Role of lymphadenectomy during primary surgery for kidney cancer

Purpose of review Lymph node dissection (LND) during radical nephrectomy (RN) for renal cell carcinoma (RCC) is not considered as a standard. The emergence of robot-assisted surgery and effective immune checkpoint inhibitors (ICI) in recent years may change this and lymph node (LN) staging has become easier and has a clinical impact. In this review, we aimed to reconsider the role of LND today. Recent findings Although the extent of LND has still not been well established, removal of more LN seems to provide better oncologic outcomes for a select group of patients with high-risk factors such as clinical T3-4. Adjuvant therapy using pembrolizumab has been shown to improve disease free survival if complete resection of metastatic lesions as well as the primary site is obtained in combination. Robot assisted RN for localized RCC has been widespread and the studies regarding LND for RCC has been recently appeared. Summary The staging and surgical benefits and its extent of LND during RN for RCC remains unclear, but it is becoming increasingly important. Technologies that allow an easier LND and adjuvant ICI that improve survival in LN-positive patients are engaging the role of LND, a procedure that was needed, but almost never done, is now indicated sometimes. Now, the goal is to identify the clinical and molecular imaging tools that can help identify with sufficient accuracy who needs a LND and which LNs to remove in a targeted personalized approach

Metastasis-directed therapy in oligometastatic prostate cancer

Purpose of reviewTo summarize the recent findings on the subject of metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (omPCa).Recent findingsEvidence from two randomized clinical trials (RCTs) and a meta-analysis show favorable toxicity profiles, and the potential to delay androgen-deprivation therapy (ADT) for up to two years in nearly half of patients with metachronous hormone-sensitive omPCa. Another RCT showed promising results of MDT as treatment-escalation method combined with androgen receptor signaling inhibitors (ARSI) in first-line treatment for castration-resistant omPCa.Surveys by radiation oncologists and consensus guidelines advocate for MDT across various omPCa scenarios. Multiple single-arm trials present encouraging results; however, the evidence for the benefit of MDT is still weak requiring further investigation to assess its impact on pivotal endpoints, such as survival and quality of life.SummaryMDT is a promising approach in omPCa, and can be used to defer ADT in newly diagnosed metachronous omPCa patients, or to add to ARSI treatment at first diagnosis of castration-resistance. Ongoing prospective trials are needed to guide its optimal utilization in other settings, and patients should be informed about the evolving landscape of systemic therapies with proven survival benefits alongside MDT options

Імітація монаршної поведінки в “дивних” вчинках Богдана Хмельницького на початку 1649 р.

Увага до постаті Богдана Хмельницького як на фаховому, так і на дилетантському рівні не вщухає вже, навіть попри періодичні офіційні чи неофіційні заборони, протягом трьох з половиною століть. Політичні та ідеологічні чинники, як можна спостерігати останні півтора десятиліття в Україні та, частково, у Польщі, регулярно посилюють інтерес до біографії гетьмана, його вчинків, наслідків діяльності, супроводжуючись, як нерідко трапляється в аналогічних ситуаціях, створенням зі складної, протирічливой, трагічної постаті Б.Хмельницького національного ідола, усі дії якого набувають містичного, пророчого, апріорно історично-виправданого характреру. Концептуальні трагічні помилки, прорахунки, прояви некомпетентності, невиправданої навіть за поняттями тієї епохи жорстокості переважно «делікатно» замовчуються, у кращому разі – обмежуються легкими докорами, а здебільше - пояснюються «злочинною змовою» сучасників-поляків, які свідомо з метою дискредитації сфальсифікували вчинки гетьмана, перебільшивши закономірні для усіх війн трагічні складові україно-польської війни. Як не парадоксально, до сьогодні залишаються, на жаль, поодинокими спроби дати добре аргументоване, позбавлене соціологічних та психологічних штампів, пояснення тих чи інших вчинків Б.Хмельницького та його соратників (як, власне, і представників польського, татарського, російського та турецького таборів), яке б базувалося не на упередженому заздалегідь виправдальному чи звинувачувальному ставленні до подій середини XVII ст., а на підгрунті максимально повного врахування ментальних, поведінкових стереотипів доби. Ми маємо на увазі вишукано-резонансну рецензію Н.Яковенко на серію публікацій перш за все В.Смолія та В.Степанкова [17; див. також: 19], а також деяких інших авторів, зокрема О.Толочка [11] та автора цих рядків [2], присвячених політичній та духовній ситуації в Україні напередодні Хмельничини, українській національній революції та постаті Хмельницького. Для наших подальших роздумів немає особливої потреби здійснювати розлогий джерелознавчий та історіографічний аналіз, оскільки він, з одного боку, вимагає спеціальної концептуальної зосередженості, а з іншого - надалі ми будемо оперувати у необхідних випадках виключно загальновідомими, хрестоматійними аргументами, коли можна дозволити собі уникнути розлогих екскурсів щодо розгляду джерел та літератури. Зазначимо лише, що безпосередньо біографії Б.Хмельницького присвячена досить велика кількість робіт з різних наукових та ідеологічних таборів, серед яких в першу чергу слід назвати імена М.Грушевського, М.Кордуби, В.Липинського, І. Крип’якевича, В.Замлинського, Я.Дашкевича, В.Смолія, В.Степанкова, П.Гоя, Я.Федорука, В.Горобця, Т.Чухліба, В.Сергійчука, В.Серчика та багатьох інших. Події кінця 1648 – початку 1648 рр. з огляду на їх особливу роль в контексті подій українських визвольних змагань і які будуть нас цікавити в першу чергу

Current Disease Management of Primary Urethral Carcinoma

Context: Primary urethral cancer (PUC) is a rare cancer entity. Owing to the low incidence of this malignancy, the main body of literature consists mainly of case reports, making evidence-based management recommendations difficult. Objective: To review reported disease management strategies of PUC and their impact on oncological outcomes. Evidence acquisition: A systematic research was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement using Medline, Scopus, and Web of Science, to find studies of the past 10yr including ≥20 patients, and investigating treatment strategies and their impact on outcomes of the three most frequent histologies: urothelial carcinoma, adenocarcinoma, and squamous cell carcinoma. Evidence synthesis: In localized PUC, penis-sparing surgery can be performed in males, while in females, complete urethrectomy with surrounding tissue is advised to minimize recurrence due to positive margins. Radiotherapy (RT) has worse survival and recurrence rates, as well as more adverse effects, than surgery, limiting its use in genital-preserving therapy. Locally advanced PUC should be treated with multimodal therapy, as monotherapies result in inferior recurrence and survival rates. Extent of surgery is still undecided, favoring radical cyst(oprostat)ectomy with total urethrectomy (RCU). Lymph node involvement is a predictor of survival, highlighting the role of lymph node dissection for disease control and staging. RT can improve survival in combination with surgery and/or chemotherapy (CHT). Neoadjuvant platinum-based CHT can improve overall and recurrence-free survival. At recurrence, salvage therapy with surgery and/or CHT can improve survival. Superficial urothelial carcinoma of the prostatic urethra can be treated with transurethral resection. Stromal invasion often features concomitant bladder cancer with a poor prognosis and requires RCU with or without systemic preoperative CHT. Conclusions: PUC is a rare malignancy with an often poor natural course, requiring a stage- and gender-specific risk-based treatment strategy. The role of systematic perioperative CHT and the extent of surgery are becoming more important. Patient summary: In this review, we looked at the treatment options for primary urethral cancer. We found that while an organ-confined disease can be managed with local resection, growth beyond the organ border makes a combination of different treatment modalities, such as surgery and systematic chemotherapy, necessary to improve outcomes

Differences in the rate of lymph node invasion in men with clinically localized prostate cancer might be related to the continent of origin

OBJECTIVETo test whether the rate of lymph node invasion (LNI) differs between patients treated with radical prostatectomy (RP) at a European or a North American centre.PATIENTS AND METHODSIn all, 1385 men had RP with bilateral lymphadenectomy for clinically localized prostate cancer (587 from Dallas, Texas and 798 from Milan, Italy). Univariate and multivariate analyses focused on the association between the continent of origin and the rate of LNI, after controlling for prostate‐specific antigen (PSA) level, clinical stage, biopsy Gleason sum and the number of examined and removed lymph nodes.RESULTSEuropean men had higher PSA levels (9.1 vs 7.8 ng/mL), a higher proportion of palpable cancers (44.5 vs 32.8%), more nodes removed (mean 14.9 vs 7.8) and a higher rate of LNI (9.0% vs 1.2%; all differences P < 0.001). In multivariate analyses that controlled for PSA level and clinical variables, European men had an 8.9‐fold higher risk of LNI (P < 0.001) than their counterparts from the USA. Among preoperative variables, the continent of origin was the third most informative predictor of LNI (67.5%), after biopsy Gleason sum (74.3%) and the number of examined lymph nodes (71.0%), and improved the ability to predict LNI by 4.7%.CONCLUSIONMen treated at a European centre had a 7.3–8.9‐fold higher rate of LNI, despite adjusting for all clinical and pathological variables. It remains to be shown what predisposes European men to a higher rate of LNI

Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

Purpose To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. Materials and Methods Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. Results The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). Conclusions Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC

Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review

PURPOSE The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 – gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two – next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response

primary lymphomas of the genitourinary tract a population based study

Abstract Objective We performed a population-based analysis focusing on primary extranodal lymphoma of either testis, kidney, bladder or prostate (PGUL). Methods We identified all cases of localized testis, renal, bladder and prostate primary lymphomas (PL) versus primary testis, kidney, bladder and prostate cancers within the Surveillance, Epidemiology, and End Results database (1998–2015). Estimated annual proportion change methodology (EAPC), multivariable logistic regression models, cumulative incidence plots and multivariable competing risks regression models were used. Results The rates of testis-PL, renal-PL, bladder-PL and prostate-PL were 3.04%, 0.22%, 0.18% and 0.01%, respectively. Patients with PGUL were older and more frequently Caucasian. Annual rates significantly decreased for renal-PL (EAPC: −5.6%; p = 0.004) and prostate-PL (EAPC: −3.6%; p = 0.03). In multivariable logistic regression models, older ager independently predicted testis-PL (odds ratio [OR]: 16.4; p Conclusion PGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder. Relative to primary genitourinary tumors, PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL, even after adjustment for other-cause mortality