What You Need To Know About The Prostate Metastatic Castration
A enlarged prostate can also cause blockages in the urethra. A blocked urethra can also damage the kidneys. A patient suffering from an enlargement of the prostate may have pain in his lower abdomen and genitals. If pain is present, a digital rectal examination will reveal hard areas. A doctor may prescribe surgery or perform an endoscopic procedure. If the enlarged prostate is not completely removed, it will shrink.
While the size of an enlarged prostate will influence the extent of urinary symptoms, men may experience a range of urinary symptoms. Some men have minimal or no symptoms at all. Some men will have a very enlarged prostate, whereas others will have a mild enlargement. Generally, the symptoms can stabilize over time. Some men may have an enlarged prostate but not notice it. If they have an enlarged colon, their physician can perform a TURP procedure.
Aua 201: Survival Rates And Economic Outcomes In Chemotherapy
- Mean all-cause outpatient costs PPPM
- Mean total costs PPPM
- Prostate cancer-related outpatient costs PPPM
- Mean total costs PPPM
- In this real-world analysis, patients prescribed enzalutamide compared to abiraterone acetate had great median overall survival, reduced risk of death, fewer prostate cancer outpatient visits and shorter inpatient length of stay, as well as lower all-cause and prostate cancer-related health care costs
- As a limitation, Dr. George notes that this study was restricted by the factors available in the claims data and that other factors not included in the analysis may affect survival
Dose Determination Dosimetry And Administration
Dose determination of 225Ac-PSMA was established by Kratochwil et al. , based on time-activity curves that made use of dosimetry estimates obtained from serial 177Lu-PSMA scans obtained post-therapy which were then extrapolated to the physical half-life of 225Ac. Fourteen patients were divided into four groups with different empirical doses for salvage therapy as follows: 50kBq/kg , 100 kBq/kg , 150kBq/kg and 200 kBq/kg . Treatment response and the presence of any toxicity was retrospectively evaluated. Results indicated the highest radiation dose was received by the salivary glands , followed by the kidneys and the bone marrow . The researchers found that xerostomia became the dose-limiting factor at treatment activities above 100 kBq/kg/cycle. Therapy administered at a dose of 100 kBq/kg resulted in a significant decline in s-PSA, which had a duration of less than 4 months, which was then improved with further cycles administered every two months. Administered activities of 50 kBq/kg resulted in a poor tumor control with no occurrence of side effects. Based on the aforementioned data, 100 kBq/kg/cycle was determined as the optimal dose for human use with intervals of eight weeks in-between doses . A recently published image of the month demonstrated the feasibility of image-based dosimetry with 225Ac-PSMA quantitative SPECT . Micro dosimetry calculations have also been calculated with Monte Carlo simulations .
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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 prostate cancer is 90%, it means that men who have that cancer are, on average, about 90% as likely as men who dont have that cancer to live for at least 5 years after being diagnosed.
Castration Resistant Prostate Cancer Incidence
Zhang et al. use evolution-guided mathematical models to guide the timing and dosing of abiraterone treatment in castrate-resistantprostatecancer. While the sample size is limited, the implications of the study outcome are broad and compelling, and the article importantly highlights the transformative potential of deeply interdisciplinary.
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Targeted Radiotherapy Extends Survival In Metastatic Castration
Morris MJ, et al. Abstract LBA4. Presented at: ASCO Annual Meeting June 4-8, 2021.
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An investigational targeted radioligand therapy improved outcomes for certain men with advanced prostate cancer, according to randomized phase 3 study results to be presented during the plenary session of the virtual ASCO Annual Meeting.
The addition of lutetium-labeled PSMA-617 to best standard care significantly prolonged OS and PFS for men with prostate-specific membrane antigen -positive, metastatic castration-resistant disease.
The agent commonly called 177Lu-PSMA-617 also appeared well-tolerated.
The findings support adoption of 177Lu-PSMA-617 as a new treatment option for this patient population pending FDA review, according to Michael J. Morris, MD, clinical director of the genitourinary medical oncology service and prostate cancer section head in the division of solid tumor oncology at Memorial Sloan Kettering Cancer Center.
Michael J. Morris
A sizable number of men face the dilemma of what to do when they have completed androgen receptor-directed therapies and chemotherapy and their disease is still growing, Morris told Healio. There is no group of men with prostate cancer in higher need, and this introduces a life-prolonging therapy for them.
Central review of 68 Ga-PSMA-11 scans determined PSMA positivity.
Median follow-up was 20.9 months.
What Is Metastatic Castration
Metastatic castration-resistant prostate cancer and its precursor, metastatic hormone sensitive prostate cancer , are advanced forms of the condition that dont respond to initial treatments, such as surgery and hormone therapy, and have started to spread beyond the prostate.
The type mCRPC differs from mHSPC in that the latter disease still responds to standard hormone treatment called androgen deprivation therapy , even though it has spread to other parts of the body. Specifically, the castration-resistant form mCRPC is particularly dangerous and leads to a very poor prognosis.
Impact Of Age At Diagnosis On Outcomes In Men With Castrate
Michael R Humphreys1, Kimberly A Fernandes2, Srikala S Sridhar3
1. Division of Medical Oncology, British Columbia Cancer Agency, Vernon, BC, Canada 2. Department of Biostatistics, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada 3. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.
Corresponding author: Srikala S. Sridhar MD MSc FRCPC, Medical Oncologist, Princess Margaret Hospital, Assistant Professor, University of Toronto. 5-222, 610 University Avenue, Toronto, ON, Canada M5G 2M9, TEL: 416-946-4501 2662 FAX: 416-946-6546. Srikala.Sridharca.More
Btime From Crpc To Death
At the time of data-lock, 77% deaths were observed. The median time from CRPC to death was 2.9 yrs. There was no statistically significant difference in OS between the age stratified cohorts . The key factors that were independently predictive of adverse survival from CRPC to death were presence of visceral metastasis, absolute PSA nadir on ADT , time to PSA nadir on ADT , and duration of hormone sensitivity determined by time from starting a gonadotropin releasing hormone agonist to CRPC . Anti-androgen withdrawal response occurred in 26% of patients and did not impact OS. There was no discernible difference between patients receiving docetaxel compared to no chemotherapy, but CRPC patients receiving non-docetaxel chemotherapy exhibited a reduced survival . Variables measured at diagnosis did not influence survival from CRPC. We also found that age < 55 at the time of CRPC diagnosis was associated with a trend to increased risk of death on univariate analysis but not on multivariate analysis .
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Pairwise Comparison With Crossover To Nht Only
Median follow-up among patients who crossed over was 19.30 months in the enzalutamide subset and 21.40 months in the abiraterone subset. Median treatment duration was similar in enzalutamide patients who switched to abiraterone versus abiraterone patients who switched to enzalutamide . After baseline covariate adjustment, OS was comparable across subsets with an adjusted HR of 1.10 with comparable median OS of 27.20 months in the enzalutamide to abiraterone subset versus 28.53 months in the abiraterone to enzalutamide subset .
Treatments To Control And Prevent Symptoms Caused By The Spread Of Prostate Cancer To The Bones
Palliative External beam radiotherapy
Radiopharmaceuticals: Strontium-89 , samarium-153
Radium-223 dichloride is now licensed and called Xofigo. This is not widely available in the UK but BPC is one of a relatively small number of specialist centres using this treatment.
Zolidronic acid is a bisphosphonate given by a 15-minute intravenous infusion every 34 weeks. It reduces the risk of bone complications, including pain and fractures.
Xgeva : this is a newly licensed drug available at BPC.
Surgery may be undertaken to treat bone fractures or to relieve the pressure on the spinal cord by bone metastases.
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Chemotherapy Overall Survival Subset Analysis
A subset analysis of 246 chemotherapy treated patients, with average follow-up of 1.1 yrs, observed 193 deaths. The median survival was 55 weeks with no differences on the basis of age stratification. Median PFS was 24.4 wks and median PSA-PFS was 26 wks, respectively, with no statistical difference between age groups. On multivariate analysis of significant covariates, PSA doubling time of less than 1 month, ECOG PS 3, and baseline Hgb less than 100 g/L were consistent predictors of shorter OS, PFS, and PSA-PFS. Elevated LDH was an important predictor of OS but not PFS or PSA-PFS. Treatment with docetaxel chemotherapy was statistically protective versus non-docetaxel based regimens for both OS and PFS on multivariate analysis .
Clinical Evidence With 225ac
Clinical evidence has been limited mostly to retrospective observational studies at this point, with the majority of treated patients having received 225Ac-PSMA in a salvage therapy setting. A paper by Kratochwil and colleagues evaluated tumor control duration and efficacy in a group of 40 patients with metastatic castrate-resistant prostate cancer. A dose of 100 kBq/kg was administered at intervals of two months for three cycles, and six-month follow-up evaluation performed with PSMA-based PET or SPECT imaging. Interim evaluations consisted of s-PSA and full blood count results, done monthly.
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Symptomatic treatment of an enlarged prostate usually involves a combination of medication and lifestyle changes. A diet rich in fruits and vegetables may be the best option if you suffer from chronic urination. It will help the body adjust to the increased size of the prostate. Also, taking regular urination intervals will help retrain the bladder to function properly. Inactivity also contributes to urine retention, and cold temperatures can increase the urge to urinate.
Invasive treatment of enlarged prostate includes medication that relieves the pressure on the urethra and bladder. However, if the condition is severe, it may require surgical intervention. If treatment is not successful, the enlarged prostate can become a potentially life-threatening disease. As the hormone levels in the body change, the enlarged prostate can lead to various complications, including urinary retention and even cancer. This is why it is critical to see a doctor for further evaluation.
Pairwise Comparison With Switching To Other Sequential Regimens
Median follow-up in the enzalutamide subset for patients who switched from enzalutamide to multiple other sequential therapies was 24.03 months and 29.00 months in the abiraterone subset. Pairwise comparison of patients switching to other sequential therapies demonstrated similar OS in the enzalutamide subset versus the abiraterone subset .
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Pairwise Comparison In The Overall Population
Overall, median follow-up was similar: 18.27 months in the enzalutamide cohort and 19.07 months in the abiraterone cohort . Median enzalutamide treatment duration was 9.93 months versus 8.47 months with abiraterone. After adjusting for age, race, individual comorbidities, and pre-index treatments, enzalutamide-treated patients had a 16% lower risk of death versus abiraterone-treated patients . Median OS was longer in the enzalutamide cohort versus the abiraterone cohort .
Fig. 2: Adjusted KaplanMeier curve for overall survival in all patients with chemotherapy-naive mCRPC treated with either enzalutamide or abiraterone irrespective of follow-up treatments.
*Enzalutamide versus abiraterone. ABI abiraterone, ENZA enzalutamide, HR hazard ratio, IQR interquartile range, mCRPC metastatic castration-resistant prostate cancer, OS overall survival.
Early Evidence Regarding Combinations Of Parp Inhibitors With Standard Mcrpc Therapies
There is conflicting evidence supporting the use of PARP inhibitors in mCRPC patients without mutations in DNA repair genes. The potential utility of PARP inhibitors in this setting will likely only be in combination with another effective agent. Preclinical studies have shown that inhibiting the androgen pathway can induce cell sensitivity to PARP inhibition, suggesting a synergy between androgen pathway blockade and PARP inhibitorsforming the hypothesis of multiple clinical trials . Ongoing phase 2/3 controlled clinical trials investigating PARP inhibitors in mCRPC with or without the concurrent administration of another agent have been summarized .
Table 1 Ongoing phase 2/3 controlled trials investigating PARP inhibitors in mCRPC
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Remission And The Chance Of Recurrence
A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having no evidence of disease or NED.
A remission can be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. Although there are treatments to help prevent a recurrence, such as hormonal therapy and radiation therapy, it is important to talk with your doctor about the possibility of the cancer returning. There are tools your doctor can use, called nomograms, to estimate someone’s risk of recurrence. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.
In general, following surgery or radiation therapy, the PSA level in the blood usually drops. If the PSA level starts to rise again, it may be a sign that the cancer has come back. If the cancer returns after the original treatment, it is called recurrent cancer.
When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence, including where the recurrence is located. The cancer may come back in the prostate , in the tissues or lymph nodes near the prostate , or in another part of the body, such as the bones, lungs, or liver . Sometimes the doctor cannot find a tumor even though the PSA level has increased. This is known as a PSA recurrence or biochemical recurrence.
Metastatic Hormone Sensitive Prostate Cancer
This form of prostate cancer can be an initial diagnosis but more often refers to cases where surgeries or other initial treatments to remove tumors from the prostate havent succeeded in stopping its progression.
Notably, too, these cases are defined by metastasis, meaning it has started to spread to other structures in the body, such as bones or the lymph nodes. However, the development of castration resistance is part of the eventual and expected progression of the diseaseeven while on ADT.
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The Initial Causes Metastatic Castration
One of the first symptoms of prostate issues is pain or tenderness in the groin or lower back. This can be the result of a noncancerous condition called enlarged prostatic tissue, or it could be an infection of the bladder. In either case, its important to see a doctor as soon as possible. If youre suffering from prostate pain, you may want to consider reducing your caffeine intake.
Another symptom of a potentially enlarged prostate is difficulty starting a stream of urine, leaking, or dribbling. These symptoms are not serious, but theyre still alarming. Most men put up with an enlarged prostate for years before seeking medical attention, but they typically seek treatment as soon as they notice symptoms. Even if you dont have symptoms, its worth getting checked to determine if you have any prostate issues.
If you experience nightly bathroom runs, you may be experiencing an enlarged prostate. You may be having difficulty starting a stream of urine, or you may even be dribbling or leaking during the day. These problems arent life-threatening, but can become a nuisance. You should not ignore these signs and seek treatment as soon as you notice them. If you feel any of these symptoms, you should consult a doctor.
Balance Of Efficacy And Toxicity
Serious adverse events were observed in 30%-60% of patients receiving combination therapies.911,23,25 The toxicity may exceed the benefits in some patients. Increased medical expense with combination therapies is also an issue.
Some metastatic patients are also shown to achieve long-term survival with ADT alone. For example, patients with low-volume and low-risk mCSPC who achieved PSA 2 ng/mL at 3 mon after ADT commencement had a considerably long OS of 112 mon with ADT with or without first-generation antiandrogens.33 It is very likely that upfront combination therapy using docetaxel and ARPIs would be excessive for these patients. The profile of adverse events and medical cost are different among agents. For example, docetaxel is cheaper than ARPIs, but it is associated with neutropenia and peripheral neuropathy.5 ENZ increases the risk of fatigue, hypertension, cardiovascular event, and seizure.9,10,34 Abi is associated with hypertension, cardiovascular events, and hypokalemia.23,34 Rash is relatively common adverse event of APA.11 Therefore, treatments must be tailored according to the individual patients profile, comorbidities and preferences, and it is crucial to choose the appropriate treatments for each patient while avoiding unnecessary overtreatment. All-comers therapeutic approaches may not be used anymore in clinical practice.
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From Personalized To All
A systematic review and meta-analyses of the aggregate data of the CHAARTED, GETUG-AFU15, and STAMPEDE trials indicated that the upfront use of docetaxel showed better OS in patients with mCSPC than in those with ADT alone .24 As per the STAMPEDE trial, upfront docetaxel improved the OS irrespective of the metastatic tumor burden .25 For low-volume patients, the median OS was 93.2 mon and 76.7 mon for upfront docetaxel and ADT alone, respectively . This HR was consistent with that in high-volume patients , suggesting that upfront docetaxel would be beneficial for all patients with mCSPC, irrespective of the metastatic burden, and this treatment may be for all-comers.
These recent clinical trials suggest that early combination therapies are consistently associated with better outcomes than ADT alone, irrespective of the tumor burden and risk category. Thus, recent clinical guidelines recommend a combination of docetaxel or ARPIs with ADT as first-line therapy for all patients with mCSPC.13,14 The era of ADT alone may end and upfront combination therapies are becoming a standard of care as the initial treatment for all-comers with mCSPC.