node metastasis. While primary tumor grading is significantly associated with pelvic lymph node metastasis. These factors are associated with poorer prognosis.

Assessment of Monitor Units and Gamma Pass Rate for 6 MV and Flattening Filter Free (FFF) Beams in Volumetric Modulated Arc Therapy (VMAT)

Background: In linear accelerators, the treatment field’s uniform intensity is achieved by including a flattening filter in the beam. However, to produce more conformal dose distributions, contemporary radiotherapy practice now frequently uses fluence and aperture modifying techniques, such as volumetric modulated arc therapy. In these circumstances, the flattening filter in the beam manufacturing process is no longer required. It is therefore necessary to compare the monitor units of 6 MV and flattening filter free plans and how it influences the gamma pass rates to determine which is best for treating cervical cancer with pelvic lymph node metastasis. Methods: VMAT plans for fifteen patients with cervical cancer with pathological pelvic lymph node metastasis were included in this study. Each patient had two VMAT plans using conventional 6 MV beam with flattening filter and one with flattening filter free beam (FFF). The VMAT plans were made using two arcs, and then recalculated to give the planned dose distribution to the detectors in a Delta4 phantom. The VMAT plans were irradiated on the Delta4 phantom using an Elekta linear accelerator (6 MV). Results: The mean monitor unit for the 6 MV plans was 506.3 MU and a standard deviation of 48.6 while that of the FFF plans had a mean MU of 701.5 with a standard deviation of 87.6. The total monitor units (MUs) for the FFF plans were significantly greater than the 6 MV plans (p = 6.1 × 10-5). Conclusion: Flattening filter free (FFF) plans require more numbers of monitor units in comparison to conventional 6 MV filtered beams for external radiation of cervical cancer with pelvic lymph nodes involvement.

A machine-learning-based combination of criteria to detect bladder cancer lymph node metastasis on [18F]FDG PET/CT: a pathology-controlled study.

Initial pelvic lymph node (LN) staging is pivotal for treatment planification in patients with muscle-invasive bladder cancer (MIBC), but [18F]FDG PET/CT provides insufficient and variable diagnostic performance. We aimed to develop and validate a machine-learning-based combination of criteria on [18F]FDG PET/CT to accurately identify pelvic LN involvement in bladder cancer patients. Consecutive patients with localized MIBC who performed preoperative [18F]FDG PET/CT between 2010 and 2017 were retrospectively assigned to training (n = 129) and validation (n = 44) sets. The reference standard was the pathological status after extended pelvic LN dissection. In the training set, a random forest algorithm identified the combination of criteria that best predicted LN status. The diagnostic performances (AUC) and interrater agreement of this combination of criteria were compared to a consensus of experts. The overall prevalence of pelvic LN involvement was 24% (n = 41/173). In the training set, the top 3 features were derived from pelvic LNs (SUVmax of the most intense LN, and product of diameters of the largest LN) and primary bladder tumor (product of diameters). In the validation set, diagnostic performance did not differ significantly between the combination of criteria (AUC = 0.59 95%CI [0.43-0.73]) and the consensus of experts (AUC = 0.64 95%CI [0.48-0.78], p = 0.54). The interrater agreement was equally good with Κ = 0.66 for both. The developed machine-learning-based combination of criteria performs as well as a consensus of experts to detect pelvic LN involvement on [18F]FDG PET/CT in patients with MIBC. • The developed machine-learning-based combination of criteria performs as well as experts to detect pelvic LN involvement on [18F]FDG PET/CT in patients with muscle-invasive bladder cancer. • The top 3 features to predict LN involvement were the SUVmax of the most intense LN, the product of diameters of the largest LN, and the product of diameters of the primary bladder tumor.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

ObjectiveTo determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. MethodsRetrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. ResultsOne hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2–3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. ConclusionsInformation from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

PSOR11 Presentation Time: 12:20 PM: Long-Term Experience with Pd-103 Prostate Brachytherapy

<h3>Purpose</h3> Although long-term control rates after low dose-rate brachytherapy are available, the majority of such series report patients treated with I-125 or Cs-131, whereas relatively fewer series have reported long-term results with Pd-103. We herein report our long-term experience using Pd-103. <h3>Materials and Methods</h3> Patients were treated with Pd-103 brachytherapy, either monotherapy or as boost with external beam. bRFS was defined as interval from implant date to biochemical failure using Phoenix criteria, while MFS was defined as the interval from implant to development of radiographic evidence of extraprostatic disease or death from any cause. Cox proportional hazards models were constructed with NCCN risk stratification. We also performed a preliminary dosimetric analysis of prostate D90 and V100 (Day 1) to assess implant quality as a predictive factor for bRFS and MFS. <h3>Results</h3> 495 patients treated between 2004-2019 consisted of 53 very-low, 218 low, 177 intermediate (119 favorable, 58 unfavorable), 32 high, and 15 very high-risk patients; the majority of patients with high-risk disease were treated in the period following ASCENDE-RT. One hundred twenty (24.2%) patients received external beam radiation (EBRT); 197 (39.8%) patients received androgen deprivation therapy. Median follow-up was 4.75 years, (0.1- 16.6 years); 168 (34%) of patients had ≥7 years of follow-up. Overall, biochemical relapse occurred in 32 (6.4%) of patients. At 5, 7, and 10 years post-implant, biochemical control rates (95% confidence) were 93.9% [91.5-96.3%], 93% [90.3-95.7%], and 90% [85.9-94.3%], respectively. Similarly, at 5, 7, and 10- years post-implant, 96.4% [94.3-98.5%], 94% [91.1-96.9%], and 88.7% [84.1-93.6%] of patients were free of metastatic disease or death. Among 9 patients with clinical relapse, 5 patients (1.0%) had pelvic nodal involvement and 4 (0.8%) had distant metastatic disease. With regard to metastases and death, high-risk prostate cancer was significantly associated with worse MFS, HR = 5.69 [1.58-20.5] (multivariate) and bRFS, HR = 3.43 [1.10-10.7]. Median MFS in the high-risk group was 13.7 years post-implant; median bRFS was 8.45 years. Low- and intermediate-risk patients had >80% freedom from metastases and all-cause death at 10 years, p = 0.03. Both low- and intermediate-risk patients had similarly excellent survival after brachytherapy, p = 0.3 (bRFS) and p = 0.11 (MFS). Overall, prostate D90 or V100 were not significantly associated with bRFS or MFS, p > 0.3. However, overall implant quality was high, with a median D90 of 112.7% [102.9-124.4]. <h3>Conclusions</h3> Brachytherapy with Pd¹⁰³ results in excellent long-term biochemical and local control at 5, 7, and 10 years. Dosimetry indicators were not significant predictors in this cohort, presumably because implant quality was consistently high.

561P When to treat the pelvis in node-positive vulvar cancer: Results from the AGO-VOP.2 QS vulva study

The population at risk for pelvic disease in vulvar cancer is poorly described. This results in an overtreatment of a considerable proportion of patients with groin-positive disease. In this retrospective, multicenter analysis, 306 patients with primary node-positive vulvar squamous cell carcinoma (VSCC) after surgical groin staging treated at 33 gynecologic oncology centers in Germany between 2017- 2019 were analyzed with regard to pelvic treatment, risk for pelvic nodal involvement and prognosis. The majority had locally restricted tumors (T1b/T2; 292/306; 95.4%) with a median tumor diameter of 32 mm (2-110mm). Nodal status of the groin(s) was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3 (TNM staging system version 6). Only 35.6% (109/306) received a pelvic LAE – 39.4% unilaterally and 60.6% bilaterally; pelvic nodal involvement was observed in 18.5%. None of the patients with one intranodal metastasis or 2 metastases <5mm and pelvic LAE showed pelvic nodal involvement. Taking only patients with more inguinal disease into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the patients who received pelvic LAE and had positive pelvic nodes received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). In case of histologically detected groin metastases, the risk for pelvic metastasis is low. These data no longer justify uncritical treatment of the pelvis - neither with surgery nor radiotherapy- in groin node-positive vulvar cancer.

An implementation of the learning curve cumulative summation test to evaluate a practicum for endometrial cancer ultrasound staging.

The learning curve cumulative summation (LC-CUSUM) test is commonly used as a quantitative assessment of the individual learning process. This study aimed to evaluate the skill acquisition process for performing ultrasound staging of endometrial cancer using the LC-CUSUM test. Sixty-seven ultrasound examinations performed by two operators were evaluated using the LC-CUSUM test according to their rate of success or failure to correctly stage myometrial invasion, serosa involvement, and pelvic and para-aortic lymph node involvement. The reference standard was the pathologic result. After the learning phase, the cumulative summation (CUSUM) test was applied to assess performance maintenance. The processes achieved satisfactory performance in the majority of the cases according to the established definitions. Operator 1 reached adequate performance within the 30th procedure for all the locations considered, while operator 2 performed fewer than 30 ultrasound examinations by the audit time. The CUSUM test confirmed that the target quality was preserved after the learning phase. Moreover, the ultrasound staging for endometrial cancer was highly accurate. Using the LC-CUSUM test made it possible to monitor the achievement and maintenance of a satisfactory performance quantitatively. The LC-CUSUM test could be a valuable instrument to survey diagnostic pathways in gynecological ultrasonography quantitatively.

Role of MRI in pre-operative staging of endometrial cancer: A diagnostic accuracy study

Endometrial cancer (EC) is a commonly occurring cancer among post-menopausal women. Pre-treatment imaging of the extent of disease can influence the decisions in the management of EC. MRI with its diffusion weighted (DW) images can help in better depiction of the primary tumour, its local extension and extrauterine spread to the peritoneum and lymph nodes. This study was conducted to know the role of MRI for pre-operative staging of endometrial cancer and as a guide for pelvic lymph nodal dissection.It was a descriptive cross-sectional study conducted at a tertiary care hospital patients diagnosed with primary endometrial adenocarcinoma on biopsy. Patients with advanced disease requiring chemotherapy prior to surgery were excluded. Fifty consecutive patients were subjected to MRI Pelvis with abdominal screening in the week preceding definitive surgery, Findings from imaging were compared with final histopathology for concurrence on tumour size, depth of myometrial invasion, presence of adnexal, nodal and cervical stromal involvement.Majority of the patients in this study were post-menopausal women. Sensitivity of MRI for staging of Endometrial Carcinoma in this study was 91.84% and Accuracy was 90%. When compared to HPE for lymph node positivity, MRI had sensitivity of 100%, specificity of 97.87%, PPV of 75%, NPV of 100% and accuracy of 98%.Pre-operative MRI in the week prior to the planned surgery can help in accurately staging the endometrial carcinoma in terms of myometrial infiltration, cervical stromal infiltration as well as pelvic lymph nodal involvement.

Impact of severe obesity in the management of patients with high-risk endometrial cancer: A FRANCOGYN study

ObjectiveTo assess the surgical management and survival of severely obese patients with high-risk endometrial cancer. Materials and methodsData from 269 patients with high-risk endometrial cancer who were treated between 2001 and 2018 were collected from a multicenter database (11 centers). We classified the patients according to their BMI and compared outcomes in two groups: a normal weight group of women with a BMI < 25 kg/m2, and a severe obesity group of women with a BMI ≥ 35 kg/m2. The groups were compared for epidemiologic, pathologic, management, relapse-free survival (RFS) and overall survival (OS) elements. ResultsPatients in the severe obesity group were younger (64 years vs. 68 years, p < 0.05) and had more comorbidities (hypertension, diabetes). They also had more locally advanced tumors and pelvic lymph node involvement (47% vs 24%, p < 0.05). The severely obese patients were less likely to undergo recommended surgical staging, with fewer lumbar aortic dissections than women of normal weight (23% vs 36%, p < 0.05) and fewer pelvic sentinel lymph node biopsies (26.5% vs 12.1%, p < 0.05). No difference in RFS or OS were observed between the two groups. ConclusionPatients with severe obesity and high-risk endometrial cancer have more locally advanced tumors, and are less likely to be managed according to surgical recommendations. However, RFS and OS do not seem to be affected.

Camrelizumab combined with TIP (paclitaxel+cisplatin+ifosfamide) as neoadjuvant treatment of locally advanced penile cancer before lymphadenectomy: An exploratory, phase Ⅱ study.

TPS5093 Background: Penile squamous cell carcinoma (PSCC) is a highly aggressive disease that accounts for 95% of penile cancers and is characterized by a high risk of early locoregional spread and morbidity with subsequent potential for distant dissemination. The lymph node invasion is one of the most important factor that affects the prognosis of PSCC. Penile cancer patients with uninvolved inguinal lymph nodes had a 5-year survival rate of 66% compared with 27% for those with involvement, and penile cancer with the pelvic lymph node involvement have a worse 5-year survival rate that is typically less than 10%. Therefore, this study aims to reduce small lesions to reach the radical lymphadenectomy by camrelizumab combined with TIP in the neoadjuvant treatment of PSCC. Methods: In this single-arm, prospective, phase Ⅱ study, 34 patients with histological or cytological diagnosis of locally advanced PSCC (TX, N2-N3, M0), ECOG performance score of 0-1, planned to be recruited. Enrolled patients with inguinal and/or pelvic lymph node metastasis (positive percutaneous lymph node biopsy) after primary tumor resection of penile cancer were treated with combined therapy including camrelizumab (200 mg, iv, Q3W), paclitaxel (175 mg/m2, iv, Q3W), cisplatin (25 mg/m2, iv, Q3W) and ifosfamide (1200 mg/m2, iv, Q3W) for a total of 4 cycles. The primary endpoint is the rate of pathologic complete response (pCR). Secondary endpoints are event-free survival, overall survival, objective response rate, disease control rate and safety. On the basis of a threshold pCR rate of 13.6%, targeting an expected pCR of 34% and assuming 12 months follow-up, 80% power and a one-sided α = 0.05, this design requires 34 evaluable patients to be accrued over 3 years. Clinical trial information: ChiECRCT20210503.

DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801)—A randomized phase 3, double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation.

TPS5103 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analog (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile, and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or salvage therapy for very high-risk PC. Methods: This study is a randomized (1:1), phase 3, placebo-controlled, double-blind trial for men planned for RT who have very high-risk localized PC on conventional imaging; or very high-risk features with PSA persistence or rise within one year following RP. The trial is stratified by: RP; use of adjuvant docetaxel; pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomization. Participants are allowed nonsteroidal antiandrogen in addition to LHRHA for up to 90 days prior to randomization. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety, and resistance to study treatment. Clinical trial information: NCT04136353.

Patient (pt) population and radiation therapy (RT) type in the long-term phase 3 double-blind, placebo (PBO)-controlled ATLAS study of apalutamide (APA) added to androgen deprivation therapy (ADT) in high-risk localized or locally advanced prostate cancer (HRLPC).

5084 Background: Current management of HRLPC includes long-term ADT with primary RT. Despite definitive primary treatment, these pts have a high risk of metastasis and death. The phase 3 ATLAS study (NCT02531516) is investigating whether treatment intensification with the addition of APA to neoadjuvant and adjuvant treatment with gonadotropin-releasing hormone agonist (GnRHa) and external beam radiation therapy (EBRT) will improve metastasis-free survival (MFS) in high-risk pts. Here we describe (1) the distribution of baseline characteristics in this high-risk pt population and (2) the application of different RT regimens reflecting recent international guidelines and clinical practice changes for pts with HRLPC. Methods: Eligible HRLPC pts (Gleason score [GS] ≥ 8 or 7 and prostate-specific antigen [PSA] ≥ 20 ng/mL and stage ≥ cT2c), with ECOG PS 0/1 and Charlson Comorbidity Index (CCI) ≤ 3 are stratified by GS, pelvic nodal status, use of brachytherapy boost, and region; pts are randomized 1:1 to APA or PBO plus GnRHa for 30 (28-d) treatment cycles. Study treatment is applied neoadjuvant/concurrent to RT with APA 240 mg/d vs bicalutamide 50 mg/d for 4 cycles; another 26 cycles are completed adjuvantly after RT with APA 240 mg/d vs PBO. Primary end point is MFS (time from randomization to first distant metastasis on CT/MRI/bone scan by independent central review blinded to treatment or death from any cause). Imaging is conducted at baseline and q6m from biochemical failure until MFS. The protocol has been amended to include PET imaging (PSMA, fluciclovine, or choline). Results: Pts (N = 1503) were randomized at 266 sites in 24 countries in North America, Latin America, Europe, and Asia. The study is fully enrolled, but ongoing. Baseline characteristics for the total population: median age, 67 yrs; ECOG PS 0/1; 89%/11%; tumor classification at study entry: high-risk, 66%/very high–risk, 34%; median PSA, 6.3 ng/mL; cT2, 44%/cT3, 50%; cN1, 13%. In 90% of ATLAS pts, RT used was standard EBRT to prostate/pelvis over 6-8 weeks (cumulative 78-81 Gy); in 10%, recent hypofractionation schedules (per CHHiP or NRG/RTOG 0415) were applied (20x3 Gy/d or 28x2.5 Gy/d). 5.6% of pts had EBRT combined with brachytherapy (per ASCENDE-RT). Conclusions: Baseline characteristics of the ATLAS study population are reflective of pts with high- and very high–risk features and pelvic nodal involvement undergoing primary RT in clinical practice. The RT schedules applied reflect recent evidence and guideline changes for the use of hypofractionation in this pt population. ATLAS is an example of how RT can be included in phase 3 trials of HRLPC, in combination with next-generation androgen receptor inhibitors (eg, APA). Clinical trial information: NCT02531516.

CONCURRENT CHEMORADIATION WITH WEEKLY CISPLATIN AND PACLITAXEL IN LOCALLY ADVANCED CARCINOMA CERVIX

Introduction:Carcinoma cervix is the most common gynaecological malignancy in women. Concurrent chemoradiotherapy is an effective treatment for locoregionally advanced squamous cell carcinoma of the cervix, with established benefits in both organ preservation and survival. Aims:1. To assess the immediate locoregional response rates of locally advanced squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy using weekly low dose cisplatin and low dose paclitaxel followed by HDR intracavitary brachytherapy. 2. To assess the acute toxicity. Materials and methods:This is a single arm prospective study in which 30 patients with cervical carcinoma of stages IB2-IIIB, presenting to our hospital, were given concurrent chemoradiation: EBRT 50Gy/25# with weekly Cisplatin 30mg/m2 and Paclitaxel 30mg/m2 followed by intracavitary brachytherapy 8Gy/2# and response was assessed, both clinical and radiological, at the end of 6 weeks after completion of therapy, using RECIST criteria. Toxicity was assessed using RTOG morbidity scoring. Results:Clinically, there was complete locoregional response in 27 patients (90%), partial response in 3 patients (10%). Acute toxicities were observed but they were manageable. Diarrhea presented as grade I, II and III in 5 (16.7%), 3 (10%) and 2 (6.7%) patients respectively. Grade Ihaematological toxicity was seen in 7 patients (23.3%) and grade II in 3 patients (10%) during the 5th week of chemo-radiation. Grade I and II skin reactions were seen in 7 patients (23.3%) with grade III reactions in one patient. Grade I bladder toxicity is seen is 2 patients (6.7%). Conclusion:This study shows including a taxane as a radiosensitiser, in the standard concurrent chemoradiation with weekly cisplatin schedule, yields better loco-regional response with acceptable toxicity, especially in locally advanced stages and those with pelvic nodal involvement.

ATOMICC trial: a randomized, open-label, phase II trial of anti-PD1, dostarlimab, as maintenance therapy for patients with high-risk locally advanced cervical cancer after chemoradiation

BackgroundCurrently, women diagnosed with high-risk locally advanced cervical cancer are at high risk of recurrence after treatment with concurrent chemoradiation and represent a population with high unmet need.Primary ObjectiveThe primary...

The best postoperative adjuvant therapy for patients with early stage cervical adenosquamous carcinoma

BackgroundCervical adenosquamous carcinoma (ASC) was previously thought to be a subtype of cervical adenocarcinoma, but recent studies have found that the clinical features of the two diseases are different. Moreover, the pathological characteristics, survival, prognosis, and optimal ASC therapy remain unknown. This study aims to retrospectively analyze the postoperative survival of patients with early-stage ASC and to evaluate their condition after treatment with postoperative concurrent chemoradiotherapy (CCRT) and prophylactic irradiation of the para-aortic lymphatic drainage area.MethodsThis study enrolled 131 patients with pathologically confirmed ASC screened from 3502 patients with confirmed stage I–II cervical cancer diagnosis who had completed surgical treatments in our hospital. Among the 131 enrolled patients, 75 patients received CCRT, 33 patients received chemotherapy (CT), and 23 patients did not receive adjuvant treatment (named surgery alone (S alone). Of the 75 patients CCRT, 43 patients received prophylactic irradiation of the para-aortic lymphatic drainage area. The efficacy of the postoperative treatments of patients among groups (CCRT, CT, and S alone) was compared.ResultsThe median follow-up time, age, and overall survival (OS) were 76 months, 43 years, and 74 months, respectively. The 3- and 5-year survival rates were 82% and 71.4%, respectively. The median disease-free survival (DFS) was 64 months. Cox regression analysis showed that postoperative adjuvant treatment modalities and positive lymph node metastases were associated with OS and DFS. Patients who received CCRT treatment had higher OS and DFS than those with CT and S alone. Prophylactic irradiation of the para-aortic lymphatic drainage area did not improve the OS and DFS of patients with CCRT treatment. However, further subgroup analysis suggested that it might improve survival rates in patients who had positive pelvic lymph nodes as confirmed by postoperative pathology.ConclusionPostoperative CCRT improved the survival rates in patients with early-stage ASC. The value of prophylactic irradiation of the para-aortic lymphatic drainage area remains debatable, but it may benefit patients with pelvic lymph node involvement.

Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.

The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.