Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Beyond the knife: strategic patient selection for cytoreductive nephrectomy.

PURPOSE OF REVIEW: To evaluate the current role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) within the context of evolving treatment paradigms, focusing on implications for patient selection. RECENT FINDINGS: Two randomized trials failed to show significant benefits from CN for intermediate and poor-risk patients undergoing targeted therapy. Despite this, subgroup analysis and retrospective data suggest potential benefits for a subset of good and intermediate-risk patients. Although currently used risk stratification tools guide CN eligibility, they have limitations, including, subjectivity, perioperative variability, and missing validation. Deferred CN may benefit patients responding to systemic treatment, whereas other patients may benefit from upfront CN. Emerging data supports the value of CN with immune checkpoint inhibitors (ICI) in selected patients, emphasizing the need for ongoing trials in the ICI era. SUMMARY: The role and timing of CN in mRCC have evolved across therapeutic eras. Although awaiting prospective evidence in the current era of ICI, CN still has a role in the therapeutic approach for a subset of patients. The decision to recommend CN must be personalized and involve multidisciplinary discussions considering both patient- and tumor-related factors.

Increase and Plateauing of Testicular Cancer Incidence in Austria-A Time Trend Analysis of the Past Four Decades.

Background: Testicular germ cell tumors (TGCTs) are the most common malignant tumors in young men. Despite considerable geographic, ethnic, and temporal variations in the incidence of TGCTs, without convincing explanation, incidence rates of TGCTs have been increasing in many countries since, at least, the mid-20th century. Objective: To investigate the incidence rates of TGCTs in Austria by analyzing data from the Austrian Cancer Registry. Design setting and participants: Available data between 1983 and 2018 were provided by the Austrian National Cancer Registry and analyzed retrospectively. Outcome measurements and statistical analysis: Germ cell tumors derived from germ cell neoplasia in situ were classified into seminomas and nonseminomas. Age-specific incidence rates and age-standardized rates were calculated. Annual percent changes (APCs) and average annual percent changes in incidence rates were determined to describe trends from 1983 to 2018. All statistical analyses were performed using SAS version 9.4 and joinpoint. Results and limitations: The study population consists of 11 705 patients diagnosed with TGCTs. The median age at diagnosis was 37.7 yr. The standardized incidence rate of TGCTs increased significantly (p < 0.0001) from 4.1 (3.4, 4.8) per 100 000 in 1983 to 8.7 (7.9, 9.6) per 100 000 in 2018 by an average APC of 1.74 (1.20, 2.29). The joinpoint regression revealed a change point in time trend in 1995 with an APC of 4.24 (2.77, 5.72) before 1995 and an APC of 0.47 (0.06, 0.89) thereafter. Incidence rates were about twice as high for seminomas as for nonseminomas. A trend analysis by age group showed that the highest TGCT incidence rate was observed among men aged 30-40 yr, with a steep increase before 1995. Conclusions: The incidence rate of TGCTs increased in Austria over the past decades and appears to have reached a plateau at a high level. A time trend analysis by age group for the overall incidence was highest in men aged 30-40 yr, with a steep increase before 1995. These data should lead to awareness campaigns and research to further investigate the causes of this development. Patient summary: We reviewed the data between 1983 and 2018 provided by the Austrian National Cancer Registry to analyze the incidence and incidence trend in testicular cancer. Testicular cancer shows an increasing incidence in Austria. The overall incidence was highest in men aged 30-40 yr, with a steep increase before 1995. The incidence appears to have reached a plateau at a high level in recent years.

Treatment of adrenocortical carcinoma: oncological and endocrine outcomes.

PURPOSE OF REVIEW: Adrenocortical carcinoma (ACC) is a rare, aggressive disease with a paucity of data and great variability between published studies regarding its treatment. This review provides information on current clinical management and oncological and endocrine outcomes. RECENT FINDINGS: Complete surgical resection is the only potentially curative treatment for adrenocortical carcinoma (ACC). Adjuvant mitotane treatment is recommended in patients with favourable/intermediate prognosis. As part of the endocrine follow-up, steroid hormones and thyroid hormones may be decreased or increased and may need to be substituted or suppressed. Recurrences are common. If the disease-free interval is more than 12 months, surgery is a treatment if complete resection is feasible. In advanced/metastatic ACC patients, the prognosis is poor. Mitotane monotherapy is only appropriate for patients with low tumour burden and indolent disease. Patients with unfavourable prognosis should be treated with aggressive cytotoxic therapy. Patients requiring third-line treatment should be considered for clinical trials. Immunotherapy and targeted therapy are currently being investigated, but have so far yielded only unsatisfactory results. SUMMARY: There is scarce evidence for the treatment of ACC, which often complicates clinical decision-making. Patients who progress on EDP-M should be treated in clinical trials.

The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy.

Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non-muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2-4N0M0 MIBC. Design setting and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19-0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84-3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66-3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). Conclusions: Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summary: We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non-muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.

Ischemic Priapism in a 12 Year Old Patient Associated With Coronavirus Disease 2019 (COVID-19): A Case Report.

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been associated with changes in blood coagulation resulting in increased incidence of venous thromboembolic events and coagulopathy. Moreover, single cases of ischemic priapism have been reported in adult patients with SARS-CoV-2 infection. In this report, we describe the case of ischemic priapism in a 12-year-old child with recent SARS- CoV-2 infection.

Salvage Radical Prostatectomy for Radio-Recurrent Prostate Cancer: An Updated Systematic Review of Oncologic, Histopathologic and Functional Outcomes and Predictors of Good Response.

A valid treatment option for recurrence after definite radiotherapy (RT) for localized prostate cancer (PC) is salvage radical prostatectomy (SRP). However, data on SRP are scarce, possibly resulting in an underutilization. A systematic review was performed using MEDLINE (Pubmed), Embase, and Web of Science databases including studies published between January 1980 and April 2020. Overall, 23 English language articles including a total number of 2323 patients were selected according to PRISMA criteria. The overall median follow-up was 37.5 months (IQR 35.5-52.5). Biochemical-recurrence (BCR)-free probability ranged from 34% to 83% at five years, respectively, and from 31% to 37% at 10 years. Cancer specific survival (CSS) and overall survival (OS) ranged from 88.7% to 98% and 64% to 95% at five years and from 72% to 83% and 65% to 72% at 10 years, respectively. Positive surgical margins ranged from 14% to 45.8% and pathologic organ-confined disease was reported from 20% to 57%. The rate of pathologic > T2-disease ranged from 37% to 80% and pN1 disease differed between 0% to 78.4%. Pre-SRP PSA, pre-SRP Gleason Score (GS), pathologic stage after SRP, and pathologic lymph node involvement seemed to be the strongest prognostic factors for good outcomes. SRP provides accurate histopathological and functional outcomes, as well as durable cancer control. Careful patient counseling in a shared decision-making process is recommended.

An up-to-date catalogue of urinary markers for the management of prostate cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Poor specificity and sensitivity of total PSA often results in over and sometimes underdetection/treatment. Therefore, more specific and sensitive biomarkers for the detection and monitoring especially of clinically significant PCa as well as treatment-specific markers are much sought after. In this field, urine has emerged as a promising noninvasive source of biomarkers. RECENT FINDINGS: RNA-based biomarkers are the most extensively studied type of urinary nucleic acids. ERG-Score/MiPS (Mi-Prostate Score) and SelectMDx might be considered as additional parameters together with clinical and imaging modalities to decrease unnecessary biopsies. miR Sentinel Tests could make it possible to accurately detect the presence of cancer and to distinguish low-grade from high-grade disease. In men with previous negative biopsies, PCA3 may suggest the need to repeat biopsy. SUMMARY: The definitive role of these markers and their clinical benefit needs future validation.

Secretion of severe acute respiratory syndrome coronavirus 2 in urine.

PURPOSE OF REVIEW: Despite the plethora of publications discussing the severe respiratory coronavirus 2 (SARS-CoV-2), evidence of viral secretion in urine is sparse. RECENT FINDINGS: We could identify 34 publications including a total of 2172 patients. Among those, 549 patients were tested for SARS-CoV-2 secretion in urine, which was detected in only 38 patients (6.9%). Within the seven studies displaying positive results, the majority of positive patients (86.8%) was from not yet peer-reviewed studies including weak data and heterogeneous techniques for sample testing. Furthermore, none of the studies available in the literature addressed the virulence of detected viral RNA in urine. SUMMARY: Overall, only seven studies were able to detect SARS-CoV-2 secretion in urine, all of them with a considerably low rate of positivity. However, these studies were of rather low quality considering their methodology. Despite this, as SARS-CoV-2 has been detected in urine, it is of importance to discuss safety and urinary hygiene protocols. Until further research provides valid data on viral shedding and virulence in urine, potential risk of transmission through urine cannot be ruled out. Therefore, safety and hygiene measures need to be discussed.

An overview of current and emerging diagnostic, staging and prognostic markers for prostate cancer.

INTRODUCTION: This manuscript aims to give an overview of current diagnostic, staging, and prognostic markers for prostate cancer (PCa) and discuss emerging approaches. The widespread use of PSA for early detection led to improved survival but at the cost of over-diagnosis, often associated with over-treatment and its adverse events. There is thus an unmet need for new markers to sustainably improve the diagnosis and risk assessment, thereby providing a more accurate treatment decision for each individual patient. AREAS COVERED: Promising new molecular serum (PSA, PHI, 4Kscore®), urine (Progensa®, SelectMDx®, MiPS) and tissue-based markers (Ki-67, Prolaris®, ConfirmMDx®, Oncotype Dx®, Decipher®, Promark®) will be discussed in this review. EXPERT OPINION: Over-diagnosis and difficulties in prognosticating clinical outcome among patients with similar histological and clinical parameters often lead to over- or under-treatment. New markers will probably be used with clinical and histopathological features as well as imaging diagnostics to capture the comprehensive biology and clinical behavior of PCa. New biomarkers open the avenue to avoid mpMRI with targeted biopsy in the future, thereby sparing risks and pitfalls associated with this approach. Before this utopia becomes reality, the panel of technologically complementary markers need to prove that they are better, cheaper, and faster than current strategies.

Poly(ADP-ribose) polymerase inhibitors in prostate and urothelial cancer.

PURPOSE OF REVIEW: The aim of this article is to give an overview of poly(ADP-ribose) polymerase inhibitors (PARPis) trials in prostate cancer and to discuss emerging approaches with potential future clinical implementation in both prostate and urothelial cancer. RECENT FINDINGS: PARPis are a class of drugs that can be applied for the treatment of homologous recombination repair (HRR)-deficient tumors. Tumors are potentially sensitive to PARPi harbor mutations in genes relevant for DNA damage repair, such as BRCA1/2 or ATM, which are present to a significant degree in metastatic prostate and urothelial cancer patients. Several PARPis have been successfully tested in clinical trials for HRR-deficient metastatic castration-resistant prostate cancer (mCRPC), and olaparib and rucaparib have recently received breakthrough approval in BRCA1/2 mutated mCRPC. Combination treatment of PARPis with androgen-receptor inhibitors or with checkpoint inhibitors and earlier frontline applications are currently being evaluated, and clinical trials enrolling bladder cancer (BCa) patients with HRR deficiency have recently been initiated. SUMMARY: Approximately 10% of mCRPC patients and 34% of metastatic BCa patients have tumors with HRR deficiency and may benefit from PARPi treatment. Correct identification of these patients as well as determining the most adequate time point for drug administration will be key to successful clinical implementation.

Surgical and Functional Outcome after Endoprosthetic Reconstruction in Patients with Osteosarcoma of the Humerus.

Endoprosthetic reconstruction (EPR) is the most widely used reconstruction technique after humeral osteosarcoma (OSA). Complications are common and function is often compromised due to the premise of wide resection. In the current study we evaluated (1) the risk of complications after resection and EPR; (2) the functional outcome and how it is influenced by the preservation/resection of deltoid muscle (DM), rotator cuff (RC), axillary nerve or the type of resection (intra-/extraarticular) and (3) if the preservation/resection of DM, RC, axillary nerve or the type of resection has a negative influence on the oncological outcome. We retrospectively evaluated data of 49 patients with humeral OSA. All patients underwent resection and EPR. Complication-free survival according to the ISOLS classification was estimated by a competing risk model. Functional outcome was evaluated by range of motion (ROM) in abduction and the MSTS score. Eleven patients (22%) had at least one complication. The estimated cumulative incidence for the first complication was 18% at one year, 23% at five years, and 28% at ten years, respectively. Soft tissue failure was the most common complication. ROM and MSTS scores were significantly higher in patients where DM and RC (p = 0.043/p = 0.046) and axillary nerve (p = 0.014/p = 0.021) could be preserved. Preservation of these structures had no negative influence on the surgical margins. In conclusion, EPR is a good treatment method with an acceptable complication rate. Preservation of the abductor mechanism, when possible in the setting of obtaining negative margins, provides superior functional outcome.