Unifocal Tumors Research Articles

Volumetric and functional outcomes at 1-year between percutaneous-ablation and partial-nephrectomy for T1b renal tumors.

Indication for percutaneous-ablation (PA) is gradually expanding to renal tumors T1b (4-7cm). Few data exist on the alteration of renal functional volume (RFV) post-PA. Yet, it is a surrogate marker of post partial-nephrectomy (PN) glomerular filtration rate (GFR) impairment. The objective was to compare RFV and GFR at 1-year post-PN or PA, in this T1b population. Patients with unifocal renal tumor≥4cm treated between 2014 and 2019 were included. Tumor, homolateral (RFVh), contralateral RFV, and total volumes were assessed by manual segmentation (3D Slicer) before and at 1 year of treatment, as was GFR. The loss of RFV, contralateral hypertrophy, and preservation of GFR were compared between both groups (PN vs. PA). 144 patients were included (87PN, 57PA). Preoperatively, PA group was older (74 vs. 59years; P<0.0001), had more impaired GFR (73 vs. 85mL/min; P=0.0026) and smaller tumor volume(31.1 vs. 55.9cm3; P=0.0007) compared to PN group. At 1year, the PN group had significantly more homolateral RFV loss (-19 vs. -14%; P=0.002), and contralateral compensatory hypertrophy (+4% vs. +1,8%; P=0.02, respectively). Total-RFV loss was similar between both (-21.7 vs. -19cm3; P=0.07). GFR preservation was better in the PN group (95.9 vs. 90.7%; P=0.03). In multivariate analysis, age and tumor size were associated with loss of RFVh. For renal tumors T1b, PN is associated with superior compensatory hypertrophy compared with PA, compensating for the higher RFVh loss, resulting in similar ΔRFV-total between both groups. The superior post-PN GFR preservation suggests that the preserved quantitative RFV factor is insufficient. Therefore, the underlying quality of the parenchyma would play a major role in postoperative GFR.

Kidney sparing surgery in upper tract urothelial carcinoma: paradigm change in surgical treatment for ureter cancer.

To extend the indications of kidney-sparing surgery (KSS) for ureter cancer by comparing the oncological outcomes between patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) or KSS. We retrospectively reviewed 708 patients with UTUC who underwent RNU (N = 646) or KSS (N = 62) between 2011 and 2019 to analyze the oncologic outcomes and prognostic factors. Subgroup analyses were performed for patients with unifocal ureteral urothelial carcinoma (UC). No significant difference was observed in the overall survival (OS) or cancer-specific survival (CSS) between RNU and KSS (distal ureterectomy with reimplantation (N = 33), ureterectomy with ileal ureter (N = 14), ureteroscopic tumor resection (N = 10), and ureterectomy with ureteroureterostomy (N = 5)). Among 269 (38.0%) patients with unifocal ureteral UC, 219 and 50 patients underwent RNU and KSS, respectively. OS and CSS were not significantly different between these two groups. Pathologic stage was a significant risk factor in multivariate analysis (hazard ratio = 2.621; p = 0.000). Among 646 RNU patients, 219 (33.9%) had unifocal ureteral UC, 40 (18.3%) with low-grade tumors. Among these, 13 (5.9%) patients with unifocal, low-grade and small (< 2cm) tumors received nephroureterectomy. Kidney-sparing surgery should be regarded as an important alternative to RNU for patients with unifocal ureteral UC thought to have noninvasive disease to preserve renal function and reduce overtreatment.

Real-time Fluorescent ICG and 99m-Tc Nanocolloid Tracer Navigation in Bilateral Sentinel Lymph Node Mapping of Vulvar Cancer

The effectiveness of sentinel lymph node (SLN) biopsy has been validated by two prospective trials, GROINS VI and GOG 1731-2. According to ESGO guideline in patients with unifocal tumors with a diameter of <4 cm, in the absence of suspected inguinal lymph nodes, SLN biopsy is recommended. The use of a radioactive tracer is mandatory.2 Using Indocyanine green (ICG) increase the detection of the vulvar sentinel node from 89.7 to 100%3. Aim of this video is to share our experience about the feasibility, safety and usefulness of the surgical identification of SLN in vulvar cancer using real-time fluorescent indocyanine green with 99m-technetium nanocolloid. Stepwise demonstration of the technique with narrated video footage. Tertiary level hospital "IRCCS Istituto Nazionale dei Tumori", Milano, Italy. A 50-year-old woman was diagnosed with vulvar cancer on biopsy of 1.5 cm size vulvar lesion under the clitoris area and referred to our Operative Unit. F-18 fluorodeoxyglucose positron-emission tomography-computed tomography (PET) showed no extra-vulvar disease. The patient was scheduled for radical vulvectomy and bilateral inguinal sentinel lymph-node biopsy (SLN). In this video the surgical procedure involved double location of SLN, first with the 99m-technetium detector followed by ICG identification. We used an ICG dilution of 2.5 mg/mL in sterile water and injected 4 mL around the tumor 5-10 min before visualization. First a handheld gamma probe used to identify the location of the SLN(s) with 99m-technetium. The fluorescence imaging was performed by the quest imaging system (FLUOPTICS©, Middenmeer, The Netherlands) that combine autofluorescence and fluorescence perfusion imaging. Second, we carried out the SLN biopsy using a dark mood procedure to identify the IGC tracer. The fluorescence imaging enables the detection of these markers through some millimeters of tissue and ICG has the advantage that is visible through the skin4. This video shows a successful combined 99m-technetium and ICG fluorescence image-guided bilateral SLN biopsy in a vulvar cancer patient using a near-infrared (NIR) optical imaging system (FLUOPTICS©). ICG for SLN mapping appears to be safe in women with vulvar cancer with a satisfactory detection rate. This may help in retaining surgical radicality while minimizing operative complications.

Prognostic Factors in Epithelioid Hemangioendothelioma: Analysis of a Nationwide Molecularly/Immunohistochemically Confirmed Cohort of 57 Cases.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study, we aimed to investigate prognostic factors based on clinicopathologic findings in a molecularly/immunohistochemically confirmed nationwide multicenter cohort of 57 EHE cases. Patients had unifocal disease (n = 29), multifocal disease (n = 5), lymph node metastasis (n = 8) and/or distant metastasis (n = 15) at the time of diagnosis. The overall survival rate was 71.4% at 1 year and 50.7% at 5 years. Survival did not correlate with sex, age or histopathological parameters. No survival differences were observed between multifocal and metastatic disease, suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al., dividing the cases into low- (n = 4), intermediate- (n = 15) and high- (n = 3) risk groups. No clinical or histopathological parameters were associated with progressive unifocal disease course. Lymph node metastases at the time of diagnosis occurred in 14.0% of the cases and were mainly associated with tumor localization in the head and neck area, proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previously described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.

Pushing the Limits of Breast-Conserving Surgery with Extreme Oncoplasty

Introduction: We aimed to report the long-term surgical outcomes of extreme oncoplasty techniques in selected patients with unifocal (UF)/cT3 or multifocal-multicentric tumors (MFMC). Material and Methods: Patients who were initially recommended to have mastectomy underwent extreme oncoplastic breast-conserving surgery (eOBCS) including therapeutic reduction mammoplasty, racquet, and round-block mammoplasty, Grisotti flap, or combined technique were included. Preoperative tumor parameters, clinical outcomes, rate of local recurrence, survival, and patients’ satisfaction were assessed. Results: Eighty-six patients with a median age of 51 years were followed for a median follow-up of 75 (8–154) months; 31 (36%) had cT3 and 55 (64%) had MFMC tumors. The majority of patients (83.6%) had invasive cancer. The median UF tumor size was 58 mm (range 51–100) on imaging and 51 mm (range 50–60) on final pathology. The median tumor span for MFMC was 65 mm (range 53–95) on imaging, whereas the median of the largest tumor size was 30 mm (range 22–60) on final pathology. Seventy-one patients (82.5%) were ER-positive, 17 (19.7%) were HER2 positive, and 8 (9.3%) were triple-negative breast cancer. Four patients (4.7%) required further intervention for having positive margins (3 re-excisions, 1 completion mastectomy). Three local recurrences (3.4%) and 10 (11.6%) distant metastasis occurred. The cosmetic outcome was excellent in 37 (43%) patients. No major complications were observed. Conclusions: eOBCS can be a good option for patients who initially require mastectomy. Appropriate patient selection, a multidisciplinary approach, and patient consent are essential steps of the procedure.

The evaluation of locoregional tumoral involvement in the cooccurrence of hashimoto thyroiditis with papillary thyroid cancer: a case controlled study

BackgroundPapillary thyroid carcinoma PTC is the most prevalent of all thyroid carcinomas. On the other hand, Hashimoto’s thyroiditis (HT), as part of the spectrum of autoimmune thyroid diseases, is a major cause of thyroid hypofunction worldwide. Several studies have aimed to indicate a possible correlation between PTC and HT over the years. This study aims to investigate the correlation between HT disease and PTC tumor invasion rate.MethodIn the present cross-sectional study, PTC patients with HT were selected among patients referred to the surgical ward of Shariati hospital from 2016 to 2019 and compared in terms of tumor invasion and central LN dissection. Also, a similar group of PTC patients without HT undergoing total thyroidectomy was selected for comparison. The tumor invasion rate was assessed based on invasion indices obtained from postoperative permanent pathology specimens. These indices included tumor type and size, number of involved LNs, lymphovascular involvement, perineural involvement, thyroid capsule involvement, multifocal or unifocal tumor, extrathyroidal proliferation, marginal status, and necrosis. Data were obtained and compared in the two groups with SPSS version 22.0 software.ResultsBased on the postoperative pathology reports, 50 (56.2%) PTC patients with Hashimoto thyroiditis were compared against 39 PTC patients without Hashimoto thyroiditis. No significant difference was found between the two groups regarding tumor invasion factors such as multifocality, lymphovascular invasion, marginal invasion, extrathyroidal invasion, capsular invasion, and necrosis.ConclusionHT could not be mentioned as an aggravating factor of PTC invasion based on the invasion factors evaluated in pathology specimens.

Abstract OT3-20-03: Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796

Abstract Introduction The aim of the study was to prove efficacy and safety of de-escalation of traditional breast surgery in BC patients who develop cCR after neoadjuvant systemic therapy. Refusal of surgery was offered to exceptional responders after vacuum-assisted tumor bed biopsy and sentinel lymph node biopsy confirmed absence of residual disease (pCR). Materials and methods A single-center prospective study was run in the NMRC n.a. N.N. Petrov. Starting from August of 2020, 35 patients with early сT1-2N0-1M0 (stage Ia-IIb) triple-negative and HER2-positive (both ER+ and ER-) unifocal tumours without DCIS in core-biopsy specimen enrolled in the study. Primary lesions were marked with a single clip in the centre. In cases with nodal involvement (cN1) the affected lymph nodes were also clipped. Patients with triple-negative breast cancer received 4 cycles of AC q21d followed by 12 cycles of weekly paclitaxel and carboplatin AUC 2.0. HER2-positive patients received 4 cycles of AC followed by 4 cycles of docetaxel combined with trastuzumab and pertuzumab q21d. Breast US, mammography and SPECT were used at baseline and at response evaluation. Vacuum-assisted biopsy was performed with 7G needle and US-guidance in the OR simultaneously with the SLNB. VAB protocol included retrieval of the tumor clip as first stage. Subsequently surrounding tissues were sampled, and markers were placed to guide radiotherapy. In case residual tumor was found patients received standard breast-conserving surgery. In case the sentinel lymph nodes were found to be positive, standard level II axillary clearance was performed. HER2-positive patients with pCR confirmed by VAB and SLNB received adjuvant trastuzumab up to one year. HER2-positive patients with residual breast or nodal involvement received trastuzumab emtansine up to one year. In case ER+, all patients received appropriate endocrine-therapy. In case of residual in-breast or nodal involvement patients with triple-negative breast cancer received standart capecitabine. Results The interim analysis included 25 patients in both groups. The median follow-up of disease-free survival for patients is 12 months. In the triple-negative group 12 patients achieved cCR. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 11 patients (91.7%). 1 patient had invasive residual tumor with less than 5% cellularity. FNR in this group was 8.3% (1/12). Patient with invasive residual tumor received standard breast-conserving surgery. All the patients in the TNBC group were also found to be (sn)ypN0. In the HER2-positive group cCR was achieved 13 patients. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 10 patients (77%). 3 patients had invasive residual tumor with less than 5% cellularity. FNR in this group was 23% (3/13). Patients with invasive residual tumor received standard breast-conserving surgery. All HER2-positive patients were found to be (sn)ypN0. One patient with HER2-positive subtype experienced a local reccurence in the postoperative zone 16 months after surgery. Initially, this patient achieved cCR and undergone VAB with SLNB. On final pathomorphologic examination isolated focuses of DCIS were found (ypTisN0). Standard breast-conserving surgery was performed and histologically only DCIS was found. This patient recieved 1-year of Trastuzumab and standard radiotherapy with boost. After the histologic confirmation of local reccurence patient underwent nipple-sparring mastectomy with reconstruction and nowadays she is recieveing therapy with trastuzumab emtansine (T-DM1). Conclusion All visualization modalities fail to provide reliable information on the true rate of pCR. Contemporary systemic therapy regimens after accurate selection of patients, following the inclusion criteria, allows to achieve pCR in 75-90%, thereby reducing the risk of FNR after VAB. The trial continues to enroll patients and further follow-up is needed. Citation Format: Petr Krivorotko, Sergey Yerechshenko, Alexander Emelyanov, Ekaterina Busko, Tengiz Tabagua, Viktoria Mortada, Konstantin Zernov, Alexander Komyakhov, Kirill Nikolaev, Elena Zhiltsova, Larisa Gigolaeva, Roman Pesotsky, Diana Enaldieva, Yana Bondarchuk, Nikolay Amirov, Valentin Channov, Sergey Novikov, Zhanna Bryantseva, Anna Artemyeva, Viktoriya Smirnova, Tatiana Semiglazova, Alexey Belyaev, Vladimir Semiglazov. Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-03.

A comparison of ICG-NIR with blue dye and technetium for the detection of sentinel lymph nodes in vulvar cancer.

The sentinel lymph node (SLN) procedure for vulva cancer is a safe alternative to a radical inguino-femoral lymphadenectomy (IFLN) for small unifocal tumours. SLN evaluation through biopsy and ultra-staging has helped gynaecological oncology surgeons improve operative morbidity with no cost to oncologic safety. Established techniques for groin SLN detection and excision in vulvar cancer use 99mTc-nanocolloid radiotracer and blue dye (BD) for identification of the SLN. Indocyanine green (ICG)-near infrared (ICG-NIR) techniques for SLN mapping have proven utility in other gynaecological cancer sites and is gaining interest as a technique for SLN mapping in vulvar cancer METHODS: Fifty consecutive patients with unifocal vulvar squamous cell cancers of <40mm lateral diameter and with depth of invasion > 1mm underwent SLN mapping and excision using a combination of 99mTc-nanocolloid, BD and ICG. SLN detection results were recorded on a per-patient and per-groin basis. The success rates SLN for detection by individual tracer substance or combinations of tracer were determined by presence of one or more tracer, detectable in the SLN specimen. 92% of patients had a successful SLN procedure. The per-groin detection rate was 84%. All successfully mapped SLN were identified with the combination of ICG-NIR and 99mTc-nanocolloid compared to 69% with BD 99mTc-nanocolloid. Success rates for the SLN procedure were not dependent on prior excision of the primary lesion or operator experience. Incorporation of ICG-NIR into standard SLN mapping protocols may allow for the abandonment of routine use of BD and its poor side effect profile.

The effects of clinicopathological and imaging findings on recurrence and survival in mammary Paget's disease.

Mammary Paget's disease (MPD) is a rare presentation type of breast cancer. The aim of this study was to evaluate the clinicopathological and imaging features affecting the invasive component, loco-regional recurrence, prognosis, and survival of MPD. Patients who had undergone surgery due to MPD in a 10-year period were included. Parameters including mammography and magnetic resonance imaging (MRI) findings, tumor stage, molecular subtype, axillary involvement, presence of invasive carcinoma, loco-regional recurrence, overall survival (OS), and disease-free survival (DFS) were recorded and statistically analyzed. P<0.05 was determined as statistically significant. The study group consisted of 49 women with a mean age of 67.05±14.43 (range: 23-90) years. There was a significant association between the presence of invasive carcinoma and a mass lesion in the MRI (p=0.002). The frequency of sentinel lymph node (SLN) metastasis was significantly higher in patients with multicentric tumors (p=0.029; p<0.05). Locoregional recurrence and distant metastasis were significantly more frequent in patients with axillary involvement (p=0.0336; p<0.05). The mean DFS was 115.02±7.28 months, while the mean OS was 119.29±6.57 months. The presence of a mass lesion on MRI was determined to be significant in recognizing invasive carcinoma in MPD. The rate of SLN metastasis was higher in patients with multicentric tumors than in patients with unifocal tumors. Axillary involvement was associated with impaired DFS.

Differentiated thyroid carcinoma recurrence: patterns and participating factors

Background Surgery for recurrent differentiated thyroid carcinoma is technically difficult, is demanding, and carries a higher risk for complications than de novo cases, so understanding the precipitating factors and patterns of recurrence will help in practicing maneuvers that can help in decreasing the recurrence. In this study, we examined these factors and patterns of recurrence. Patients and method A total of 40 patients with recurrence after differentiated thyroid carcinoma surgery were subjected to redooperations after clinical evaluation and all needed preoperative investigations. Preoperative and operative data and postoperative surgical and pathological outcomes were collected and analyzed. Results Our results revealed that the size of the primary tumor had a negative or inverse significant relationship with time passed till occurrence of recurrence or relapse (P=0.044). However, postoperative radioactive iodine therapy, postoperative thyroxine replacement therapy, unifocal tumors, and total thyroidectomy in primary procedure all were associated with a wider range of recurrence time with a higher mean±SD but did not reach a statistically significant level. Central compartment lymph nodes are the most affected group (95%) followed by level IV nodes, which had a 100% correlation with central group, and all lateral groups summed 82.5%. Conclusion The primary tumor size has a significant inverse relationship with time till occurrence of relapse. However, other factors did not reach a statistically significant level. Central compartment lymph nodes, which are very difficult for safe dissection in recurrent cases, are the most affected group, confirming being the first echelon nodes followed by level IV nodes. Therefore, prophylactic routine meticulous central dissection in the primary cases is advised for being much easier and safer.

Is multifocality a risk factor in low-risk papillary thyroid cancer?

Multifocality in papillary thyroid cancer (PTC) is a common event, ranging from 18% to 87%. Additional multiple foci are frequently very small and generally detected in pathology specimens. The mechanisms of intrathyroidal spread, and its correlation with age, gender, tumour size, and lymph node metastases remain unclear. Moreover, studies assessing the prognostic impact of PTC multifocality have yielded non-univocal results. We aimed to evaluate the following: a) the histopathological and clinical characteristics associated with multifocal PTC; and b) the impact of multifocality on the long-term outcome. We analysed a consecutive series of 2814 PTC patients without evidence of microscopic extrathyroidal extension (T1a, T1b, and T2), all of whom had undergone total thyroidectomy and were followed-up (median 4.7 years) in our thyroid clinic. Females comprised 81.3% and males 18.7% (F/M = 4.4/1), with a median age at diagnosis of 45.0 years. Patients were subdivided into 2 groups: 72.7% unifocal tumour and 27.3% multifocal tumour. Post-surgical radioiodine ablation (RAI) (30-100 mCi of 131-I) was performed in 1425 (50.6%) patients. All patients were periodically followed with thyroglobulin and anti-thyroglobulin antibodies measurements and with neck ultrasonography under L-thyroxine therapy and subjected to additional radioiodine administration or another therapeutic measure if not cured. Patients in the multifocal group were older (median age 46.4 vs. 44.5 years, respectively, p < 0.05) and presented a lower F/M ratio (F/M = 3.7/1 and 4.7/1; p = 0.01). T1a and T1b tumours showed no significant difference in multifocality rate whereas T2 tumours were less frequently multifocal (14.2% vs. 10.9%, p < 0.05). Multifocal tumours were more frequent in N1b (11.3% vs. 7.8%, p < 0.01) and less frequent in Nx (50.5% vs. 56.8%, p < 0.01), with no difference between the N0 and N1a groups. The clinical outcome was similar in the 2 group of patients (88.2 % in the unifocal group vs. 90.2% in the multifocal group). Multifocality is more frequent in older and male patients, in smaller tumours, and in N1b. However, multifocality "per se" was not associated, in our study, with worse clinical outcome in PTC patients.

The Effect of Dynamic Contrast Magnetic Resonance Imaging (DCE-MRI) in the Diagnosis of Breast Cancer Cases

Aim: The aim of this study is to investigate the effect of dynamic contrast magnetic resonance imaging (DCE-MRI) in the diagnosis of breast cancer (BC) and to compare it with ultrasonography (USG).&#x0D; Materials and Methods: In our study, 78 patients who underwent preoperative DCE-MRI and USG in our diagnosis center in TRNC between 2009 and 2022 and were diagnosed with BC histopathologically were investigated retrospectively.Findings obtained according to the BI-RADS classification in both methods, detection of BC, detection of tumor foci (TF) in multiple tumors (multicentric and multifocal tumors) (MT), correct diagnosis rates(CDR)s in invasive lobular cancers (ILC) and invasive ductal cancers (IDC) were compared and the results were evaluated statistically.&#x0D; Results: The mean age of the ILC and MT cases was found to be significantly lower than the IDC and unifocal tumor(UF) cases (p

A study on the role of proliferative index marker Ki67 in breast carcinoma

Background. Breast cancer is the most common malignancy and the leading cause of cancer death among women worldwide. This study was conducted to establish early diagnosis and therapy, thus improving prognosis and overall survival rate. Objectives. To assess the levels of proliferation index marker Ki67 and hormone receptor status in patients with breast carcinoma and to correlate Ki67 with ER, PR, Her2neu status, as well as to correlate Ki67 and hormone receptor status with onco-pathological parameters. Materials and Methods. 392 patients diagnosed with breast carcinoma over a period of four years were included in the study. Data regarding patient’s identification, history, clinical finding, investigations and histopathological report were recorded in a specific proforma. Result. Breast cancer was seen to affect people in the older age group, and invasive ductal carcinoma of nonspecific type was the most common type. Most patients had unifocal tumor with grade 2 disease. Stage II disease was most common stage among the patients studied and Luminal B subtype was the predominant type of molecular subtype. Most of the patients were Ki67 positive, i.e., Ki67 &gt;14%. The correlation of Ki67 with estrogen receptor, progesterone receptor, tumor size, mitotic count, lymph node ratio, lymphovascular invasion and extra-nodal extension was found to be statistically significant. Conclusions. There exists a statistically significant, positive correlation between breast cancers, its onco-pathological parameters, proliferation index marker Ki67 and hormone receptor status. Therefore, the judicious use of these tests (Ki67 is an old marker of proliferation but not routinely used) will help in the early appropriate treatment of patients and contribute to the assessment of treatment response and prognosis.

Enrichment of “Cribriform” morphologies (intraductal and cribriform adenocarcinoma) and genomic alterations in radiorecurrent prostate cancer

AbstractLocally relapsed prostate cancer (PCa) after radiation therapy (RT) is associated with substantial morbidity and mortality. Morphological and molecular consequences that may contribute to RT resistance and local recurrence remain poorly understood. Locally recurrent PCa tissue from 53 patients with clinically localized PCa who failed with primary RT and subsequently underwent salvage radical prostatectomy (RP) was analyzed for tumor focality, clinicopathological, molecular, and genomic characteristics. Targeted next-generation sequencing with full exon coverage of 1,425 cancer-related genes was performed on 10 representative radiorecurrent PCas exhibiting no RT effect with matched adjacent benign prostate tissue. At RP, 37 (70%) of PCas had no RT effect with the following characteristics: grade group (GG) ≥ 3 (70%), unifocal tumor (75%), extraprostatic disease (78%), lymph node metastasis (8%), and “cribriform” morphologies (84%) [cribriform PCa (78%) or intraductal carcinoma (IDC-P) (61%)] at a median percentage of approximately 80% of tumor volume. In the setting of multifocal tumors (25%) at RP, the cribriform morphologies were restricted to index tumors. Of 32 patients with available pre-RT biopsy information, 16 had GG1 PCa, none had cribriform morphologies at baseline but 81% demonstrated cribriform morphologies at RP. Notable alterations detected in the sequenced tumors included: defects in DNA damage response and repair (DDR) genes (70%) (TP53, BRCA2, PALB2, ATR, POLQ), PTEN loss (50%), loss of 8p (80%), and gain of MYC (70%). The median tumor mutational burden was 4.18 mutations/Mb with a range of 2.16 to 31.86. Our findings suggest that most radiorecurrent PCas are enriched in cribriform morphologies with potentially targetable genomic alterations. Understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important to facilitate optimal patient management.

P11.22.A Prognostic and predictive relevance of immunohistochemically determined p53 mutation in glioblastoma

Abstract Background It can be expected that molecular biomarkers will increasingly affect clinical decisions and lead to the development of more personalized therapies in glioblastoma (GBM) in the future. In several other tumor entities TP53 gene mutation or p53 immunoreactivity (IR) serve as a prognostic marker, significantly affecting overall survival (OS) and progression-free survival (PFS). Such an association has not yet sufficiently been demonstrated in GBM. However, there are known prognostic markers in GBM, notably MGMT promotor methylation (mMGMT) which also serves as an important predictive marker leading to a better response to temozolomide chemotherapy. Our aim was to evaluate retrospectively if p53 mutation determined via immunohistochemistry (IHC) could act as a prognostic or predictive marker in GBM. Material and Methods Tumor samples of 195 treatment-naïve patients with IDHwt GBM that had been stained with the p53 antibody DO-7 were subdivided into 2 different groups by p53 IHC. Samples were considered as p53mut when strong p53 IR was detected in ≥10% of all tumor cells and as p53wt when in &amp;lt;10%. Treatment, further molecular and survival data were gathered retrospectively for all patients. Statistical analyses were performed with SPSS. Results The frequency of p53mut was 36.4% (71/195). p53mut tumors showed a significantly higher IR with Ki-67 proliferation marker (p=0.005) and p53wt seemed to be associated with multifocal primary tumor localization, though not statistically significant (p=0.107). There was no significant difference between p53wt and p53mut regarding gender, age, extent of resection, adjuvant therapy, occurrence of seizures, mMGMT or ATRX loss. The p53 status was not associated with OS or PFS. Factors that univariately led to significantly longer OS and PFS were younger age, unilateral or unifocal primary tumor localization, gross-total resection, higher Karnofsky Performance Status (KPS), mMGMT and adjuvant treatment via Stupp regimen instead of radiotherapy alone, the latter being significantly better than best supportive care. In multivariate survival analyses only age &amp;lt;65 years, the Stupp regimen more than radiotherapy alone and KPS ≥80% significantly prolonged both OS and PFS. Unifocal primary tumor localization led to longer OS and mMGMT led to longer PFS independently. The p53 status did not significantly affect the response to different adjuvant therapy regimens neither concerning OS nor PFS. Conclusion Based on our study, p53 IR has no prognostic or predictive significance in IDHwt GBM. There have been previous studies with similar and others with contradicting results. Remarkable is the discordance of the used IR thresholds between different studies. Further studies should aim to revalidate the staining threshold and improve the concordance between TP53 gene sequencing and p53 IHC in IDHwt GBM.

Number of Tumor Foci as a Risk Factor for Recurrence in Papillary Thyroid Carcinoma: Does It Improve Predictability?

Simple SummaryThyroid cancer is one of the most common cancers worldwide, and papillary thyroid carcinoma (PTC) comprises over 80% of all thyroid cancers. About 30% of patients with PTC have multifocality, which is useful for recurrence prediction. However, recent studies have suggested that the number of tumors, total tumor diameter, and bilaterality are more powerful predictors of recurrence than multifocality. Herein, we evaluated the effect of these factors on the predictability of recurrence in patients with PTC. Our study of 1288 patients confirmed that the number of tumors, total tumor diameter, and bilaterality could be independent predictors of recurrence even though they did not offer better predictability of recurrence than the prediction model using multifocality. Therefore, a simpler, multifocality-based prediction model would be sufficient for predicting recurrence in patients with PTC.Multifocality in papillary thyroid carcinoma (PTC) increases the risk of recurrence. Some recent studies have suggested that multifocality-related parameters, such as the number of tumor foci, total tumor diameter (TTD), and bilaterality, are more useful for predicting recurrence than multifocality. However, it is still unclear if these factors can improve the accuracy of the recurrence prediction model. Between 2012 and 2019, 1288 patients with PTC underwent total thyroidectomy at Ewha Womans University Medical Center. The 5-year disease-free survival rate was 91.2% in patients with >3 tumor foci, 95.1% with 3 foci, and 97.6% with 2 foci; conversely, those with a unifocal tumor showed a 5-year recurrence-free survival rate of 98.0%. Cox proportional hazards analysis indicated that the number of tumor foci (HR for >3 foci, 3.214; HR for 3 foci, 2.473), bilaterality (HR, 2.530), or TTD (HR for >3 cm, 5.359; HR for 2–3 cm, 3.584) could be an independent predictor of recurrence. However, models using the number of tumor foci, bilaterality, and TTD did not show better overall predictability of recurrence than models based on multifocality. In conclusion, a simpler prediction model based on multifocality may be sufficient.

Disparities in curative treatments and outcomes for early stage intrahepatic cholangiocarcinoma in the United States.

Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown. The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively. The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS. More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.

Analysis of factors influencing cervical lymph node metastasis of papillary thyroid carcinoma at each lateral level

ObjectiveTo analyze the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC) and its influence on the distribution of lymph node metastasis at each lateral level of the neck to guide precise treatment of the lateral area.MethodsThe clinicopathological data of patients with PTC initially diagnosed and treated at our hospital from February 2014 to September 2021 were collected; the metastatic status of each lateral level was recorded, and correlations were analyzed.ResultsA total of 203 patients were enrolled in this study. There were 67 males and 136 females, with an average age of 41.1 years. In the lateral cervical area, lymph node metastasis was found at level IIa in 81 patients (39.9%); level III, 171 patients (84.2%); level IV, 122 patients (60%); and level Vb, 18 patients (8.9%). Correlation analysis showed that age (r = 0.198, P < 0.01) and sex (r = 0.196, P < 0.01) were weakly correlated with the number of positive lymph nodes in the central region. The tumor size (r = 0.164, P < 0.05) was weakly correlated with lymph node metastasis at level IV. The presence of multiple tumor foci was weakly correlated with lymph node metastasis at level IIa (r = 0.163, P < 0.05) and Vb (r = 0.143, P < 0.05). The tumor location (r = − 0.168, P < 0.05) was weakly correlated with lymph node metastasis at level III. The number of positive lymph nodes in the central region (r = 0.189, P < 0.01) was weakly correlated with lymph node metastasis at level IV. Binary logistic regression analysis showed that the risk of metastasis of multifocal tumors was higher than that of unifocal tumors by 1.958 times at level IIa (P = 0.021, OR = 1.958) and 2.929 times at level Vb (P = 0.049, OR = 2.929). The higher the tumor was located, the higher the risk of metastasis at level III (P = 0.014, OR = 0.563). Every additional positive lymph node in the central region increased the risk of metastasis at level IV by 1.126 times (P = 0.009, OR = 1.126).ConclusionsFor patients with pathological evidence of lateral metastasis, standard dissection of level IIa through Vb is recommended; selective dissection requires careful consideration. Patients with multifocal tumors have a high risk of metastasis at levels IIa and Vb, which requires special attention during the operation.

Cytokeratin 5/6 expression in pT1 bladder cancer predicts intravesical recurrence in patients treated with bacillus Calmette–Guérin instillation

Bacillus Calmette-Guérin (BCG) instillation is the gold standard for the treatment of patients with pT1 bladder cancer but causes severe adverse effects. Few predictive factors have been established for intravesical recurrence and/or stage progression in bladder cancer. We analysed 138 patients who underwent transurethral resection of bladder tumour and were pathologically confirmed to have stage pT1 bladder cancer. Of these, 72 patients (52.2%) received intravesical BCG instillation, 12 patients (8.7%) demonstrated stage progression, and five patients (3.6%) died of the disease. The number of patients who received BCG instillation was more in the group with multifocal tumours than that in the group with unifocal tumours (p=0.0034). Among 53 patients (38.4%) who demonstrated cytokeratin 5/6 (CK5/6) expression, 15 patients (28.3%) showed CK5/6 expression in more than 10% of tumour cells and 38 patients (71.7%) showed CK5/6 expression in 1-10% of tumour cells. CK5/6 expression was observed in both invasive and non-invasive components in 15 patients (28.3%), only in invasive components in 30 patients (56.6%), and only in non-invasive components in eight patients (15.1%). Furthermore, CK5/6 expression was observed in tumour cells only in front of the invasive component and stroma in 24 patients. The proportion of CK5/6-expressing tumour cells in the invasive component was significantly higher than that in the non-invasive component (p<0.001). The follow-up period for patients who received BCG tended to be shorter than that in the non-BCG patients. The CK5/6-positive group displayed significantly shorter recurrence-free survival (RFS) than the CK5/6-negative group (p=0.0412). Importantly, CK5/6 expression was a significant predictive factor of inferior RFS in the BCG instillation group (p=0.0197). In contrast, CK5/6 expression was not significantly associated with RFS in the non-BCG instillation group (p=0.841). Thus, CK5/6 expression can be a predictive marker for RFS in patients with pT1 bladder cancer and can provide critical information for patient care.

PD14-07 LONG-TERM CYSTOSCOPY SURVEILLANCE OF PATIENTS WITH NON-RECURRING NMIBC: IDENTIFYING THE POINT OF DIMINISHING RETURNS

You have accessJournal of UrologyCME1 May 2022PD14-07 LONG-TERM CYSTOSCOPY SURVEILLANCE OF PATIENTS WITH NON-RECURRING NMIBC: IDENTIFYING THE POINT OF DIMINISHING RETURNS Daniel Ranti, Ralph Grauer, Yuanshuo Wang, Linda Dey, Lotta Renström, Gunnar Steinbeck, Abolfazl Hosseini, Peter Wiklund, Reza Mehrazin, John Sfakianos, and Nikhil Waingankar Daniel RantiDaniel Ranti More articles by this author , Ralph GrauerRalph Grauer More articles by this author , Yuanshuo WangYuanshuo Wang More articles by this author , Linda DeyLinda Dey More articles by this author , Lotta RenströmLotta Renström More articles by this author , Gunnar SteinbeckGunnar Steinbeck More articles by this author , Abolfazl HosseiniAbolfazl Hosseini More articles by this author , Peter WiklundPeter Wiklund More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , John SfakianosJohn Sfakianos More articles by this author , and Nikhil WaingankarNikhil Waingankar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002546.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-muscle invasive bladder cancer (NIMBC) is a heterogenous disease with high rates of disease recurrence up to 70%. The current AUA recommendations include initial close surveillance, followed by annual cystoscopies for 5 years, and thereafter based on shared decision making. In part due to the intense surveillance and cost of regular cystoscopies, bladder cancer has become the most expensive cancer to treat per capita in the United States. Approximately, 60% of costs are due to surveillance and treatment of recurrence. This abstract sought to analyze long-term recurrence of NMIBC to inform surveillance choices. METHODS: NMIBC patients were identified from a population-based dataset including all patients diagnosed with bladder cancer in Stockholm County between 1995-96. Demographics (gender, age at diagnosis) and clinical and treatment data (initial histology, tumor grade, tumor stage, focality, size, recurrence information, and mortality) were gathered. The starting point of our analysis was first diagnosis, and the stopping point was either date of recurrence or date of last follow-up. A random survival forest was run with tumor size, number of tumors, grade, stage, sex, and age at diagnosis as covariates. Risk groups were defined as the combination of grade (high, low) and stage (Tis, Ta, T1). A cumulative hazards curve for each risk group was created, and timepoint hazards were estimated via the derivative of the cumulative hazards. RESULTS: Median follow-up was 10 years, and median age at diagnosis was 71. There were 212 TaLG, 110 T1HG, 72 TaHG and 11 TisHG patients. Median time to recurrence was 283 days for TaLG; 190 days for TaHG; 119 days for T1HG; and 114 days for TisHG. Recurrence rates were 59.4% for TaLG, 66.7% for TaHG, 72.7% for T1HG and 27% for TisHG. Alive patients under surveillance without a recurrence were 9 for TisHG; 159 for TaLG; 57 for TaHG; and 84 for T1HG. Tumor number was the strongest predictor of recurrence (coefficient = 0.071) followed by tumor size (0.045). After 6 years, all patients showed low risk of recurrence. CONCLUSIONS: Tumor number was most predictive of recurrence, and after 6 years, all patients without disease carried low risk for recurrence. These findings suggest that surveillance cystoscopy, particularly in those with unifocal tumors and no recurrences, may be unnecessary beyond 6 years after diagnosis in select patients. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e258 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Ranti More articles by this author Ralph Grauer More articles by this author Yuanshuo Wang More articles by this author Linda Dey More articles by this author Lotta Renström More articles by this author Gunnar Steinbeck More articles by this author Abolfazl Hosseini More articles by this author Peter Wiklund More articles by this author Reza Mehrazin More articles by this author John Sfakianos More articles by this author Nikhil Waingankar More articles by this author Expand All Advertisement PDF DownloadLoading ...