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Introduction & Objectives: Bladder preservation is routinely used as an alternative to radical cystectomy in the UK and is becoming more accepted elsewhere globally. The gold standard is for patients to receive radiotherapy with a radiosensitiser most commonly concurrent chemotherapy e.g. 5FU/mitomycin C, gemcitabine or cisplatin. Patients with poor performance status or comorbidities may be unable to be offered concurrent treatment with chemotherapy but alternative treatment with concurrent carbogen +/- nicotinamide as a hypoxic modifier may be of benefit. Our aim therefore was to retrospectively review patients with bladder TCC treated with radical radiotherapy alone in the last 5 years who may have benefited from carbogen +/- nicotinamide radiosensitisation at a large cancer centre in the north of England. Material(s) and Method(s): In this single institution retrospective case note review, electronic records were reviewed for 175 patients who had received radiotherapy to the bladder for TCC between 2017-2022. Patients who had radical radiotherapy (RT) alone without radiosensitisation were scrutinised to ascertain whether they would have been candidates for carbogen and nicotinamide using the inclusion/exclusion criteria previously defined in the Bladder Carbogen Nicotinamide (BCON) Randomised Phase 3 trial. Result(s): We analysed 175 patients. Of these, 133 received had radical RT without radiosensitisation. The most common reason for not offering radiosensitisation was the presence of co-morbidities (27.8%). Of interest, the proportion of patients having chemotherapy radiosensitisation did not change after COVID19 in March 2020 (21.5% pre- vs 27.5% post;p=0.32 chi2). Conversely, the proportion of patients receiving neo-adjuvant chemotherapy reduced though failed to reach significance (12.6% pre- vs 5% post;p=0.08 chi2). After review of the notes and criteria from the original BCON trial, 106 patients (79.6%) could have benefited from carbogen +/- nicotinamide. Of these, 14 patients (13.2%) could have been offered carbogen alone due to poor renal function. The most common reason for not being eligible for BCON was respiratory disease with reduced respiratory drive (44%). Conclusion(s): The National Institute for Health and Care Excellence (NICE) state that all radical RT for bladder TCC should be with a radiosensitiser. Due to logistical and departmental issues, the BCON regimen is not currently offered as a standard alternative to radiosensitisation with chemotherapy. BCON has been demonstrated to be tolerable and, whilst updated follow-up data failed to demonstrate statistical significance for overall survival (OS), meta-analysis of hypoxia modification has shown significant improvement in OS compared to RT alone. Hypoxia modification with carbogen +/- nicotinamide should be considered for all patients unsuitable for chemotherapy radiosensitisation.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Sarcomatoid urothelial carcinoma is a rare and aggressive variant. Serum beta-hCG levels are used as a tumor marker in gestational trophoblastic diseases and germ cell tumors, but may also be elevated in high-grade bladder cancers. Here, we report two urothelial carcinoma cases with sarcomatoid differentiation that relapsed early after surgery with elevated serum beta-hCG levels. The first case was a 65-year-old female and the second case was a 67-year-old man with sarcomatoid urothelial carcinoma located in the ureter and renal pelvicalyceal system, both of them relapsed with elevated beta-hCG serum level to 146.8 mIU/ mL and 242 mIU/mL, respectively. They died a few months after initial diagnosis;4.9 and 2.5 months respectively. Both sarcomatoid variant and beta-hCG expression were associated with poor prognosis and advanced stage. However, beta-hCG is not used as a tumor marker in urinary tract cancers yet, and its relationship with variant pathologies has not been clarified. We need multi-centered studies to reveal this relationship.Copyright © 2023, Derman Medical Publishing. All rights reserved.
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Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Method(s): We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Result(s): Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/ etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1+/-10+/-9/L vs 2.90+/-10+/-9/L, p<0.0001);and neutropenia rates were markedly lower (2% vs. 93%, P=,0.0001). Hospital admission rates were significantly lower in G-CSF users compared to nonusers (19% vs. 69%, P,0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusion(s): During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.
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Introduction & Objectives: Urothelial cancer is a lethal disease with a rising incidence. The current imaging modalities for staging, either CT of the chest, abdomen and pelvis or FDG PET/CT, have issues. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG PET is predominantly renally excreted and has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Utilizing 89Zr-TLX250, which is predominantly hepatically cleared, may improve imaging in these scenarios. The aim of this study is to explore the feasibility, safety, and utility of Zirconium-89-Girentuximab (89Zr-TLX250) PET/CT in the accurate staging of bladder and urothelial cancer as compared to FDG PET. Material(s) and Method(s): ZipUp is single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. Following Ethical approval (HREC ID: RGS3940), all participants undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison (Figure 1. Trial Schema). This trial aims to recruit 10 participants undergoing pre-operative staging prior to planned cystectomy and 10 participants with known metastatic disease. The primary endpoint is feasibility defined by the ability to recruit to the target sample size within the study duration. Secondary endpoints are safety, tolerability and sensitivity/specificity in detecting lymph node metastases (pre-cystectomy group) compared with FDG PET/CT. Result(s): Since May 2021, 15 patients consented to participate, but 2 patients subsequently withdrew. 7 patients did not proceed to dose administration and imaging due to COVID-19 pandemic related supply issues of IMP which would have delayed initiation of treatment. 6 patients have been enrolled with imaging performed. . 5 pre-cystectomy staging group . 1 metastatic group Conclusion(s): If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. [Figure presented]Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Background: COVID-19 vaccination recommendations for cancer patients (pts) are similar to the general population. The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is the occurrence of immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. This retrospective study examined the incidence of severe irAEs in pts with bladder urothelial cancer (UC) treated with CPI therapy who received concurrent vaccinations against Sars-CoV-2. Method(s): Following IRB approval, UC pts who received any approved CPI treatment since FDA authorization of the first COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received 1 or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (defined as one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation. Data was analyzed using descriptive statistics. Result(s): Forty pts were included in our analysis with a median age of 72.5 years (IQR: 66.0-79.2);82% pts were male. At the time of vaccination, 37 pts (92.5%) received CPI monotherapy, 2 pts (5.0%) received combination (combo) CPI therapy, and 1 pt (2.5%) received combo platinum-based chemotherapy and CPI. The vaccine manufacturer was Pfizer Bio-NTech in 22 pts (55.0%), Moderna in 17 pts (42.5%), and Johnson and Johnson in 1 pt (2.5%). Number of vaccinations received was>/= 3 in 27 pts, 2 in 11 pts, and 1 in 2 pts. Six pts (15.0%) experienced severe irAEs following vaccination, including nephritis, colitis, pneumonitis, DKA, and infusion-related reaction. Rates of severe irAEs were 16.2% (6/37) with CPI monotherapy, no severe irAEs occurred in the combo CPI and combo CPI-chemo groups. Severe irAEs occurred after the first vaccine dose in 1 pt (16.7%), second dose in 3 pts (50.0%), and third dose in 2 pts (33.3%) pts. The median time between CPI treatment and vaccination in this group was 22.0 days (IQR: 15.8-36.5. Hospitalization was required for all 6 patients (100%). Three pts (50.0%) required immunosuppressive therapy with a median therapy duration of 64.0 days (IQR 47.0-83.5). Five pts (83.3%) discontinued CPI therapy following severe irAEs. Conclusion(s): In this retrospective study, we observed a 15% rate severe irAE in UC pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI.
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Case report - Introduction: This case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises. During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with highdose steroids. Risks of infection (common and atypical) need to be considered. Case report - Case description: A is a 67-year-old female nonsmoker diagnosed with seropositive rheumatoid arthritis (RF, anti - CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016. In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen. Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018. Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5-10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime. Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment. Case report - Discussion: Cancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancer Whilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression. Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignancy undergoing chemotherapy due to a theo etical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters. Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life. Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations. Case report - Key learning points: . Primary peritoneal cancer is uncommon and can present as an incidental finding . Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life . Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers - lack of "named" providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult.
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Three new drugs, all based on messenger RNA or small interfering RNA technology, represented a major therapeutic advance in 2021. But the bigger picture is that most of the new authorisations that advanced patient care were adaptations of existing drugs. And that more than half of this year's new authorisations were not advances, and in fact about one-tenth represented a step backwards compared to existing options.
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This report presents the case of a 65-year-old male diagnosed with two concomitant cancers: transitional cell carcinoma within bladder diverticulum (G3, pTa) and prostate adenocarcinoma cT2bN0M0 (Gleason 7 (3+4)). Due to specific location of the bladder cancer (within diverticulum) and the concomitant prostate adenocarcinoma, we decided to perform a single surgery to treat both diseases: 3D Laparoscopic cystoprostatectomy with pelvic lymphadenectomy and ileal conduit. Diverticulum bladder urothelial carcinoma in situ (pTisN0MxL0V0R0) and acinar prostate adenocarcinoma Gleason 7 (3+4) (pT2bN0MxL0V0R0), both with surgical negative margins, and 21 negative lymph nodes were reported in pathology. Seric PSA follow-up was undetectable 1 month after surgery. Clinical and therapeutic management of this disease are also discussed.
ABSTRACT
Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COVID-19 pandemic. Methods: We evaluated screening, novel diagnoses, and surgical management modalities of prostate cancer (PCa), urothelial carcinoma (UC) and renal cell carcinoma (RCC) within Massachusetts General Brigham, the largest healthcare system in the Northeastern United States, over four 3-month time periods during the pandemic (March 2020- March 2021). The percentage change in screening, diagnoses and management modalities during pandemic periods as compared to the immediate pre-pandemic period (December 2019-March 2020) was calculated as (Nperiod - Ncontrol)/Ncontrol. The difference in "predicted" versus "observed" diagnoses in each pandemic period was compared to the average of the four preceding 3-month periods (March 2019-March 2020) to account for seasonal variation. Results: The first pandemic peak (March-June 2020) was associated with a significant decline across screening, diagnosis and treatment, ranging from -15.7 to -64.8%, followed by a progressive recovery, ranging from -5.9 to +25.1% in the latest period (December 2020-March 2021) (Table). Although 725 diagnoses were "missed" between March and June 2020 as compared to the previous 12 months, 971 diagnoses were "recovered" between June 2020 and March 2021. Conclusions: A substantial disruption in the screening, diagnosis and treatment of GU malignancies was observed early in the pandemic, followed by a progressive rebound and recovery. The highest declines were observed for PSA screening, and the lowest for cystectomy procedures, reflecting triaging of care based on severity during the pandemic.
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Despite the many challenges faced in 2020, we have seen impressive progress in many areas of cancer research. Twenty-one novel oncology drugs were approved by the U.S. Food and Drug Administration (FDA). Although cancer is one of the major public health problems worldwide, cancer mortality projections for 2021 confirm the persistent declines in cancer mortality in EU and US for many specific cancers. The breast cancer treatment landscape has evolved in the past year and several new drugs approved in 2020 as antibody drugs conjugates (ADC) sacituzumab in TNBC and fam-trastuzumab deruxtecan-nxki (T-DXd) in metastatic HER2 positive BC, as well as tucatinib, a small kinase inhibitor. A few very important clinical trial /RxPONDER, ADAPT, PRIME II/ presented last year support de-escalation of adjuvant chemotherapy and radiation, sparing patients from some of the side effects that can accompany treatments. In ovarian cancer five-year follow-up data from the SOLO-1 trial continue to show progression-free survival benefit of olaparib as maintenance therapy following platinum-based chemotherapy in the frontline setting. In the final analysis of SOLO-2 trial, maintenance olaparib provided an improvement of 12.9 months in median OS vs placebo in women with relapsed BRCA-related ovarian cancer who had responded to their most recent platinum-based chemotherapy after having received at least one more line of chemotherapy.In 2020 first new treatment for hepatocellular carcinoma approved in more than ten years according to the data from phase III IMbrave 150 trial. In that study, which includes 501 patients the combination of atezolizumab and bevacizumab provides the longest survival seen in a front-line phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC.In the field of thoracic oncology there were some very important news in 2020, potentially practice changing. Osimertinib, next generation EGFR-TKI, standard first line therapy in metastatic EGFR-mutated advanced NSCLC was successfully used, in ADAURA study, in adjuvant setting vs placebo (planned treatment duration three years), in resected NSCLC patients, stage IB-IIIA. Patients might had adjuvant chemotherapy also, and there was no outcome differences between these two groups. Overall, there was a 79% reduction in the risk of disease recurrence or death (DFS HR was 0.21, p<0.0001). Lorlatinib is the third generation of ALKinhibitors in the treatment of advanced NSCLC. The results of CROWN study where lorlatinib was given in the first line treatment were presented at ESMO 2020. In this randomized study, comparing lorlatinib with crizotinib, lorlatinib was superior in the term of PFS, HR was 0.28, p<0.001, this superiority was particularly pronounced in intracranial disease, where the percent of intracranial response was 82% in lorlatinib arm and only 23% in crizotinib arm, and percent of complete response per CT was 71% vs 7%. Lorlatinib has been recently approved for patients with advanced ALK-positive NSCLC, irrespectively of treatment line. Also of interest were two studies that inovatively used immunologic drugs as a combination in advanced NSCLC: in Check Mate 9LA randomized study, cytotoxic chemotherapy was given in paralell with nivolumab + ipilimumab for first two cycles, and compared with four cycles of chemoherapy. Median OS was significantly better: 15.6 vs 10.9 months, HR 0.66 and a overall response rate was 38% vs 25%. CITYSCAPE study give us inovative combination of two immuno-oncology drugs, tiragolumab as TIGIT inhibitor, and standard atezolizumab. Median PFS was particularly longer in the population of patients with high PD-L1 expression (NE vs 4.11 months, HR 0.30). In gastrointestinal oncology, last year will be remembered by introducing immunotherapy in first line treatment of metastatic colorectal cancer for patients with MSI-H tumors. In KN177, such patients were randomized to receive pembrolizumab or standard chemotherapy+/-biologic therapy, and after second interim analysis, there was a ery clear adventage for pembrolizumab in terms of mPFS (16.5 vs 8.2 months) and duraton of response (at 24 months, 83% vs 35%). The results are impressive, and it is for expected to be confirmed by OS adventage in future analyses. In urological oncology, JAVELIN Bladder 100 study demonstrated that the maintenance avelumab + best supportive care is superior over best supportive care alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma. In overall population, OS was 21.4 vs 14.3 months, HR 0.69, p<0.001, and the results are even better in PD-L1 positive population, with HR 0.56. These results are very probably practice changing, since cytotoxic chemotherapy have very modest achievements in the field of urothelial cancer.
ABSTRACT
Introduction: Upper tract urothelial carcinomas (UTUC) account for 5- 10% of urothelial malignancies. Rapid diagnosis is essential as 60% are invasive at diagnosis and confer poor prognoses. European Association of Urology (EAU) guidelines recommend CT urography (CTU) for initial diagnosis and staging of UTUCs. Diagnostic ureteroscopy (URS) is used second line where diagnosis is unclear. The COVID-19 pandemic has limited theatre access and may delay diagnosis of suspected UTUC. Our aim was to evaluate specific CTU findings in predicting UTUC to aid prompt diagnosis and risk stratification in a tertiary centre. Method: A retrospective analysis was performed on 122 patients who underwent CTU with diagnostic URS over two years from 2018-2019 for possible UTUC. Data including demographics, imaging and histology were collected from our electronic database. Results: 57 patients had confirmed UTUC, all had CT changes. CTU had an overall positive predictive value (PPV) of 45%. CT findings were divided into: hydronephrosis;filling defect/lesion;urothelial thickening;normal;or other. The PPV was highest for filling defects/lesions at 60%, hydronephrosis was 38%, urothelial thickening was 30%, and other was 33%. Of those with high-grade histology, 61% had evidence of filling defects/lesions and 24% had hydronephrosis. Conclusions: A specific CTU finding of filling defect/lesion in combination with cytology can aid diagnosis and risk stratification of UTUC. This may enable us to reduce use of diagnostic URS, as well as associated risks of intravesical seeding, necessary in the COVID-19 pandemic. With other CTU findings of hydronephrosis or urothelial thickening, a diagnostic URS may be required.