Neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy for muscle invasive bladder cancer (MIBC) has improves overall survival as compared to radical cystectomy (RC) alone. Our group has ...previously reported high risk features of MIBC that increase benefit of NAC. We report our institutional experience with NAC for patients with high-risk MIBC.
The records of consecutive high-risk, clinically node negative MIBC patients who underwent RC at our institution between 2005 and 2017 were reviewed. Pre-operative high-risk criteria included one or more of lymphovascular invasion, hydronephrosis, extravesical disease, and/or variant histology. Clinicopathologic and demographic information was collected, including eGFR and a previously validated frailty index. The primary outcomes were pathologic complete response (pCR=pT0N0M0) and downstaging to <pT2N0M0.
In our cohort (n=674), 74.3% (n=501) of patients received any NAC, most commonly dose dense MVAC (39.3%, n=265) followed by gemcitabine/cisplatin (GC) (13.1%, n=88), other cisplatin-based regimens (OCBR) (10.4%, n=70), and non-cisplatin regimen (NCBR) (11.6%, n=78) were used with similar frequency. The pCR rate was significantly lower without NAC at only 7.5% (n=13, p<0.01), while ddMVAC (30.2%, n=80), GC (25%, n=22), OCBR (25.7%, n=18), and NCBR (23.1%, n=18) all yielded similar results (p=0.55). When controlling for age, baseline eGFR, frailty index, and clinical T stage the chemotherapeutic regimen was not significantly predictive of achieving <ypT2N0M0 when ddMVAC was used as the reference group: GC (OR 0.75, p=0.28), other cisplatin-based regimens (OR 1.25, p=0.44), and non-cisplatin regimens (OR 0.80, p=0.4). At 5-years, cancer specific and overall survival were: 90% and 63% (MVAC); 85% and 47% (GC); 86% and 54% (OCBR); 81% and 50% (NCBR); 81% and 47% (none).
The benefits of NAC for MIBC have been repeatedly demonstrated, however, the rate of pathologic CR in high-risk muscle invasive disease has not been reported in a large series. In our high risk MIBC group, NAC led to significant higher pCR rate as compared to upfront surgery. These findings will serve as a benchmark for future neoadjuvant studies for evaluation of novel regimens.
The authors.
Has not received any funding.
M.T. Campbell: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Apricity health; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Janssen; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Merck. A.Y. Shah: Honoraria (self), Research grant / Funding (institution): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche Pharmaceuticals; Research grant / Funding (institution): BMS; Research grant / Funding (institution): EMD Serono. J. Gao: Travel / Accommodation / Expenses: AstraZeneca. A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. C.P.N. Dinney: Advisory / Consultancy: FKD Therapies Oy; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): NCI; Research grant / Funding (self): The University of Eastern Finland, Faculty of Health Sciences (UEFHS). A.M. Kamat: Advisory / Consultancy: Photocure; Advisory / Consultancy: FKD; Advisory / Consultancy: Abbott Molecular; Advisory / Consultancy: Theralase; Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: BioClin Therapeutics; Advisory / Consultancy: Cold Genesys; Advisory / Consultancy: Roviant; Advisory / Consultancy: Sessen Bio; Advisory / Consultancy: Asieris; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: US Biotest; Advisory / Consultancy: Ferring; Advisory / Consultancy: MDxHealth; Leadership role: IBCG; Advisory / Consultancy: TMC Innovation. N. Navai: Shareholder / Stockholder / Stock options: Allogene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pacira. All other authors have declared no conflicts of interest.
Prostate cancer shows a strong predilection to spread to the bones. Once prostate tumour cells are engrafted in the skeleton, curative therapy is no longer possible and palliative treatment becomes ...the only option. Herein, we review the multifactorial mechanisms and complex cellular interactions that take place inside the bone metastatic microenvironment. Emphasis is given to the detection and treatment of the micrometastatic stage of prostate cancer, as well as our recent attempts to target the bone metastasis microenvironment-related survival factors using an anti-survival factor manipulation which can increase the efficacy of anticancer therapies such as androgen ablation therapy and chemotherapy in advanced prostate cancer.
Normal (n = 20) and abnormal (n = 21) semen samples were explored for possible relationships between conventional semen parameters, chromatin status, and microdeletions in the Y chromosome. DNA ...fragmentation was detected by the terminal deoxynucleotidyl trasferase-mediated dUTP-nick end labelling (TUNEL) assay, chromatin condensation, and DNA packaging quality were assessed by chromomycin A3 (CMA3) staining. All men were investigated for Y chromosome microdeletions using polymerase chain reaction (PCR). No deletions were detected in 21 severely oligozoospermic men for the three screened regions (AZFa, AZFb, and AZFc). Men with normal semen parameters showed better chromatin condensation. Spermatozoa with low motility were more likely to contain loosely packaged chromatin. In the abnormal semen group, DNA fragmentation (TUNEL) correlated significantly with sperm motility, concentration, and chromatin packaging assessed by chromomycin A3. However sperm morphology did not correlate significantly with TUNEL and CMA3 staining.
Abstract To date, the effects of freezing on spermatogenesis have not yet been fully investigated at a molecular level. Antibody localization studies have identified the MutL homolog 1 (MLH1) ...protein, a mis-match repair protein, at the prophase I stage of meiosis, which allows the detection of recombination foci during pachytene. This study investigated the effect of long-term testicular tissue cryopreservation on meiotic prophase I, identified by recombination foci frequency and synaptonemal complex (SC) integrity. Frozen–thawed testicular tissues from 12 males who had each fathered a child were used. Because vasectomy or reverse vasectomy procedures are rare in the locale of the investigation, it was not possible to obtain fresh testicular tissue and use the males as their own controls. Immunocytogenetic analysis of 612 spermatocytes at the pachytene stage was performed. The results indicated a mean number of MLH1 foci of 49.2 (SD ± 5.9), and no correlation was found between the freezing period, the MLH1 frequency and the SC integrity. The results suggest that freezing of testicular tissue taken post-puberty does not appear to be detrimental to the crossover process as identified by occurrence of MLH1 loci.
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