Grossing and reporting of radical prostatectomy specimens: An evidence-based approach.

Radical prostatectomy (RP) constitutes the primary treatment option for patients with clinically localized, biopsy-proven prostate cancer that requires local treatment with curative intent. Accurate reporting of radical prostatectomy specimens is required to guide further risk stratification and management of patients. Hence, for the handling and reporting of RP specimens, a standardized protocol should be followed. Many general pathologists may not be well-versed with the guidelines for the handling of radical prostatectomy specimens. This article discusses a detailed approach to grossing techniques, including specimen description, fixation requirements, gross cut-up, and reporting of the grade and stage of RP specimens. This will enable the pathologist to aid in multidisciplinary management.

Reporting Trends, Practices, and Resource Utilization in Neuroendocrine Tumors of the Prostate Gland: A Survey among Thirty-Nine Genitourinary Pathologists.

Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.

Impact of review of histopathology specimens at a tertiary oncology hospital in Eastern India-lessons learnt.

A central review of histopathology specimens at tertiary oncology hospitals is important for optimum patient care in the modern era of personalised medicine. The challenges of healthcare delivery and access to ancillary investigations faced by a pathologist from the Indian subcontinent are different from the western world. We undertook an audit to analyse the differences of opinion between the diagnosis offered at peripheral hospitals and a tertiary oncology hospital in Eastern India. By analysing the differences, common pitfalls and diagnostic discrepancies are identified which need to be addressed in future. This audit also highlights the need of setting up of tertiary oncology diagnostic centres to help both peripheral pathologists and cancer care clinicians like a hub and spoke model. This is most needed for haematopathology, soft tissue and gynaecologic oncology where the need of ancillary investigations is high.

Clinicopathological characteristics, prognostic factors and treatment outcomes of seminomatous germ cell tumours from a tertiary cancer centre in eastern India.

Background: . Seminomatous germ cell tumour (SGCT) is a rare but curable malignancy of young adults. The literature on management and outcome of SGCT is scarce from India. We report the demography and treatment outcome of SGCT at our centre. Methods: . We did a retrospective analysis of patients with SGCT treated from March 2011 to December 2018. Patients were staged appropriately with imaging, and pre- and postoperative tumour markers. High inguinal orchiectomy was performed in all with a testicular primary and received subsequent stage-adjusted adjuvant treatment. Patients were monitored for metabolic syndrome during follow-up after completion of treatment. Results: . We treated 85 patients with a median age of 37 (range 20-68) years. The primary site of the tumour was the testis in 80 (94%) and mediastinum in 5 (6%) patients. Cryptorchidism was present in 20 (25%) patients and testicular violation was present in 11 (14%) patients. Stage of the disease was I in 61, II in 13 and III in 6 patients. Adjuvant treatment in stage I disease was single-agent carbo-platin (area under the curve ×7) in 38 (62%), surveillance in 20 (33%) and radiotherapy in 3 (5%) patients. Five patients in the surveillance group relapsed. The 7-year mean (SD) relapse-free survival and overall survival were 83.1% (8%) and 98.7% (1.3%), respectively. Thirty-one patients (n = 52, 60%) had features of metabolic syndrome. Conclusions: . SGCTs have a high cure rate. Long-term follow-up is essential for monitoring toxic effects. Early diagnosis, avoidance of testicular violation and multidisciplinary management are the key features for better long-term outcome in SGCT.

Accuracy of MRI without intracavernosal prostaglandin E1 injection in staging, preoperative evaluation, and operative planning of penile cancer.

PURPOSE: To evaluate the performance of non-erectile MRI in staging and preoperative evaluation of penile carcinomas, compared to postoperative histopathology. METHODS: In this retrospective study, MRI scans of patients who had undergone surgery for penile carcinoma (n = 54) between January 2012 and April 2018 were read by two radiologists; and disagreement was solved in the presence of a third experienced radiologist. Data necessary for preoperative evaluation and staging were collected and compared with final postoperative histology and the type of surgery performed. All MRI had been performed without intracavernosal injection of prostaglandin E1 and with IV Gadolinium, as per local protocol. RESULTS: 54 patients were included in the study (mean age 57.52 ± 12.78). The number of patients with T1, T2, and T3 staging in histopathology were 32, 14, and 8. Moderate interobserver agreement was found for staging, disease-free penile length, and all subsites except urethra, which had weak agreement. Strong agreement of consensus MRI with final histopathological staging was found (49/54, weighted κ = 0.85), with high sensitivity and specificity. Sensitivity and specificity for involvement of corpus spongiosum, corpora cavernosa, and urethra were 95.5% and 93.8%, 87.5% and 97.8%, and 90.9% and 86.1%, respectively. Sensitivity (89.6%) and specificity (100%) of MRI for predicting adequate disease-free penile length were high. CONCLUSION: There were acceptable interobserver agreement and good diagnostic performance of MRI for staging and preoperative assessment without intracavernosal injection, especially for higher stages and higher degrees of invasion which require more extensive surgery.

Rare Case of Metastatic Pleomorphic Liposarcoma of Thigh Presenting as Ewing's Sarcoma.

Liposarcoma is an uncommon group of tumors in the pediatric population. Of the various known subtypes,pleomorphic liposarcoma is the most infrequent in children.We present the case of a 7-year old child coming to the radiology department for evaluation of a right knee swelling. Plain radiograph and corresponding MRI images showed features of primary bone tumor possibly Ewing's sarcoma in right distal femur. The child developed right shoulder pain and CT thorax abdomen was done which revealed retroperitoneal mass with hepatic and pulmonary metastases.Subsequent core needle biopsy from the femur confirmed metastatic liposarcoma with pleomorphic features, extremely rare in childhood.The very rare incidence of metastasis that too presenting as a common primary tumor the misdiagnosis of which could result in catastrophic fate. So it's of prime importance that clinicians should be aware of this entity. Keywords: FISH; liposarcoma; myxiod dedifferentiated liposarcoma; pleomorphic liposarcoma; softsarcoma.

Limitações à utilização da escala integrada de rastreio da propriocepção: estudo de viabilidade de um inquérito transversal / A limitation on the use of Integrated Proprioception Screening Scale: a feasibility cross-sectional survey study

INTRODUÇÃO: A propriocepção é essencial durante a implementação do movimento para atualizar os comandos de alimentação adiante resultantes da imagem visual e no planejamento e alteração de comandos motores gerados internamente. A escala integrada de rastreio da propriocepção (IPSS) avalia a propriocepção em vários domínios diferentes em pessoas com doença de Parkinson. OBJETIVOS: Determinar as limitações da IPSS enfrentadas por fisioterapeuta neurológico e voluntários geriátricos em ambientes clínicos. MATERIAIS E MÉTODOS: Dez Neuro-fisioterapeutas e trinta voluntários geriátricos de cada terapeuta foram recrutados para este estudo de viabilidade de pesquisa transversal. Os participantes foram selecionados de acordo com os critérios de inclusão. Os questionários foram projetados e criados para avaliar as dificuldades enfrentadas pelos terapeutas e voluntários geriátricos em termos de tempo necessário para a administração da escala, do nível de compreensão da escala e seus subníveis, e o esforço físico experimentado pelo terapeuta e voluntários geriátricos. A IPSS foi administrada pelo terapeuta. Goniômetro Universal, fita métrica e dispositivo de rastreamento de movimento foram usados durante a administração da IPSS. Após a administração, os questionários foram distribuídos e preenchidos por Neuro-fisioterapeutas e voluntários geriátricos. O teste Shapiro-Wilk foi usado para testar a normalidade, pois os dados eram inferiores a 50. RESULTADOS: Os dados foram expressos em mediana e intervalo. Skewness e Kurtosis também foram medidos. As variáveis foram expressas na forma de gráficos circulares. CONCLUSÃO: O estudo concluiu que o IPSS tem várias limitações como subjetivamente relatado pelos terapeutas e voluntários.

INTRODUCTION: Proprioception is essential during the movement implementation to update the feedforward commands resulting from the visual image and in planning and amendment of internally generated motor commands. The integrated proprioception screening scale (IPSS) assesses proprioception in different domains in people with Parkinson's disease. OBJECTIVES: To determine the limitations of IPSS faced by Neuro-physiotherapists and geriatric volunteers in clinical settings. MATERIALS AND METHODS: Ten Neuro-physiotherapists and thirty geriatric volunteers under each therapist were recruited for this feasibility cross-sectional survey study. Participants were selected according to the inclusion criteria. Questionnaires were designed and created to evaluate difficulties faced by therapists and geriatric volunteers in terms of time taken for the administration of the scale, level of understanding of the scale and its sublevels, and physical exertion experienced by both therapists and geriatric volunteers. The therapist administered IPSS. Universal Goniometer, measuring tape, and motion tracking device were used during the IPSS administration. After administration, Questionnaires were circulated and filled by Neuro-physiotherapists and geriatric volunteers. Shapiro-Wilk test was used for testing the normality, as data was less than 50. RESULTS: As the data follows not a normal distribution, data was expressed in median and range. Skewness and Kurtosis were also measured. Variables were expressed in the form of pie charts. CONCLUSION: The study concluded that IPSS has several limitations as subjectively reported by the therapists and volunteers.

Primary renal Ewing's sarcoma in an adult: an enigma.

OBJECTIVES: Extraskeletal Ewing's sarcoma is a rarity, with a renal primary in an adult, being even rarer. There is no consensus on the optimal imaging modality, as well as best therapeutic option, making them an enigma for clinicians. CASE PRESENTATION: We report the case of a 34-year-old lady, a known case of invasive lobular carcinoma of the left breast (ER,PR positive, Her2neu negative), having completed treatment in 2017, wherein, on an ultrasound evaluation for left flank pain, was incidentally found to have a left renal mass. A CT scan corroborated with the ultrasound, with an additional Level 1, left renal vein thrombus. She underwent an open left radical nephrectomy with renal vein thrombectomy. Histopathology of the resected tumor revealed features of Ewing's sarcoma of the kidney, confirmed by Fluorescent In Situ Hybridisation (FISH) and Immunohistochemistry (IHC). CONCLUSION: Primary renal Ewing's sarcoma in an adult is a rare occurrence, with no characteristic imaging features, and no universally accepted guideline based management protocols. Akin with standard Ewings sarcoma treatment strategies, a margin negative- radical nephrectomy with adjuvant chemotherapy, seems the most apt treatment strategy.

Not so 'rare'-an example of malignant melanoma in India: report from a tertiary cancer centre.

PURPOSE: Malignant melanoma (MM) is rare in India. Indian data on demography and treatment outcome on advanced MM is very limited in the literature. MATERIALS & METHODS: This is a retrospective study of advanced MM treated between January 2013 and December 2020. We evaluated the clinicopathologic features, mutational profiles, survival outcome and prognostic factors in advanced MM patients. RESULTS: Out of a total 460 patients, 185 (42%) had metastatic disease at presentation and were enrolled in this study with a median age of 63 years (range: 28-93) and male:female ratio of 94:91. The mucosal primary was predominant (n = 110, 59%) than cutaneous primary (38%) and anorectum was the most common site (n = 84, 45%). Tumour mutational analysis was performed in 65 (35%) patients. BRAF mutations were detected in 12 patients and KIT mutations in 7 patients. Thirteen patients didn't have any mutations and 22 patients had mutations other than KIT & BRAF. Only 59 (32%) patients took any systemic treatment - immune checkpoint inhibitors (ICIs) in 17, temozolomide in 18 and paclitaxel/carboplatin in 18, tyrosine kinase inhibitors in 6 patients. After a median follow-up of 26 months (95% confidence interval (CI): 11.6-not reached), median progression-free survival (PFS) was 7.1 months (95% CI: 4.4-9.1) and median overall survival was 14.8 months (95% CI: 7.7-18.2 months). The use of ICI emerged as an only significant good prognostic factor (p ≤ 0.001) for PFS, on multivariate analysis. CONCLUSION: Mucosal origin was more common than cutaneous primary with anorectum being the most common site. BRAF mutation was less as compared to published literature. Very few patients received systemic therapy and the use of ICI showed superior PFS.

Gross reporting of adult kidney tumor specimens: A comprehensive evidence-based review.

Renal tumors comprise a wide spectrum of benign and malignant tumors. The important prognostic factors in renal cell carcinoma include pathological stage, tumor grade, morphological type, sarcomatoid/rhabdoid differentiation, and tumor necrosis. Therefore, the pathologist needs to be fully aware of how to gross nephrectomy specimens to be able to accurately provide the above prognostic information while reporting adult kidney tumors. With the advent of nephron-sparing surgeries, due diligence should be exercised to assess and sample the parenchymal surgical margin. This article discusses the approach to grossing nephrectomy specimens, elaborates the significance of every step, and also sheds light on the importance of clinical and radiological information in providing a holistic approach to the diagnosis and staging of adult renal tumors.

Epidermal growth factor receptor mutation status in pulmonary adenocarcinoma: Multi-institutional data discussion at national conference of "Lung Cancer Management in Indian context".

The presence of activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in adenocarcinomas of lung confers sensitivity to tyrosine kinase inhibitor therapy. The prevalence of EGFR mutations varies among different ethnicities and demographic profile. This multi-institutional data was compiled to determine the EGFR mutation status in Indians patients with lung adenocarcinoma. Cohorts represented by 4 tertiary care hospitals participated in data discussion at a national conference entitled as 'Lung Cancer Management in Indian Context'. The clinicopathologic data and EGFR mutation rate in the patients of lung adenocarcinoma screened in these cohorts were collected and analyzed. The sample types included both surgical and cytological specimens. A variety of methods were used including immunohistochemistry, polymerase chain reaction, Sanger sequencing and next generation sequencing. A total of 3436 cases of treatment naïve lung adenocarcinoma were tested for EGFR mutations. The overall frequency of EGFR mutations observed was 30.03%. The most common baseline mutation detected was exon 19 deletion followed by L858R point mutation in exon 21. Dual mutations were observed in 6.5% of cases and were predominantly combinations of exon 19 deletion and T790M point mutation in exon 20. Incidence of EGFR mutations was higher among females and non-smokers diagnosed with lung adenocarcinomas. The most common histology in EGFR mutant cases was acinar predominant adenocarcinomas. With nearly one-third of Indian patients with lung adenocarcinoma harboring EGFR mutations, routine testing for these mutations is important to get the benefit of targeted therapy.

Next generation sequencing in lung cancer: An initial experience from India.

INTRODUCTION: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients. MATERIAL AND METHOD: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform. RESULTS: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, n = 58) followed by EGFR (32.4%, n = 50), KRAS (18.18%, n = 28), ERBB2 (3.2%, n = 5), BRAF (1.94%, n = 3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%). CONCLUSION: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers.

Grossing and reporting of testicular tumor specimens : An evidence-based approach.

The majority of testicular tumors are germ cell tumors (GCTs), but there are numerous other types, making testicular tumors one of the most diverse areas of human pathology, despite their relative rarity. Testicular tumors are usually diagnosed only after radical surgery, as biopsies are not performed. Further management of the patient is dependent on the diagnosis at microscopy, which itself is based on the sections taken at the time of grossing the specimen. Many pathologists often aren't well versed with guidelines for handling of orchiectomy specimens and for microscopy. This article discusses, in detail, the approach to grossing of a testicular tumor specimen and elaborates of the reasons as to why we do what we do at the initial "cut-up". It explains the logic behind the reporting guidelines for testicular tumors and offer a clinical primer to the pathologist as to why we do what we do while grossing testicular tumor specimens.

Presentation and Management of Dermatofibrosarcoma Protuberans: a Single Center Protocol.

Dermatofibrosarcoma protuberans (DFSP) is a slow growing dermal tumor with a very low metastatic potential but with significant subclinical extension and capacity for local destruction with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision. We reviewed the excision technique along with the recurrence rates at a tertiary care center in eastern India. This study is a retrospective review of patients with DFSP from June 2011 to September 2018. Patients had initial wide excision using 2-3 cm margins with primary closure or reconstructive procedure; re-excision was done for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of excisions, reconstruction methods, radiation, and outcomes. A total of 31 patients with DFSP (15 males, 16 females), median age 41 years (range 14-82), were treated. Locations were extremities (13), trunk (12), and head and neck (06). The median number of excisions to achieve negative margins was 1 (range 1-3). Closure techniques included primary closure (13; 42%), tissue flaps (13; 42%), and skin grafting (05; 16%). There were 11 patients who received postoperative radiation, 4 for positive margins after maximal surgical excision. At a median follow-up of 24 months (range 1-72), 2 patients (6.5%) recurred locally, and 1 patient (3.2%) had lung metastasis. Using a standardized surgical approach including meticulous pathologic evaluation of margins, low recurrence rate (10%) was achieved with adequate margins (2-3 cm).

Clinicopathological characteristics and treatment outcome in small cell lung cancer: A single institutional experience from India.

BACKGROUND AND OBJECTIVES: Small cell lung cancer (SCLC) constitutes 14%-20% of all lung cancers. Clinical data on SCLC are scarce in literature. To report clinical features and treatment outcome of SCLC treated at our center. MATERIALS AND METHODS: This is a single institutional data review of SCLC patients treated between June 2011 and December 2018. Patients were staged as either localized or extensive disease after appropriate staging work-up. Patients with localized disease were treated with concurrent chemoradiation with platinum-based chemotherapy. Those with extensive disease were treated with platinum based palliative chemotherapy. Clinicopathological characteristics, treatment details, and outcome were recorded in this study. Patients who received at least one cycle of chemotherapy were included for survival analysis as intent-to-treat analysis. RESULTS: A total of 181 were patients registered with a median age of 62 years (range: 35-86 years) and male: female ratio of 166:15. Eighty-seven percent (n = 157) of patients had smoking history and 15% (n = 28) of patients had symptom of superior vena cava obstruction at baseline. Twenty-seven (15%) patients had localized disease at presentation. One hundred and twenty (66%) patients took systemic chemotherapy. Chemotherapy regimen was carboplatin only in 9 (7%), etoposide-carboplatin in 54 (45%), and cisplatin-etoposide in 57 (48%). Patients received median cycle number of 6 (range: 1-6). Of the evaluable 87 (73%) patients, initial response was complete response in 4, partial response in 57, stable disease in 20, and progressive disease in 6. Twenty patients received second-line chemotherapy at time of disease progression. After a median follow-up of 8.8 months (range: 0.3-46.1), median progression-free survival (PFS) of the whole population was 9.3 months. CONCLUSIONS: Small cell carcinoma in our series had a high incidence of advanced stage (85%) and 13% of patients were nonsmoker. Only 66% of patients received palliative chemotherapy and achieved high disease control rate (>75%) in the evaluable patients with median PFS of 9.3 months.

Prostate-specific Membrane Antigen-expressing Hepatic Lesion: Metastatic or Hepatocellular Carcinoma.

Prostate-specific membrane antigen (PSMA) is a glycosylated type-II transmembrane protein highly expressed in certain tumor cells. It has emerged as a novel radiotracer for evaluation of prostate cancer. Increased PSMA expression in isolated liver lesion is a diagnostic challenge. Solitary liver metastasis from prostate cancer is rare. On the other hand, PSMA avid primary hepatocellular carcinoma (HCC) has been reported in literature. We report a case of PSMA expressing atypical HCC with normal alphafeto protein (AFP) and raised prostate specific antigen (PSA).

Inflammatory Pseudotumor of the Renal Pelvis.

Background: Inflammatory pseudotumor of the kidney is a rare disease of unknown etiology. There are no specific clinical or radiologic findings. The lesion can mimic renal cell carcinoma or transitional cell carcinoma depending on the site of involvement. These tumors, if diagnosed correctly, may respond to medical management. We present a case in which an inflammatory pseudotumor of the renal pelvis was misdiagnosed as a transitional cell carcinoma and unwarranted surgical intervention was performed. Case Presentation: A 39-year-old man presented with left flank pain and gross hematuria. On MRI, there was a hypointense 2.4 × 1.8 cm lesion involving the left renal pelvis. The urine cytology and biopsy of the lesion were inconclusive. On follow-up cans the lesion increased in size and patient had repeated hematuria. The lesion was clinically presumed to be a transitional cell carcinoma of the left renal pelvis. A laparoscopic left side nephroureterectomy along with bladder cuff excision and para-aortic lymphadenectomy was performed. The histology report revealed the lesion to be inflammatory pseudotumor of the renal pelvis. Conclusion: Inflammatory pseudotumor should always be considered in differential diagnosis of pelvic tumors, especially when image findings and biopsies are inconclusive.

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data.

OBJECTIVE: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT. METHODS: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS). RESULTS: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P < 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027). CONCLUSIONS: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.