Displaying publications 21 - 32 of 32 in total

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  1. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kübler H, et al.
    Urol Oncol, 2018 02;36(2):43-53.
    PMID: 29102254 DOI: 10.1016/j.urolonc.2017.10.002
    OBJECTIVE: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

    PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.

    RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.

    CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

  2. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Kübler H, Stenzl A, et al.
    Urol Oncol, 2018 02;36(2):54-59.
    PMID: 29196179 DOI: 10.1016/j.urolonc.2017.11.007
    PURPOSE: Currently, identified factors for urethral recurrence (UR) are based on individual reporting which has displayed controversy. In addition, risk of UR is one of the limiting factors to offer neobladder diversion during radical cystectomy (RC). We aim to systematically evaluate the incidence and risk factors of UR post-RC and its effect on survival.

    MATERIALS AND METHODS: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies.

    RESULTS: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies.

    CONCLUSION: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.

  3. Fahmy O, Khairul-Asri MG, Hadi SHSM, Gakis G, Stenzl A
    Urol Int, 2017;99(3):249-256.
    PMID: 28675891 DOI: 10.1159/000478789
    BACKGROUND: The role of radical prostatectomy (RP) is still controversial for locally advanced prostate cancer (PC). Radiotherapy (RT) and hormonal therapy (HT) are usually used as a primary treatment.

    MATERIAL AND METHODS: A systematic online search was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Eligible publications reporting the overall survival (OS) and/or disease-specific survival (DSS) were included. A total of 14 studies, including 17,869 patients, were considered for analysis. The impact of therapeutic modalities on survival was assessed, with a risk of bias assessment according to the Newcastle Ottawa Scale.

    RESULTS: For RP, RT, and HT, the mean 10-year OS was 70.7% (95% CI 61.3-80.2), 65.8% (95% CI 48.1-83.3), and 22.6% (95% CI 4.9-40.3; p = 0.001), respectively. The corresponding 10-year DSS was 84.1% (95% CI 75.1-93.2), 89.4% (95% CI 70.1-108.6), and 50.4% (95% CI 31.2-69.6; p = 0.0127), respectively. Among all treatment combinations, RP displayed significant improvement in OS when included in the treatment (Z = 4.01; p < 0.001). Adjuvant RT significantly improved DSS (Z = 2.7; p = 0.007). Combination of RT and HT favored better OS in comparison to monotherapy with RT or HT (Z = 3.61; p < 0.001).

    CONCLUSION: Improved outcomes in advanced PC were detected for RP plus adjuvant RT vs. RP alone and RT plus adjuvant HT vs. RT alone with comparable survival results between both regimens. RP with adjuvant RT may present the modality of choice when HT is contraindicated.

  4. Patel V, Collazo Lorduy A, Stern A, Fahmy O, Pinotti R, Galsky MD, et al.
    Bladder cancer (Amsterdam, Netherlands), 2017 Apr 27;3(2):121-132.
    PMID: 28516157 DOI: 10.3233/BLC-170108
    Background: Cisplatin-based combination chemotherapy is standard treatment for metastatic urothelial carcinoma; however, the vast majority of patients experience disease progression. As systemic therapy alone is rarely curative for the treatment of metastatic urothelial cancer, not only are new therapies needed but also refinement of general treatment principles. Herein, we conducted a systematic review and meta-analysis to explore the role of metastasectomy in metastatic urothelial carcinoma. Methods: We conducted a systematic review of the literature regarding local treatment for metastatic urothelial carcinoma. An online electronic search of the PubMed/MEDLINE and EMBASE databases was performed to identify peer-reviewed articles. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information was then extracted including number of patients, gender, the site of the primary urothelial tumor, site of metastasis, chemotherapy before or after metastasectomy, overall survival (OS), and disease specific survival (DSS) after metastasectomy. A meta-analysis was performed with those studies with sufficient survival data to obtain pooled overall survival. The article quality was assessed using the Cochrane Handbook "risk of bias" tool. Results: Seventeen out of 3963 articles were eligible for review between 1990-2015, including a total of 412 patients. The mean time to recurrence after metastasectomy was 14.25 months. The overall survival from time of metastasectomy ranged from 2 to 60 months. Pooled analyses of studies reported survival data revealed an improved overall survival for patients treated with metastasectomy compared with non-surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49-0.81). All, except for three studies, were retrospective and non-randomized, leading to a high risk of bias associated with patient selection, patient attrition, and reporting. Such high potential of selection bias may lead to higher OS than expected. Additionally, treatment and outcome details reported across studies was highly variable. Conclusions: Limited conclusions can be drawn from the available literature exploring the role of metastasectomy in the management of metastatic urothelial cancer due to lack of uniform reporting elements and multiple sources of bias particularly related to a lack of prospective randomized trials. As a subset of patients treated with metastasectomy achieve durable disease control, this approach may be considered for select patients.
  5. Shsm H, Fahmy UA, Alhakamy NA, Khairul-Asri MG, Fahmy O
    J Pers Med, 2021 Nov 13;11(11).
    PMID: 34834547 DOI: 10.3390/jpm11111195
    BACKGROUND: Neoadjuvant chemotherapy is the standard of care before radical cystectomy for muscle invasive bladder cancer. Recently, checkpoint inhibitors have been investigated as a neoadjuvant treatment after the reported efficacy of checkpoint inhibitors in metastatic urothelial carcinoma.

    OBJECTIVES: The aim of this systematic review is to investigate the role of checkpoint inhibitors as a neoadjuvant treatment for muscle invasive bladder cancer before radical cystectomy.

    METHODS: Based on the PRISMA statement, a systematic review of the literature was conducted through online databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Suitable publications were subjected to full-text assessment. The primary outcome of this review was to identify the impact of neoadjuvant immunotherapy on the oncological outcomes and survival benefits.

    RESULTS: From the retrieved 254 results, 8 studies including 404 patients were included. Complete response varied between 30% and 50%. Downstaging varied between 50% and 74%. ≥Grade 3 AEs were recorded in 8.6% of patients who received monotherapy with either Atezolizumab or Pembrolizumab. In patients who received combination treatment, the incidence of ≥Grade 3 AEs was 16.3% for chemoimmunotherapy and 36.5% for combined immunotherapy. A total of 373 patients (92%) underwent radical cystectomy. ≥Grade 3 Clavien-Dindo surgical complications were reported in 21.7% of the patients. One-year overall survival (OS) and relapse-free survival (RFS) varied between 81% and 92%, and 70% and 88%, respectively.

    CONCLUSION: The evidence on the use of immune checkpoint inhibitors in the setting of pre-radical cystectomy is quite limited, with noted variability within published trials. Combination with chemotherapy or another checkpoint inhibitor may boost response, although prospective studies with extended follow-up are needed to report on the survival advantages.

  6. Fahmy O, Alhakamy NA, Khairul-Asri MG, Ahmed OAA, Fahmy UA, Fresta CG, et al.
    J Pers Med, 2021 Dec 23;12(1).
    PMID: 35055323 DOI: 10.3390/jpm12010008
    Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated.

    OBJECTIVES: The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors.

    METHODS: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle-Ottawa Scale for the randomized and non-randomized trials, respectively.

    RESULTS: From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; p = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; p < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; p = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; p = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; p = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; p = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; p = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; p = 0.003).

    CONCLUSIONS: Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.

  7. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Stenzl A, Gakis G
    J Urol, 2017 02;197(2):385-390.
    PMID: 27569436 DOI: 10.1016/j.juro.2016.08.088
    PURPOSE: There is controversy in the literature about the oncologic significance of incidental prostate cancer detected at radical cystoprostatectomy for bladder cancer.

    MATERIALS AND METHODS: An online search was done for studies reporting incidental prostate cancer in cystoprostatectomy specimens. After following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines we identified a total of 34 reports containing 13,140 patients who underwent radical cystoprostatectomy for bladder cancer with no previous history of prostate cancer. A cumulative analysis was performed on the available data regarding prevalence, clinicopathological features and oncologic outcomes. RevMan, version 5.3 was used for data meta-analysis.

    RESULTS: Of the 13,140 patients incidental prostate cancer was detected in 3,335 (24.4%). Incidental prostate cancer was significantly associated with greater age (Z = 3.81, p = 0.0001, d = 0.27, 95% CI -0.14-0.68), lymphovascular invasion of bladder cancer (Z = 2.07, p = 0.04, r = 0.14, 95% CI 0.09-0.18) and lower 5-year overall survival (Z = 2.2, p = 0.03). Among patients with clinically significant and insignificant prostate cancer those with clinically significant prostate cancer significantly more frequently showed a positive finding on digital rectal examination (Z = 3.12, p = 0.002, r = 0.10, 95% CI 0-0.19) and lower 5-year overall survival (Z = 2.49, p = 0.01) whereas no effect of age was observed (p = 0.15). Of 1,320 patients monitored for biochemical recurrence prostate specific antigen recurrence, defined as prostate specific antigen greater than 0.02 ng/ml, developed in 25 (1.9%) at between 3 and 102 months.

    CONCLUSIONS: This meta-analysis suggests that incidental prostate cancer detected during histopathological examination of radical cystoprostatectomy specimens might be linked with adverse characteristics and outcomes in patients with invasive bladder cancer.

  8. Schubert T, Renninger M, Schmid MA, Hassan FN, Sokolakis I, Fahmy O, et al.
    Urol Oncol, 2020 01;38(1):4.e7-4.e15.
    PMID: 31537484 DOI: 10.1016/j.urolonc.2019.08.013
    OBJECTIVES: To assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC).

    MATERIAL AND METHODS: A total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan-Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10-55).

    RESULTS: Of the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence.

    CONCLUSIONS: In this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.

  9. Aizat Sabri I, Yusof MR, Jagwani AV, Fahmy O, Lee CK, Mg-Khairul Asri MA, et al.
    Urologiia, 2022 Dec.
    PMID: 36625624
    We present a rare case of leiomyoma of the urinary bladder that was diagnosed during pregnancy. The case of a 29-year-old woman primigravida at 13 weeks of pregnancy who presented with 6 months history of abdominal swelling which was gradually increasing in size. Computed tomography done revealed a large heterogenous mass(enhancing) with an area of non-enhancing (necrosis) suggestive of malignant ovarian tumor. The histological findings of the surgical specimen confirmed a leiomyoma of the urinary bladder. The clinical presentation, imaging findings, and management of this relatively rare benign tumor are discussed in this case report.
  10. Khor V, Sidhu S, Muhammad Afiq MFO, Pushpanathan M, Fahmy O, Khairul Asri MG, et al.
    Singapore Med J, 2024 Mar 01;65(Suppl 1):S35-S40.
    PMID: 35139632 DOI: 10.11622/smedj.2022008
  11. Fahmy O, Alhakamy NA, Rizg WY, Bagalagel A, Alamoudi AJ, Aldawsari HM, et al.
    J Clin Med, 2021 Oct 31;10(21).
    PMID: 34768647 DOI: 10.3390/jcm10215127
    Prostate cancer (PCa) represents the most commonly non-cutaneous diagnosed cancer in men worldwide and occupies a very wide area of preclinical and clinical research. Targeted therapy for any cancer depends on the understanding of the molecular bases and natural behaviour of the diseases. Despite the well-known effect of androgen deprivation on PCa, many patients develop resistance either for antiandrogen therapy or other new treatment modalities such as checkpoint inhibitors and chemotherapy. Comprehensive understanding of the development of PCa as well as of the mechanisms underlying its progression is mandatory to maximise the benefit of the current approved medications or to guide the future research for targeted therapy of PCa. The aim of this review was to provide updates on the most recent mechanisms regarding the development and the progression of PCa. According to the current understanding, future treatment strategies should include more predictive genetic and biomarker analysis to assign different patients to the expected most appropriate and effective treatment.
  12. Alfaleh MA, Fahmy O, Al-Rabia MW, Abourehab MAS, Ahmed OAA, Fahmy UA, et al.
    Sci Rep, 2022 Nov 14;12(1):19446.
    PMID: 36376469 DOI: 10.1038/s41598-022-24151-3
    As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.
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