Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

A comparative study of AJCC and the modified staging system in pT2/pT3 penile squamous cell carcinoma - a validation on an external data set.

AIMS: The recent changes in the American Joint Commission on Cancer, 8th edition (AJCC-8E) pT2 and pT3 tumour definitions for penile cancer need robust validation studies. A recent study redefined and modified the pT2 and pT3 stages incorporating the histopathological variables (tumour grade, lymphovascular invasion, perineural invasion) similar to that used in the current AJCC-8E pT1 stage tumour subclassification. In this study, we validate and compare this proposed staging with the AJCC staging systems on an external data set. METHODS AND RESULTS: The data set from a previously published study was obtained. pT2 and pT3 stages were reconstructed as per AJCC 7th edition (AJCC-7E), AJCC-8E and the proposed staging. The staging systems were correlated with nodal metastasis, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). All systems were compared using receiver operating characteristic (ROC) curves. A total of 281 cases formed the study cohort. AJCC-8E (P = 0.031) and the proposed staging (P = 0.003) correlated with nodal metastasis on adjusted analysis, the latter with a better strength of association (AJCC-8E, γ = -0.471; proposed, γ = -0.625). On adjusted analysis, all the staging systems had a significant correlation with DFS, while only AJCC-8E and the proposed staging correlated with CSS and OS. On ROC curve analysis, the proposed staging had the highest area under the curve and was the only staging system to statistically correlate with all the outcome variables. CONCLUSIONS: The proposed staging for pT2/pT3 tumour stages in penile cancer may improve the prognostic and predictive ability.

Bladder preserving robotic pelvic exenteration for locally advanced rectal cancer-technique and short-term outcomes.

AIM: In selected patients with advanced rectal cancers involving the prostate or seminal vesicles, the bladder can be preserved to avoid the complications associated with an ileal conduit. The study was aimed at reviewing the technique and short-term outcomes of patients that underwent bladder sparing robotic pelvic exenteration with suprapubic cystostomy (SPC). METHODS: Case series of bladder preserving exenteration from a single tertiary care center. Technique for en-bloc prostatectomy with abdominoperineal resection is described. RESULTS: Five patients underwent bladder sparing robotic pelvic exenteration with SPC, all had R0 resections. Four patients had prostatic invasion and one patient had prostatic adenocarcinoma. Postoperative complications were seen in three patients of which two were re-explored. At a median follow-up of 10 months, two patients developed systemic relapses. There were no local recurrences. CONCLUSION: Robotic bladder sparing exenteration is technically feasible, provides acceptable short-term outcomes, and avoids complications of ileal conduit.

Blood testis barrier revisited-Analysis of post-chemotherapy germ cell tumor orchidectomy and retroperitoneal lymph node dissection specimens.

OBJECTIVE: To assess the response of chemotherapy on the primary tumor, compare it with the response in retroperitoneal disease, and study factors associated with pathological complete response. METHODS: We conducted a retrospective audit of all high inguinal orchidectomies (HIOs) performed after chemotherapy between 2012 and 2019 at a tertiary cancer center in India. Patient characteristics and histopathological response were extracted from electronic medical records, and predictors of testicular disease response were assessed. RESULTS: Of the 260 retroperitoneal lymph node dissections (RPLNDs) performed in the study period, 37 HIOs (14.23%) were carried out after chemotherapy. The median age of presentation was 28 years (16-41). Histopathology was divided into a viable tumor, mature teratoma, and necrosis/scarring. Residual disease was seen in 17 RPLND (46.0%) and 18 HIO (48.6%) specimens respectively. Of these 18, three patients had a residual viable tumor in the testis, and the remaining had a mature teratoma. Clinico-radiological assessment showed an average reduction of 61% in testicular disease size following chemotherapy. On orchidectomy histopathological assessment, the median tumor size was 9, 4, and 1.5 cm in specimens with a viable tumor, mature teratoma, and necrosis/scarring, respectively. CONCLUSIONS: A low threshold for upfront chemotherapy in patients with a high disease burden may be considered as tumors within the testis respond to chemotherapy in more than half of the patients. Discordance rates of residual cancer in RPLND and HIO specimens exist but post-chemotherapy tumor size in testis correlates with the presence of a residual viable tumor.

Primary extrarenal papillary renal cell carcinoma presenting as a neck mass.

Extrarenal primary renal cell carcinoma is an extremely rare entity with limited literature. Characteristic findings of renal cell carcinoma (RCC) at the metastatic site in the absence of a discrete radiological renal lesion can perplex both the clinician and pathologist. We report a case of metastatic primary extrarenal papillary RCC, who presented as a neck mass clinically and radiologically a paraaortic mass with normal bilateral native kidneys. The final diagnosis was aided by histopathological features, further confirmed by targeted immunohistochemical markers.

Perioperative therapy in muscle invasive bladder cancer.

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for muscle invasive bladder cancer (MIBC). The role of neoadjuvant and adjuvant therapy has evolved over the last 3-4 decades, and neoadjuvant chemotherapy (NACT) has now become the standard recommended treatment. However, there are many nuances to this and the utilization of chemotherapy has not been universal. The optimum chemotherapy regimen is still debated. Adjuvant radiation has a role in high-risk patients although not established and immunotherapy has shown promising results. We reviewed the evidence on NACT and adjuvant chemotherapy (ACT) regimens, NACT versus ACT, and the role of adjuvant radiotherapy and immunotherapy in MIBC.

Gastrointestinal stromal tumor presenting with lower urinary tract symptoms - A series of five cases with unusual clinical presentation.

Spindle cell tumors of the prostate are very uncommon and the majority involve the prostate secondarily from adjacent organs. Gastrointestinal stromal tumors (GISTs) are specific C-kit (CD 117) expressing mesenchymal tumors occurring in the gastrointestinal tract, commonly in the stomach and intestine; however, it is seldom seen involving the prostate. Although primary prostatic GISTs have been described, majority of them are secondary involvement from rectal GIST. The patient usually presents with urinary tract symptoms or prostate enlargement simulating a prostatic neoplasm. GIST as a differential diagnosis for prostatic mass is never thought of. We present a series of five cases of GIST arising from/involving the prostate mimicking a primary prostatic malignancy and the challenges associated with them for diagnosis and treatment.

Eosinophilic solid cystic renal cell carcinoma: A series of 3 cases elucidating the spectrum of morphological and clinical features of an emerging new entity.

Eosinophilic solid cystic renal cell carcinoma (ESC-RCC) is a recently described entity, which demonstrates distinct clinical, pathological and molecular features. We present a series of three cases, the first to be reported from the Indian subcontinent. All three patients were over 50 years of age; and presented with a large kidney mass. One patient had a locally advanced disease while the other two presented with metastases. Microscopic examination revealed a tumor displaying solid-cystic and/or papillary areas composed of clear as well as eosinophilic cells in all three cases. On immunohistochemistry, all the three cases showed a unique CK20+/α-methyl-acyl-CoA-racemase + immunophenotype. Melan-A was focally positive in Case 2. Cytokeratin 7 was focally but strongly positive in Case 3. The two patients with metastatic disease were diagnosed on core biopsies and were advised oral tyrosine kinase inhibitor therapy. The third patient underwent upfront radical nephrectomy. Due to its peculiar morphology and immunoprofile, the diagnosis of ESC-RCC can be confidently made even on a core biopsy. Most cases reported till date had an indolent course. The metastatic presentation in two of our patients emphasizes the need to gather further evidence to ascertain the biological behavior of this emerging entity.

Application and comparison of Fuhrman nuclear grading system with the novel tumor grading system for chromophobe renal cell carcinoma and its correlation with disease-specific events.

INTRODUCTION: The grading system of chromophobe renal cell carcinoma (ChRCC) is not well established. In this study, we aimed to compare the application of Fuhrman nuclear grade (FNG) with the novel chromophobe tumor grade (CTG). We also evaluated the correlation of these two grading systems with the clinical outcome. MATERIALS AND METHODS: Consecutive cases of ChRCC diagnosed on nephrectomy during 2005-2014 were identified. The clinical details of the patients were retrieved. Histopathology slides were reviewed and the nuclear grading was assigned using standard FNG and the CTG system. The CTG and FNG gradings were correlated with clinical outcome. RESULTS: A total of 80 cases were retrieved. Distribution of FNG was as follows: FNG-1, 1 (1.3%); FNG-2, 23 (28.3%); FNG-3, 44 (55.0%); and FNG-4, 12 (15%). CTG distribution was as follows: CTG-1, 48 (60.0%); CTG-2, 20 (25.0%); and CTG-3 12 (15.0%). Follow-up data was available in 46 cases; the median follow-up was 23.9 months (range 1-96.4 months). The median time to recurrence/metastasis was 17.2 months (range 3.2-31.2 months). Mean disease-free survival (DFS) was 68.5 months. Both CTG (P < 0.001) and FNG (P = 0.001) correlated with DFS; however, only CTG retained this significance when only the nonsarcomatous cases were analyzed. On receiver operating characteristics curve analysis, CTG had higher predictive accuracy for DFS for the entire group, while FNG lost the statistical significance when the nonsarcomatous cases were analyzed. CTG (P = 0.001) but not FNG (P = 0.106) correlated with the disease-specific adverse events in non-sarcomatous cases. CONCLUSIONS: It is possible to apply CTG in ChRCC. It is a better predictor of DFS and disease-specific adverse events. CTG is more appropriate and applicable than the FNG in grading ChRCC.

Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy.

BACKGROUND: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. METHODS: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. FINDINGS: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection. INTERPRETATION: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.

Management of clinically node-negative groin in patients with penile cancer.

Malignant penile neoplasms are commonly squamous etiology, with the inguinal nodes being the first echelon of spread. The disease spreads to the pelvic lymph nodes only after metastases to the groin nodes, and this is the most important prognostic factor in penile carcinoma. While treatment of penile carcinoma with proven metastases to the inguinal lymph nodes mandates ilioinguinal lymph node dissection, the treatment of patients with impalpable nodes is more controversial. Overtreatment leads to excessive treatment-related morbidity in these patients, while a wait-and-see policy runs the risk of patients presenting with inguinal and distant metastases, which would have been curable at presentation. Unfortunately, no single imaging modality has been proved to be convincingly superior in the staging, and hence, management of the clinically negative groin has been subject to debate. While some high volume centers have promoted the use of dynamic sentinel lymph node biopsy, others advocate the use of the modified inguinal lymph node template to stage the groin adequately. Newer techniques such as video endoscopic inguinal lymph node dissection have been introduced as an alternative to the original radical inguinal lymphadenectomy to reduce morbidity.

Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer.

BACKGROUND: Infertility is a known side-effect of oncotherapy in cancer survivors, and often compromises the quality of life. The present study was undertaken to detect very small embryonic-like stem cells (VSELs) in testicular biopsies from young adult survivors of childhood cancer who had azoospermia. VSELs have been earlier reported in human and mouse testes. They resist busulphan treatment in mice and potentially restore spermatogenesis when the somatic niche is restored by transplanting Sertoli or mesenchymal cells. VSELs also have the potential to differentiate into sperm in vitro. METHODS: The study had clearance from Institutional review board (IRB). Seven azoospermic survivors of childhood cancer were included in the study after obtaining their informed consent. Semen analysis was done to confirm azoospermia prior to inclusion in the study. Testicular biopsies were performed at the Uro-oncology Unit of the hospital and then used for various studies to detect VSELs. RESULTS: Hematoxylin and Eosin stained tubular sections confirmed azoospermia and smears revealed the presence of very small, spherical VSELs with high nucleo-cytoplasmic ratio, in addition to the Sertoli cells. Immuno-localization studies on testicular smears showed that the VSELs were CD133+/CD45-/LIN-, expressed nuclear OCT-4, STELLA and cell surface SSEA-4. Pluripotent transcripts Oct-4A, Nanog and Sox-2 were detected in azoospermic samples whereas marked reduction was observed in germ cell markers Oct-4 and Boule. CONCLUSIONS: The present study demonstrates the presence of pluripotent VSELs in the testicular biopsy of azoospermic adult survivors of childhood cancer. It is likely that these persisting VSELs can restore spermatogenesis as demonstrated in mice studies. Therefore, pilot studies need to be undertaken using autologous mesenchymal cells with a hope to restore testicular function and fertility in cancer survivors. The results of this study assume a great significance in the current era, where cryopreservation of testicular tissue in young pre-pubertal boys for restoring spermatogenesis in adulthood is still in experimental stages.

PRIMARY ADRENAL LYMPHOMA: A SINGLE-CENTER EXPERIENCE.

OBJECTIVE: To describe the clinical presentation, biochemistry, imaging features, and treatment outcome of patients with primary adrenal lymphoma (PAL) presenting to a single tertiary care center. METHODS: We performed a retrospective analysis of case records of 7 patients diagnosed with PAL between January 2011 and May 2014 at our institution in Mumbai, India. RESULTS: Median age of presentation in our series was 48 years (range, 41 to 60 years), with a male to female ratio of 6:1. Bilateral adrenal involvement was seen in 4 of 7 patients (58%). Adrenal insufficiency (AI) was seen in 3 of the 4 patients with bilateral involvement (75%). Computed tomography showed slight to moderate contrast enhancement of adrenal masses in 4 of 5 patients (80%). Diffuse, large, B-cell lymphoma (DLBCL) was the most common immunophenotype (85%). One patient died due to rapid disease progression even before starting chemotherapy. Six patients were treated with chemotherapy and/or external beam radiotherapy. After 1 year, 2 more patients had died, whereas 4 patients were in remission. CONCLUSION: PAL should always be considered in differential diagnosis of bilateral adrenal mass with AI. DLBCL is the most common histologic subtype of PAL. Despite treatment, long-term prognosis of PAL remains poor.

Delayed complication of pelvic lymphocele: Ileal conduit obstruction.

Radical cystectomy is the standard treatment for muscle invasive bladder cancer. Lymphocele is a common sequalae of pelvic lymphadenectomy. We report an unusual presentation of pelvic lymphocele developing after radical cystectomy reconstructed with an ileal conduit where the patient developed obstruction of the ileal conduit loop due to external pressure of the lymphocele. Catheter drainage of the conduit relieved the symptoms and a computerized tomography scan showed a large lymphocele causing acute angulation and resultant obstruction of the ileal conduit. The patient was treated with percutaneous drainage of the lymphocele and remains symptom-free on follow-up at 1 year.

Prognostic Significance of Lymph Node Density in Pathological Node Positive Urothelial Carcinoma of the Bladder -Upfront Surgery and Post Neoadjuvant Chemotherapy Cohorts.

AIM: To validate the role of lymph node density as a prognostic marker in patients undergoing primary surgery and postneoadjuvant therapy in pathological node-positive urothelial bladder carcinoma. MATERIALS AND METHODS: Retrospective analysis of 503 patients who underwent radical cystectomy from 2006 to 2019 for muscle-invasive urothelial bladder carcinoma, of which 152 patients with pathological node-positive disease were analyzed. Demographic details, pathological findings, treatment details, disease-free, and overall survival were documented. X tile program analysis was used to divide patients with positive lymph nodes into 3 groups: LD1: <= 7, LD2 :>7 to <15, LD3: >15, and the optimal cut-off value obtained was 15%. To evaluate the impact of lymph node ratio, patients with positive lymph nodes into 3 categories for each cut-off point estimation method, the application generates the histogram, Kaplan-Meier plot and calculates hazard ratio, confidence intervals and P-values. Univariate and multivariate cox regression analysis was done with a P-value of <.05, considered significant. RESULTS: One hundred fifty-two patients (30.2%) had pathological nodal metastasis, with 87 of them having perinodal extension. Ninety-six underwent primary surgery, and 56 were postneoadjuvant chemotherapy. The median follow-up was 55.42 months. 68 of the 152 node-positive patients died of the disease. Median number of lymph nodes removed was 17.11. Lymph node density divided into tertiles were LD1 <7%, LD2 7-<15%, LD3 >15% showed 5-year RFS 40.5%,29.3%, 22.6% and 5 year OS was 55.5%, 42.4%,32.1% respectively. Cox regression analysis showed that age less than 55 years ,higher tumor stage, lymphovascular invasion, and higher lymph node ratio were significant in univariate and multivariate analysis. The lymph node density cut-off value of 15% was substantial among node-positive patients (P = .027), and subgroup analysis in upfront surgery with the adjuvant treatment group and postneoadjuvant chemotherapy group was also significant (P =.021). CONCLUSION: Pathological higher T stage, Age <55 years, Lymphovascular invasion, adjuvant chemotherapy , adjuvant radiation treatment and lymph node density had prognostic significance in both cohorts of patients who underwent upfront surgery and neoadjuvant chemotherapy. Lymph node density cut-off value of <15% was prognostically significant.

Do Uro-Oncology Day Care Procedures Need to Be Differed during COVID-19 Pandemic?-An Experience from Tertiary Cancer Care Center.

Mahendra PalBackground The SARS-CoV-2 virus pandemic has affected millions all over the world in very short span and changed the way how health care system work across the globe. It is essential to continue cancer treatment in spite of such pandemics. Various recommendations were proposed for cancer management based on risk stratification, however, in urological malignancies, day care procedures (DCPs) are a part of complete spectrum of cancer care and standard operating procedures (SOPs) for day care procedures (DCPs)in oncology is lacking at present. Materials and Methods This is an institutional review board approved retrospective observational analytical study performed in tertiary cancer care center, with aim to assess the impact of COVID-19 on Uro-oncology day care procedures (U-DCPs)in terms of changes in appointments and actual U-DCPs performed, demographic changes such as sex ratio and age wise attendance in pre and post lockdown period and to provide a SOPs to accomplishU-DCPsefficiently in pandemics. Results There was 67.89% and 68.16% reduction in total numbers of appointment and performed U-DCPs. A statistically significant difference was found in cystoscopy, intravesicalinstallation and miscellaneous UDCPs. Overall, 4.45% reduction and 4.52% increase in male and female patients underwent UDCPs respectively, M:F ratio reduced from 3.58:1 to 2.79:1 and 30% to 50% reduction in overall patient statistics in post lockdown compare to pre lockdown procedures. For various age groups there was a statistically significant change in the number for males underwent cystoscopy in (p<0.001), Intravesical therapies (p<0.001) and miscellaneous procedures(p< 0.004). Conclusion We are now coming up to the fact that effective management of healthcare system during pandemics require establishment and effective implementation of standard protocols. Routine major urological surgical care is continued using a tiered standard of protocols (SOPs) and adequate precautions. This study may provide an insight into impact of COVID-19 on UDCPs and what precautions and strategies can be institutionalized so that the patients and the health care workers remain protected from contracting infection while in performing DCPs during pandemic or similar circumstances.