Functional And Clinical Significance Of Specific Mutations In This Case
As the special genetic pattern of NEPC reflects its cellular origin, the genetic alterations in two samples collected at different stages were investigated using whole-exome sequencing. The first was a mixed adenocarcinoma and neuroendocrine cancer sample at CRPC, whereas the second was a pure SCC/NEPC at the last stage. We described the mutational landscape and applied phylogenetic reconstruction to analyze the dynamic clonal progression. We estimated and clustered the cancer cell fraction to track and visualize the clonal evolution of each tumor using PyClone .
Figure 3 The altered landscape and phylogenetic reconstruction of the two samples. The second panel shows the cancer cell fraction estimated by using PyClone and calculated using the read depth of mutations, copy numbers, and purity of tumors. Other panels are showing the frequency of mutations in three types of prostate cancer using public data from the cBioPortal . Important functional cancer genes are marked in red. Overview of copy number alterations and cancer genes encompassed in segments are shown in red. Fishplot indicating the dynamic clonal progression of the tumor, and clonal evolution tree showing the phylogenetic relationship between the two samples.
Retrieval Method Of The Related Literature
All literature reports relating to SmCC of the prostate were accessed from the China Hospital Knowledge Database , the Chinese Medical Journal Database , the Chinese Medical Citation Index , and the Wanfang Database using the keywords small cell carcinoma, prostate, and neuroendocrine. The search located 29 cases in 19 reports -. The contents of these reports were then reviewed. Two cases were found to be duplicated and were eliminated -. Another case was also eliminated due to incomplete clinical and pathological data . In total, 26 cases were eligible -. Data on age, clinical symptoms and signs, serum PSA levels, DRE findings, ultrasound scans and MRI, surgical approach, postoperative therapy, follow-up time, and survival were collected.
Where Can I Get Support
Being diagnosed with any kind of prostate cancer can be frightening and overwhelming. If you are told you have a rare prostate cancer you may worry about what this means and feel frustrated that there isnt much information available about your diagnosis and treatment.
No matter what youre feeling or thinking, there is support available if you want it. You can speak to our Specialist Nurses, in confidence or chat with them online. Our Dealing with prostate cancer page looks at things you can do to help yourself and people who can help.
Visit our wellbeing hub for information to help support you in looking after your emotional, mental, and physical wellbeing. If you are close to someone with prostate cancer, find out more about how you can support someone with prostate cancer and where to get more information.
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Prostate Cancer With A Normal Psa: Small Cell Carcinoma Of The Prostate A Rare Entity
Pure small cell carcinoma of the prostate is extremely rare. When it does occur, it is usually in concordance with prostatic adenocarcinoma. Early diagnosis is difficult as the carcinoma tends to spread early to visceral organs without concordant elevation of prostate-specific antigen . Because this condition is rare, no standard treatment regimen has been established, and the overall prognosis remains poor.
This case report describes clinical characteristics of a 67-year-old man with pure small cell carcinoma of the prostate. The unique clinical and biological features of this histologic type of prostate cancer are discussed.
Deadly Form Of Advanced Prostate Cancer Is Common Calls For Distinct Treatment
- Date:
- University of California San Francisco
- Summary:
- A new study of prostate cancer in 202 men, whose cancers had spread and were resistant to standard treatment, found that a surprisingly large number of these cancers about 17 percent belong to a deadlier subtype of metastatic prostate cancer.
A new study of prostate cancer in 202 men, whose cancers had spread and were resistant to standard treatment, found that a surprisingly large number of these cancers about 17 percent belong to a deadlier subtype of metastatic prostate cancer.
Previously, it was thought that these cancers constituted less than 1 percent of all prostate cancers.
The study, which was led by researchers at UC San Francisco and published online July 9 in the Journal of Clinical Oncology, suggests that this prostate cancer subtype, called treatment-emergent small cell neuroendocrine prostate cancer , might in the future be routinely and more successfully treated with targeted drugs that already are being developed or tested in clinical trials.
The research team identified specific genetic mutations and patterns of gene expression that are found in t-SCNC, but are distinct from the more common type of prostate cancer known as adenocarcinoma. Among the patterns identified in t-SCNC was higher activity of specific transcription factor proteins proteins that switch on production of other proteins that drive cancer growth.
Story Source:
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Research And Clinical Trials
Doctors are always trying to improve the diagnosis and treatment of cancer. But small cell prostate cancer is very rare, so it is harder to research than other more common types of prostate cancer.
Researchers are looking into immunotherapy for small cell prostate cancer. This is early stage research and its not clear whether these treatments will work well for small cell prostate cancer.
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Case Report: Systemic Treatment And Serial Genomic Sequencing Of Metastatic Prostate Adenocarcinoma Progressing To Small Cell Carcinoma
- 1Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
- 2Department of Oncology, Shidong Hospital, Affiliated to University of Shanghai for Science and Technology, Shanghai, China
- 3Department of Bioinformatics, Center for Translational Medicine, Second Military Medical University, Shanghai, China
- 4Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- 5Department of Urology, The 903th PLA Hospital, Hangzhou, China
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Diagnosing Rare Prostate Cancers
Rarer prostate cancers can be harder to diagnose. For example, some dont cause your prostate specific antigen level to rise. This means theyre not always picked up by a PSA test. Because of this, some rare cancers may not be diagnosed until they have already spread outside the prostate. Read more about the PSA test and other tests used to diagnose prostate cancer.
Some rare prostate cancers may only be picked up after having a biopsy to check for prostate cancer, or surgery called transurethral resection of the prostate to treat an enlarged prostate. The tissue removed during the biopsy or TURP is looked under a microscope to see if you have common prostate cancer or a rare type of prostate cancer. Rare cancers arent always given a Gleason score after a biopsy. This is because they can behave differently to common prostate cancer and cant be measured in the same way.
Because rare cancer can be aggressive and spread outside the prostate, you will probably have more tests to see if they have spread. These include:
Working To Treat A Deadly Form Of Prostate Cancer
July 11, 2018
A deadly form of advanced prostate cancer is more common than experts previously thought.
A new study looked at about 200 men with prostate cancer that had spread and were resistant to standard treatment. It found that about 17 percent of the men had developed a deadlier subtype of prostate cancer called treatment-emergent small cell neuroendocrine prostate cancer.
Clinical recognition of the emergence of small cell carcinoma during the usual progression of prostate cancer is increasing, said Moffitt pathologist Dr. Jasreman Dhillon. The increase is largely attributed to the use of more effective androgen deprivation therapies in recent years. This type of prostate cancer progresses rapidly and combinational chemotherapy is the only treatment option at this time.
The studys findings suggest the deadly cancer subtype could also be successfully treated with targeted therapy, a type of treatment that is tailored to individual tumors.
Moffitt is already using a type of individualized treatment called adaptive therapy. It utilizes mathematical models to analyze a patients response to treatment to create a unique and constantly evolving treatment strategy.
Dr. Jingsong Zhang, a medical oncologist in Moffitts Genitourinary Oncology Program, is currently conducting a clinical trial of adaptive therapy for prostate cancer patients.
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Open Access License / Drug Dosage / Disclaimer
This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License . Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor. The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Potential Strategies To Target The Pathway And Implications For Clinical Practice
Notably, this case study has some limitations. While longitudinal sampling combined with bulk sequencing could distinguish tumor subclones and monitor tumor progression, for the special tumor type observed in this casewith higher heterogeneity and more complex cellular componentssingle-cell sequencing may be a better and more accurate solution . Alternatively, in a previous report, transcription factors have been utilized for the molecular subtyping of small cell lung cancer however, this has not been applied in clinical practice . Accordingly, further research is required to explore the value of transcription factor typing to guide clinical treatment.
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Recalcitrant Cancer Research Act
In 2013, the US Congress passed the Recalcitrant Cancer Research Act, which mandated increased attention to certain recalcitrant cancers, including small cell lung cancer. That led to the National Cancer Institute supporting small cellspecific research through a consortium.
As a result, new experimental drugs for small cell lung cancer are currently being tested, including Iadademstat and Keytruda .
Relationship Between Target And Therapy
For those patients with pure small cell carcinoma, SCLC regimens such as carboplatin-etoposide with or without the anti-PDL1 immune checkpoint inhibitor atezolizumab ) may also be considered. Docetaxel with carboplatin is also a reasonable option for patients who have not previously received docetaxel, given the frequent mixed CRPC/NEPC features. A major clinical challenge is in what to do next after platinum-based chemotherapy. There are limited data in the second line and beyond settings. For mixed tumors with both adenocarcinoma and NEPC elements, the choice of therapy depends on the dominant histology and clinical context. Next line SCLC regimens may be considered for those with small cell NEPC these include lurbinectedin, topotecan, pembrolizumab, ipilimumab/nivolumab. Given limited data, we would encourage participation in clinical trials. Further, ADT should be considered in both de novo and treatment-related NEPC cases given tumor heterogeneity.
Citation: Endocrine-Related Cancer 28, 8 10.1530/ERC-21-0140
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Current Trend Of Worsening Prognosis Of Prostate Small Cell Carcinoma: A Population
To determine the accurate age-adjusted incidence of prostate small cell carcinoma , update the clinical and pathological characteristics, as well as survival data of prostate SCC from Surveillance, Epidemiology, and End Results datasets.
A total of 260 patients with prostate SCC were selected from the SEER database of the National Cancer Institute between 2004 and 2015. Age-adjusted incidence rates, the observed and relative survival rates were evaluated over time by the SEER*Stat Software version 8.3.5. Overall survival rates that stratified by summary stage and treatment effects were evaluated by Kaplan-Meier method. The significant differences were assessed in a log-rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS.
Prostate SCC is a highly malignant cancer and our analysis of recent data has shown its incidence is increasing. Incidence rate of metastatic prostate SCC has increased and the survival rates have worsened in recent years. However, chemotherapy shows some survival benefit for prostate SCC patients with regional and distant metastasis over other treatment methods. Further work is needed to understand the reason prognosis of this type prostate cancer is worsening.
Cancer medicine. 2019 Sep 13
Jili Wang, Xiaoyan Liu, Yan Wang, Guoping Ren
Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
What Is A 5
A relative survival rate compares people with the same type and stage of cancer to people in the overall population. For example, if the 5-year relative survival rate for a specific stage of lung cancer is 60%, it means that people who have that cancer are, on average, about 60% as likely as people who dont have that cancer to live for at least 5 years after being diagnosed.
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Large Cell Prostate Cancer
Large cell prostate cancer is very rare. Because of this, we dont yet know how it develops, or the best ways to treat it.
It is aggressive and can spread quickly to other parts of the body. Most men who have large cell prostate cancer also have common prostate cancer at the same time. And its most common in men whove already had hormone therapy for normal prostate cancer.
Because neuroendocrine cells dont produce PSA, most men with large cell prostate cancer have a low PSA level. So a PSA test cant be used to diagnose or monitor your cancer. But if you have both large cell prostate cancer and common prostate cancer at the same time, you may have higher PSA levels. More research is needed before we can know whether PSA tests can help to diagnose large cell prostate cancer mixed with common cancer.
Most large cell prostate cancers are diagnosed when they have grown large enough press against the urethra , which can cause difficulty urinating . So large cell prostate cancer is often diagnosed when men have surgery called transurethral resection of the prostate to treat their urinary problems. Tissue removed during surgery is looked at under the microscope to confirm you have large cell prostate cancer. You will also need scans to see if your cancer has spread.
Most men with large cell prostate cancer have chemotherapy . You may also be offered surgery and radiotherapy, depending on how much the cancer has grown and spread.
Clinical Information Of The Patients Reported In Literatures
The 26 cases were aged from 21 to 82 years . Because the median age was 61 years, patients were divided into two groups: < 59 years old and 60 years old. There were 15 cases in the 60 group . Most cases suffered from difficulty urinating, and 20 cases showed normal serum PSA levels. DRE indicated grade III prostate enlargement and hardening. Space-occupying lesions were detected by imaging examinations. Among them, 11 cases underwent prostate biopsies eight underwent transurethral resection of the prostate and seven underwent radical prostatectomy. For postoperative treatment, 13 cases received chemotherapy, two received radiotherapy, and 13 had a history of endocrine therapy .
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Patient And Disease Variables
In our study cohort, the median age at diagnosis was 70 6276) . Survival data were available for 197 patients with a median follow-up time of 14 months and a total of 158 deaths. A majority of patients were white , lived in a metropolitan area and received treatment at a comprehensive cancer program . The year of diagnosis and region of diagnosis were evenly distributed across the study period. For patients with known CCI, the majority had CCI of 0 . Of the patients diagnosed after 2003, the median PSA was 4.9ngml1 and 61% presented with elevated measurements . Among men with recorded clinical T stage, 73% were staged cT12.
Table 1 Patient, hospital and clinical characteristics
Lung Cancer Survival Rates
Survival rates can give you an idea of what percentage of people with the same type and stage of cancer are still alive a certain amount of time after they were diagnosed. They cant tell you how long you will live, but they may help give you a better understanding of how likely it is that your treatment will be successful.
Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Talk with your doctor about how these numbers may apply to you, as he or she is familiar with your situation.
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Tyrosine Kinase And Angiogenesis Inhibitors
The tyrosine kinase receptor family comprises around 20 different classes including platelet-derived growth factor receptors , c-kit and epidermal growth factor receptor . Targeting PDGFR/c-kit, for example, using agents that are used in acute myelogenous leukemia such as imatinib mesylate, has been disappointing. Sunitinib, an oral tyrosine kinase inhibitor with action against all vascular endothelial growth factor receptor , PDGFR, stem cell factor receptor and FMS-like tyrosine kinase-3, has shown some promise in phaseII studies . One hundred and seven patients received sunitinib with 16.7% of pancreatic NETs achieving objective response, 68% achieving stable disease median time to progression 7.7 months in pNETs, 10.2 months in midgut NETs. The recent phase III study of sunitinib versus placebo in slowly progressing pNETs was halted due to an unplanned early analysis showing significant benefit with PFS of 11.4 months with Sunitinib versus 5.5 months with placebo .
Sorafenib, a small molecule inhibitor of Raf kinase, VEGFR-2 and PDGFR tyrosine kinase domains, has been explored in metastatic NETs with 10% partial response and 29% minor response in 41 patients. However, 43% in this study developed grade 3-4 toxicity .