Genomic Alterations In T
Unlike other small cell neuroendocrine carcinomas and their non-small cell histologic counterparts, there is a surprising overlap in the spectrum of genomic alterations seen in t-SCNC and mCRPC-adenocarcinoma. Similar numbers of single nucleotide and copy number variants are observed across t-SCNC and mCRPC-adenocarcinoma specimens, and most of the common PC alterations are detected in similar frequencies across the two histologic subtypes. This genomic overlap supports a divergent model of clonal evolution, whereby t-SCNC arises through transdifferentiation of an mCRPC-adenocarcinoma subclone – rather than treatment selection of a pre-existing independent neuroendocrine subclone. The paucity of genomic differences between mCRPC-adenocarcinoma and t-SCNC also underscores the potential role of epigenetic reprogramming in mediating lineage plasticity and establishing tumor phenotype, discussed below. In the context of this broad genomic overlap, however, the few genomic differences that have been described across the two histologic subtypes provide important insights into the pathogenesis of t-SCNC.
Gene Expression Profiling Of Scpc/lcnec Xenografts Reveals Upregulation Of Mitotic Genes
Unsupervised hierarchal clustering of the raw expression profiles obtained from the MDA PCa 79, 117-9, 130, 144-13, 144-4, 146-10, 155-2, and 155-12 xenografts showed that replicates from the same xenograft clustered together, reflecting biologic identity, and that the xenografts were classified according to their morphology and AR expression .
SCPC/LCNEC xenografts were collectively compared against the adenocarcinoma xenografts. We identified 140 probes expressed differently , corresponding to 104 unique RefSeq Transcript IDs . Gene Ontology analysis showed enrichment in mitosis-related biologic process subtrees, including âcell-cycle phaseâ , âmitotic cell cycleâ , and âcell divisionâ , among the 104 genes expressed differently between the groups . Genes in these subtrees included CDC25C , ANLN , AURKA , HELLS , UBE2C , PTTG1 , KPNA2 , TACC3 , PDCD6IP , HIST1H4C , and PCNA .
Does Atezolizumab Boost Survival With Chemotherapy In Small Cell Or Neuroendocrine Carcinoma Of The Prostate
A correlation between small cell or neuroendocrine carcinoma of the prostate and poor survival outcomes was revealed, despite treatment with the combination of the immunotherapy agent atezolizumab and chemotherapy, according to an institutional study conducted within the Mayo Clinic.
A correlation between small cell or neuroendocrine carcinoma of the prostate and poor survival outcomes was revealed, despite treatment with the combination of the immunotherapy agent atezolizumab and chemotherapy, according to an institutional study conducted within the Mayo Clinics Division of Medical Oncology.
The exploration of this combination in prostate cancer was influenced by the survival benefit observed with atezolizumab and chemotherapy in patients with extensive-stage small cell lung cancer . It is a common clinical practice to use regimens from the SCLC space to treat rare extrapulmonary small cell carcinoma, therefore oncologists at the Mayo Clinic sought to test the treatment strategy in their institution.
Recent introduction of checkpoint inhibitor therapy for SCC of the prostate was based on extrapolation from studies in small-cell lung cancer. We wanted to review the outcomes for such patients who had received chemo-immunotherapy treatment at Mayo Clinic, the study lead Lance C. Pagliaro, MD, professor of oncology, Division of Medical Oncology, Department of Oncology at Mayo Clinic, told Targeted Oncology in an interview.
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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
Coping With Small Cell Prostate Cancer
Coping with a rare condition can be difficult, both practically and emotionally. Being well informed about the cancer and its treatment can help you to make decisions and cope with what happens. It can also help to talk to other people who have the same condition.
You can visit Cancer Chat Cancer Research UK’s discussion forum. It is a place for anyone affected by cancer to share experiences, stories and information with other people who know what you are going through.
Small cell carcinoma of the prostate R Nadal and others Nature Reviews Urology, 2014. Vol 11, Issue 4, Pages 213-219
The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours.P Humphrey and othersEuropean Association of Urology, 2016
Not such a small diagnosis: small cell carcinoma of the prostateA Rauf and othersJournal of Surgical Case Reports, 2020. Vol 2020, Issue 6.
Poorly differentiated small cell type neuroendocrine carcinoma of the prostate: a case report and literature reviewK Kumar and others
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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.
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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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:
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.
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Modeling A Lethal Prostate Cancer Variant With Small
Note: Supplementary data for this article are available at Clinical Cancer Research Online .
S.N. Maity and A. Aparicio contributed equally to this work and are co-senior authors.
The genomic and transcript profiling data have been deposited into NCBI/GEO under superseries GSE33054.
Vassiliki Tzelepi, Jiexin Zhang, Jing-Fang Lu, Brittany Kleb, Guanglin Wu, Xinhai Wan, Anh Hoang, Eleni Efstathiou, Kanishka Sircar, Nora M. Navone, Patricia Troncoso, Shoudan Liang, Christopher J. Logothetis, Sankar N. Maity, Ana M. Aparicio Modeling a Lethal Prostate Cancer Variant with Small-Cell Carcinoma Features. Clin Cancer Res 1 February 2012 18 : 666â677.
Clinical And Pathological Information Of The Cases From Plagh
In total, 1,002 cases of prostate cancer were diagnosed pathologically at the Chinese PLA General Hospital from 1999 to 2011, and seven of them were suspected of SmCC. All pathologic sections from these seven cases were reviewed by three pathologists. Immunohistochemical staining for prostate-specific antigen , CD56, synaptophysin , chromogranin A , and cytokeratin was performed. Four cases were excluded because of the negative staining for CD56, Syn, and CgA, which were suspected to be poorly differentiated acinar adenocarcinomas with Gleason scores 9-10. The remaining three cases were confirmed as SmCC. Detailed clinical and pathological information is presented below.
Case 1. Mixed SmCC. Components of SmCC. Components of acinar adenocarcinoma. Gleason scores were 3+3=6 combined with bilateral lung and liver metastases.
Case 2. A 65-year-old patient was referred to our hospital with symptoms of dysuria and frequent urination. The serum PSA level was 20.67ng/mL . DRE indicated the prostate was homogeneously enlarged and the central sulcus disappeared. MRI showed a mass in the prostate, combined with pelvic lymph node metastasis. He underwent an ultrasound-guided prostate biopsy. Combined SmCC and acinar adenocarcinoma were confirmed pathologically. The patient received endocrine therapy. The 4-month follow-up showed tumor-bearing survival, and the general condition of the patient was poor.
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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.
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Scpc/lcnec Xenografts Lack Cyclin D1 And Rb Expression
Visual analysis of hematoxylin and eosin stains revealed higher number of mitotic figures and Ki-67 expression in the SCPC/LCNEC xenografts relative to the adenocarcinoma which might suggest that the M-phase gene overexpression is a mere reflection of the increased proliferation of SCPC/LCNEC tumors. However, except for 144-13 the growth rate of the SCPC/LCNEC xenografts was not significantly different from that of the adenocarcinoma xenografts . It has been shown that not all cells containing the Ki-67 antigen are actively proliferating cells and that tumor cells can remain positive for Ki-67 even when arrested in G1/S or G2/M . Indeed, flow cytometry analysis showed that the SCPC 146-10 xenograft contained a higher proportion of cells in G2/M phase compared with the adenocarcinoma 180-30 xenograft, whereas the proportion of cells in S-phase was similar in both , suggesting that the overexpression in UBE2C and other mitotic genes could reflect an accumulation of cells in mitosis rather than increased proliferation.
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Genomic Characterization Of Treatment
Ivan de Kouchkovsky1David A. Quigley2Eric J. Small1Rahul Aggarwal1
1Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA.
2Department of Urology, University of California San Francisco, San Francisco, CA 94143, USA.
Correspondence to: Dr. Ivan de Kouchkovsky, Department of Medicine, University of California San Francisco, 550 16th Street, Box 3211, San Francisco, CA 94158-3211, USA. E-mail: Ivan.deKouchkovsky@ucsf.edu
Available online: Academic Editor: Copy Editor:Production Editor:
© The Author 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Deadly Form Of Advanced Prostate Cancer Is Common Calls For Distinct Treatment
- University of California San Francisco
- 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.
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Treatment By Cancer Type
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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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