Infections Articles

Articles

  • Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients.

    Consumption of cruciferous vegetables is associated with a decreased risk of developing prostate cancer. Antineoplastic effects of cruciferous vegetables are attributable to bioactive indoles, most prominently, 3, 3'-diindolylmethane (DIM).

    Published April 22, 2016
  • Associated measures to antibiotic prophylaxis in urology.

    Urinary tract infections are amongst the most frequent nosocomial infections followed by surgical site infections (SSI). Antibiotic prophylaxis is only one way to reduce the risk of post-operative infection.

    Published June 30, 2019
  • Beyond the Abstract - Prevalence and risk factors for quinolone resistance among Escherichia coli strains isolated from males with community febrile urinary tract infection, by Alex Smithson, PhD

    BERKELEY, CA (UroToday.com) - E. coli is responsible for the vast majority of febrile urinary tract infections (FUTI) in men.

    Published October 11, 2011
  • Beyond the Abstract - The changing pattern of antimicrobial resistance within 42033 Escherichia coli isolates from nosocomial, community and urology patient-specific urinary tract infections, Dublin, 1999-2009, by Ivor Cullen

    BERKELEY, CA (UroToday.com) - E.coli infection is the most causative pathogen in urinary tract infections, accounting for 70-80% in the community and 50-60% in the hospital setting.

    Published January 19, 2012
  • Beyond the Abstract - Urinary tract infection before and after mid-urethral slings: Culture-proven diagnosis and analysis of risk factors, by Ahmed S. El-Hefnawy, MD

    BERKELEY, CA (UroToday.com) - Although postoperative complications of midurethral slings are well acknowledged, urinary tract infection is less commonly addressed than other complications and its prevalence is not well defined in literature.

    Published November 2, 2011
  • Beyond the Abstract - Uropathogenic Escherichia coli induces chronic pelvic pain, by Praveen Thumbikat, PhD, et al.

    BERKELEY, CA (UroToday.com) - Prostatitis is a common urologic disease that results in over 2 million outpatient visits per year in the United States, including 8% of all visits to urologists and 1% of those to primary care physicians.

    Published October 21, 2011
  • Cabazitaxel Demonstrates Improved Overall Survival when Compared to an Alternative AR-targeted Agent (CARD) - Cora Sternberg

    Cora Sternberg, MD, FACP, shares her experiences from the CARD study, which was the first trial to evaluate the sequencing of the androgen-signaling–targeted inhibitor (abiraterone or enzalutamide) compared to cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) who had been previously treated with docetaxel and the alternative androgen-signaling–targeted agent (abiraterone or enzalutamide). In this conversation with Alicia Morgans, MD, MPH, Dr. Sternberg describes the overall survival data where cabazitaxel was consistently superior to a second pathway inhibitor.  Cabazitaxel was also shown to double radiologic progression-free survival with a similar hazard ratio for patients both above and below 70 years. Dr. Sternberg outlines the clinical relevance of these data in the geriatric population. 

    Biographies:

    Cora Sternberg MD, FACP Professor Medicine and Clinical Director of the Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York.

    Alicia Morgans, MD, MPHAssociate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.


    Read the Full Video Transcript

    Alicia Morgans: Hi, this is Alicia Morgans, GU medical oncologist and Associate Professor of Medicine at Northwestern University in Chicago, Illinois. I'm so excited to have here with me today, a colleague and friend, a Full Professor of Medicine at Weill Cornell Medicine, as well as a GU medical oncologist, Dr. Cora Sternberg, who is also the Clinical Director of the Englander Institute for Precision Medicine, as well as being one of the Primary Investigators on the CARD trial. She's talked to us about it several times before. We always appreciate hearing her insights. Thank you so much for being here with us today, Dr. Sternberg.

    Cora Sternberg: Thank you very much. It's always a pleasure to be here with you and with UroToday. The CARD study was the first study to look at the sequencing of novel therapies for patients with metastatic CRPC. And what we did was we took patients with metastatic CRPC, metastatic castration-resistant prostate cancer, who had all received docetaxel and had received one novel AR targeting agent, which was either abiraterone or enzalutamide and who had failed that AR targeting agent within 12 months of receiving the agent. They were then randomized on a one-to-one basis to receive either cabazitaxel 25 milligrams per meter squared, plus GCSF and prednisone, or to receive the alternative AR targeted agents, either abiraterone and prednisone or enzalutamide, depending what they had received before. Now, the dose of cabazitaxel at the time that this study was done in Europe is the dose of 25 milligrams per meter squared, but GCSF was given and subsequently known that perhaps the dose of 20 milligrams per meter squared gives very similar results.

    At any rate, the primary endpoint was radiologic progression-free survival and secondary endpoints included overall survival. And what was reported already in the New England Journal of Medicine was the primary endpoint of radiologic progression-free survival with a hazard ratio of 0.54. We can say that cabazitaxel as compared to abiraterone or enzalutamide doubled the radiologic progression-free survival. Doubled it. And in terms of overall survival, the hazard ratio was 0.64, which corresponded to a decrease in death of 36%.

    And these data have not been updated recently. Those were the data published in the New England Journal of Medicine. This study was run between 2015 and 2018. Run primarily in Europe. And really showing the cabazitaxel chemotherapy was better, more efficacious than an AR targeted agent if patients had already failed another AR targeted agent. And it was a selected population because the patients actually had not done very well on an AR targeted agent. They'd responded for less than 12 months.

    What was done in the two abstracts presented at ASCO, the first one was a deeper dive, let's say, into the univariate and multivariate analysis of overall survival. And looking first at a univariate analysis, they looked at many of the things that had prognostic value in the past in patients with metastatic CRPC such as PSA, alkaline phosphatase, LDH, age, visceral disease,  many things. And all of these did have prognostic value in univariate analysis, but when looked at in multivariate analysis, the most important items for overall survival were a high NLR, nuclear lymphocyte ratio, a decreased hemoglobin, or an increase in PSA. These all portended a worse overall survival in the multivariate analysis model.

    And in all of the factors, both univariate and multivariate that were looked at, cabazitaxel was superior to adding a second pathway inhibitor in all. The overall survival for the various endpoints we'e looked at and no matter what was looked at, also in terms of when we started treatment, if overall survival was the time for metastatic disease and metastatic CRPC diagnosis or overall survival from metastatic CRPC diagnosis or overall survival from the first life-extending treatment or overall survival from the second life-extending treatment, all of these factors all showed an improvement with cabazitaxel as compared to the alternative AR inhibitor.

    And this is I think, a very important thing to know in terms of sequencing, because many people like to use one AR inhibitor after the other, thinking that perhaps they're less toxic or whatever they're doing. And I think that probably we've shown that it's less efficacious to do that, particularly in patients who didn't respond for more than 12 months. And the results support the use of cabazitaxel over abiraterone or enzalutamide as a standard of care in patients previously treated with both docetaxel and the alternative AR targeted agent.

    Now, the other abstract looked at age and we know according to the SIOG, the Society of Geriatric Medicine guidelines, we should look at a senior adult population as those over 70 as compared to those less than 70. And that's why we chose that cutoff. I don't know how relevant that still is, but the truth is that in CARD, the median age for patients on cabazitaxel was 70 years of age. And there was quite more than a third of the population was more than 75 years of age, actually.

    We looked at the cutoff between greater than 70 and less than 70. And here we found that cabazitaxel doubled the radiologic progression-free survival with a hazard ratio of 0.58 in patients that were 70 years or older and 0.47 in those less than 70 years. What we see again, a recapitulation, the fact is that about 50% of the patients in CARD were older than 70 and that the hazard ratio really was pretty much the same in terms of radiologic progression-free survival and overall survival, irrespective of age.

    And regarding the safety, which is really important when people are worried about age, I think that if you look at it, what we showed was that the grade more than 3 adverse events in patients greater than 70 versus less than 70, we saw that there was a slightly higher frequency in those older than 70. Grade 3 ischemia, diarrhea and febrile neutropenia occurred more frequently in patients more than 70 of age who received, cabazitaxel and grade more than 3 cardiac events, infection, kidney adverse events more frequently in those greater than 70 receiving abiraterone or enzalutamide. So in many of our patients with comorbidities such as cardiovascular disease, it may not be so gentle to give abiraterone or enzalutamide. It may be a better option to give chemotherapy with cabazitaxel and GCSF as was done in this particular trial. I think this trial supported the use of cabazitaxel over abiraterone or enzalutamide as a standard of care, irrespective of age in patients previously treated with docetaxel and the alternative androgen receptor-targeted agent.

    Now, I would like to say that these results were a third-line study. The patients were highly selected. The patients received an androgen receptor-targeted agent and they didn't respond for more than 12 months. But honestly, if I look deeper into the data and I don't even know if this is published, the patients who received in the hormone-sensitive prostate cancer setting, were 40% and the patients who received an alternative abiraterone or enzalutamide in the castration-resistant setting after docetaxel were 60%. This is because these drugs were not approved as early as they were in the United States in Europe. And the study was primarily conducted in Europe.

    If you compare these results to the TheraP trial that was presented at ASCO by Hofman et al. from Australia was a very interesting trial that compared to lutetium PSMA treatment to cabazitaxel. They showed looking at the PSA 50 that lutetium PSMA-50 was perhaps better than cabazitaxel. The response rate in terms of PSA was very similar 37 and 38%. But if you look at this closely, the PSMA-50 is really not a surrogate, as far as we know for overall survival. And the other thing is that the patients on that trial were highly selected patients who had a PSMA positive scan and another PET scan that showed active disease. And they also had a PSA of over 20. There's a different kind of selection here. And some 30% of patients were not admitted into that trial who did not fit those strict criteria of expressing PSMA.

    Now we know well that PSMA and PSA may not be the best way to look at these patients, and in the CARD trial that we selected patients for not responding to the alternative therapy, we didn't select patients based on having a high PSA. And not selecting patients on a high PSA means we treated all-comers that were not treated on the other trial. In terms of sequencing, I think there's still a lot of work to be done in terms of cabazitaxel and PSMA. And I think that their study is an excellent study, but we need further follow-up. We probably need to do other sequencing studies in the future, both to understand and put it in perspective, both CARD and the PSMA TheraP trial.

    Alicia Morgans: Thank you so much for putting that all in perspective. And I did fail to mention, but wanted to make sure it was clear, you were actually on the Steering Committee of the CARD trial and we so appreciate hearing your insights both in terms of the deeper dive on the overall survival, but also certainly in the geriatric analysis and in the context of the TheraP trial. I think we so appreciate this, especially because you have such an interest in real-world applications for the data. And as you said, particularly things like the geriatric analysis are quite reassuring when we're thinking about using a treatment in this third-line setting and many people feel that perhaps this is too toxic of a drug.

    What your study really brought out, and I just want to emphasize this for the listeners is that, although there are some side effects that may be more common in this geriatric or over 70 population, there are certainly some side effects that are more common when using another AR targeted agent. And of course, if that agent is also not controlling the prostate cancer but causing these comorbidities in terms of cardiac events, for example, that's really not doing patient any service by any stretch. Can you let me know, how do you use the data that you just talked about, the data, particularly the geriatric data, in your day to day clinical practice?

    Cora Sternberg: Well, I think that that data is really important. I think that what we have shown and we know this from other studies, these splice variants, et cetera, that patients who have had an AR targeting agent and not done well on it, particularly if that was the last treatment that they just received, they are not the patients who will do very well in another AR targeted agent. And we may think that when we have an elderly patient that we're doing them a huge favor by giving them another AR targeted agent, but perhaps it would be better and more gentler to give them chemotherapy with cabazitaxel. In this case, it was done with 25 per meter squared and GCSF, but we know from the PROSELICA study that you can give 20 per meter squared.

    And in my own practice, if I have a really elderly patient, I will give 20 per meter squared and GCSF and try to be as gentle as possible in elderly patients. And I think that if you control their disease, we've seen quality of life data from the last GU ASCO, that controlling their disease as you've said, is the most important thing that we can do. And we think we're being gentle by giving them a pill instead of chemotherapy, but perhaps that's not the most gentle way of going about it.

    Alicia Morgans: I completely agree. Well, as we wrap up this tour de force through the recently reported CARD data, the TheraP data, all of this data really reflecting our understanding of cabazitaxel as it is still quite a relevant and useful tool in our armamentarium against prostate cancer, what would your closing thought be, or your message to the audience?

    Cora Sternberg: Well, I think that cabazitaxel is really a very good drug after failing docetaxel. We know this from several studies. Cabazitaxel will become generic in Europe very shortly in the next year and I'm not sure when it will be in the United States and we're still waiting for PSMA scanning to be FDA approved in the United States and lutetium to be approved as a therapy. I think it's a very promising, interesting therapy and there probably will be a place for all of these agents, both cabazitaxel and lutetium therapy. But I think we need to understand the right sequence of these treatments. When is the best time to give which one? I think both of these trials are looking in third-line treatment. And I think that it's always very difficult to compare among trials when they use completely different selection criteria.

    And I think that that's important and one should use what they're familiar with and feel most comfortable with what they think will be best for their patients. But again, the cost will be a problem as well and we need to consider cost efficacy. Cabazitaxel works against AR dependent and AR independent cells and we know that when many people are in the third -ine, that many of the cells are AR independent. That's an advantage of using chemotherapy as opposed to an AR targeted therapy, such as lutetium PSMA. I think we need to have more data from the TheraP trial. We need to do probably more sequencing in the future to understand better the place of PSMA lutetium, eventually actinium, and also chemotherapy.

    Alicia Morgans: Well, I could not agree more and I appreciate your continued efforts to help us as a field, understand how to best use all of these options in a way that makes sense in selecting the treatment for an individual patient that will hopefully work and will be safe and will be the right choice. Thank you so much for your time and your expertise today, Dr. Sternberg.

    Cora Sternberg: My pleasure.

    Published June 21, 2020
  • Cancer diagnostic rates during the 2020 'lockdown', due to COVID-19 pandemic, compared with the 2018-2019: an audit study from cellular pathology.

    We performed an audit to evaluate the impact of the COVID-19 pandemic-related delay in the diagnosis of major cancers at a Pathology Unit of a Secondary Care Hospital Network in Italy.

    A comparison was made among the number of first cellular pathological diagnoses of malignancy made from the 11th to the 20th week of the years 2018-2020.

    Published July 1, 2020
  • Hospitalization before surgery and subsequent risk of infective complications after radical cystectomy: A population-based analysis.

    The length of stay prior to surgery increases the risk of postoperative infections (PIs) in several surgical settings, such as cardiac, orthopedic, and general surgery. However, data for urological oncology procedures are limited.

    Published August 10, 2017
  • Increased infection risk in Addison's disease and congenital adrenal hyperplasia: a primary care database cohort study.

    Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown.

    Published September 29, 2019
  • Infected penile prosthesis: literature review highlighting the status quo of prevention and management.

    Erectile dysfunction affects over 50% of men 70 years and above, and penile prosthesis (PP) is its third-line treatment. Complications of PPs include infection, however, no formal guidelines exist for its management.

    Published December 2, 2018
  • Percutaneous nephrolithotomy: complications and how to deal with them.

    Percutaneous nephrolithotomy is a common surgical treatment for large and complex stones within the intrarenal collecting system. A wide variety of complications can result from this procedure, including bleeding, injury to surrounding structures, infection, positioning-related injuries, thromboembolic disease, and even death.

    Published November 20, 2017
  • Risk Factors and Microbial Distribution of Urinary Tract Infections Following Radical Cystectomy.

    OBJECTIVE - To evaluate clinicopathologic features associated with the risk of urinary tract infection (UTI) after radical cystectomy (RC), and determine the underlying organisms responsible for these events.

    METHODS - We reviewed 1,248 patients treated with RC for bladder cancer from 2000-2010 at Mayo Clinic.

    Published May 3, 2016
  • Staghorn renal stones: what the urologist needs to know.

    Patients with staghorn renal stones are challenging cases, requiring careful preoperative evaluation and close follow-up to avoid stone recurrence. In this article we aim to discuss the main topics related to staghorn renal stones with focus on surgical approach.

    Published March 29, 2020
  • The Urinary Microbiome: Implications in Bladder Cancer Pathogenesis and Therapeutics.

    Recent investigation has proven that the bladder is not sterile. However, the implications of this finding in the pathophysiology and management of urothelial cell carcinoma have not been fully described.

    Published January 11, 2019