Performance Status And Predicted Life Expectancy
Performance status and predicted life expectancy are both critical elements to incorporate into individualized clinical decision-making in men with advanced prostate cancer. Performance status remains a key factor in treatment decision-making, particularly among men with advanced prostate cancer. Indeed, performance status has been found to be strongly associated with survival among men with mCRPC, 35-38 and has been used to define index patients in prior versions of this guideline. Performance status generally describes an individual patientâs level of functioning and how oneâs disease impacts a patientâs activities of daily living. The first of two commonly used scales to evaluate performance status include the Eastern Cooperative Oncology Group scale from 0 to 5 where 0 is fully functional and 5 is dead. The second is the Karnofsky scale where 10 represents a moribund individual and 100 represents an individual with no limitations.
Assessing Metastases And Local Recurrence
Once BCR has been detected, it is important to try to establish whether this represents local recurrence or disseminated disease, or both, in order to guide subsequent treatment decisions. Importantly, metastatic disease must be acceptably ruled out before subjecting patients to local salvage treatment, owing to the significant morbidity associated with such treatments. Regardless of whether BCR is detected post-RP or post-RT, the same principles of imaging apply.
Multidisciplinary Nature Of Treatment In Todays Advanced Prostate Cancer Care Paradigm
As the therapeutic landscape evolves to include increasingly complex combinations of systemic therapies with or without local therapies, advances in imaging, and germline and somatic genetic testing, treating men with advanced prostate cancer is increasingly one that must embrace multidisciplinary management approaches. Team members should include urologists, medical oncologists, and radiation oncologists at a minimum when supporting treatment decisions for advanced disease. Additional specialists may also include genitourinary pathology, genetic counseling, palliative care, and holistic specialists, as appropriate, in addition to primary care. Best practices must also include clinicians comfortable describing the use of germline and somatic genetic testing, and when advanced imaging techniques could be optimally used or avoided. Radiologists and nuclear medicine specialists are valuable in helping to accurately interpret scans. Palliative care team members may also play a key role when treating men with symptomatic metastatic disease. Palliative care itself is an interdisciplinary, holistic approach to managing an advanced disease such as prostate cancer with a guarded prognosis. It can include controlling symptoms that are physical, psychological, spiritual, and social. The goal of palliation is to prevent and relieve suffering and to support the best possible QOL for the patient and family.
Justification For A New Guideline
Clinicians treating men with advanced prostate cancer are challenged with the rapidly evolving prostate cancer landscape given the approval of new classes of agents for use in various prostate cancer disease states. The increasing complexity of advanced prostate cancer management underscores the need for the current clinical practice guideline, developed to provide a rational basis for treatment of patients with advanced disease, based on currently available published data. To assist in clinical decision-making, guideline recommendations are furnished according to disease state across the entire continuum of advanced prostate cancer.
Cancer That Is Thought To Still Be In Or Around The Prostate
If the cancer is still thought to be just in the area of the prostate, a second attempt to cure it might be possible.
After radiation therapy: If your first treatment was radiation, treatment options might include cryotherapy or radical prostatectomy, but when these treatments are done after radiation, they carry a higher risk for side effects such as incontinence. Having radiation therapy again is usually not an option because of the increased potential for serious side effects, although in some cases brachytherapy may be an option as a second treatment after external radiation.
Sometimes it might not be clear exactly where the remaining cancer is in the body. If the only sign of cancer recurrence is a rising PSA level , another option for some men might be active surveillance instead of active treatment. Prostate cancer often grows slowly, so even if it does come back, it might not cause problems for many years, at which time further treatment could then be considered.
Factors such as how quickly the PSA is going up and the original Gleason score of the cancer can help predict how soon the cancer might show up in distant parts of the body and cause problems. If the PSA is going up very quickly, some doctors might recommend that you start treatment even before the cancer can be seen on tests or causes symptoms.
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The Frequency Of Bcr Cp Crd And Rates Of Bpfs Cpfs Css
Median time of follow-up after RP was 64 months. Over this time, 207 men experienced BCR. One hundred twenty-seven men had BCR in the following year after RP, 27 in the second year, 16 in the third, 14 in the fourth, 7 in the fifth, and 16 patients had BCR after 5 years . Of 207 men, 181 received salvage radiotherapy or hormone therapy or both sRT + HT due to BCR.
Figure 1. Risk of biochemical recurrence by the following year after radical prostatectomy .
CP was diagnosed in 49 cases. Median time from BCR to CP was 17 months. Twelve men had metastases in lymph nodes, 11 had metastases in bones, 19 had metastases in lymph nodes and bones, 1 had visceral metastases, and 6 had local recurrence in the surgical bed. During the follow-up, 72 patients died. In 24 cases PCa was the cause of death.
According to the D’Amico risk classification, the 5-year BPFS rate after RP of patients with one risk factor was 57.7%, and that with two factors was 34.4%. All patients with three risk factors had BCR in the first 5 years after RP .
In all study cohorts, 5- and 10-year BPFS rate was 49.2 and 34.2%, respectively. CPFS rate was 89.2 and 81% and CSS rate was 95.6 and 90.1%, respectively.
Neoadjuvant And Adjuvant Hormonal Therapy With Rt
A consideration of the role of adjuvant therapy with RT is useful before examining the treatment choices in the setting of BCR after RT. The combination of RT with gonadotrophin-releasing hormone ADT is proven to be superior to RT alone followed by deferred ADT upon BCR . Use of adjuvant or neoadjuvant ADT with RT in patients with locally advanced PCa is now standard practice.
A meta-analysis showed that for localised and locally advanced PCa, neoadjuvant ADT before RT significantly improved biochemical disease-free survival and clinical disease-free survival . For patients with a Gleason score of 26, neoadjuvant ADT before RT significantly improved OS, and a short duration of neoadjuvant ADT should therefore be considered in such patients .
While the evidence strongly favours neoadjuvant/adjuvant therapy in patients with locally advanced PCa , the value of this approach in intermediate- or high-risk localised PCa is less clear . Rates of BCR may be reduced with adjuvant or neoadjuvant ADT in carefully selected patients with intermediate- or high-risk localised PCa , and the decision to use adjuvant or neoadjuvant ADT with RT in such patients should therefore be based upon individualised assessment.
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Searches And Article Selection
A research librarian conducted searches in Ovid MEDLINE , Cochrane Central Register of Controlled Trials , and Cochrane Database of Systematic Reviews . An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.
The methodology team developed criteria for inclusion and exclusion of studies based on the Key Questions and the populations, interventions, comparators, outcomes, and settings of interest. The population was patients with advanced prostate cancer as described in Table 3. Treatments included first and second line antiandrogens, immunotherapy, chemotherapy, radiation therapy, surgery, radiopharmaceuticals, and surveillance strategies. Comparisons were against placebo, no therapy, or another active intervention and intermittent versus continuous therapy. Outcomes included overall survival , prostate cancer mortality, progression-free survival , prostate-specific antigen progression-free survival , failure-free survival, metastases-free survival, time to metastases, time to progression, skeletal events, and adverse events.
Cvaccine Plus Radiation Therapy
Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy, perhaps due to occult metastatic disease. Thirty patients were randomized into vaccine plus radiotherapy or radiotherapy-only arms . Thirteen of 17 patients in the combination arm had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm . There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing . Another study in men with localized prostate cancer investigated whether the vaccination with rV-PSA/rV-B7.1 prime and rF-PSA boosters induced immune responses to additional TAAs. Western blotting revealed treatment-associated autoantibody responses in 15 of 33 patients treated with vaccine + radiotherapy versus 1 of 8 treated with radiation alone.
BSBrock R. Baker, … MD, MPHRonald C. Chen, in, 2016
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Additional Treatment After Surgery
Additional treatment can come with one of two approaches: treatment given as adjuvant therapy , or as salvage therapy . In the modern era, most additional treatment is given as salvage therapy because firstly this spares unnecessary treatment for men who would never experience recurrence, and secondly because the success rates of the two approaches appear to be the same.
Regardless of whether an adjuvant or salvage therapy approach is taken, the main treatment options following biochemical recurrence are:
- Radiotherapy this is the commonest approach. Because scans dont show metastatic deposits until the PSA is more than 0.5 ng/ml and because radiotherapy is more effective when given before this level is reached, the radiotherapy energy is delivered to the prostate bed. This is because we know that this is the commonest site of recurrence in most men, and that 80% of men treated in this way will be cured.
- Active surveillance this is appropriate for a very slowly-rising PSA in an elderly patient who has no symptoms.
- Hormonal therapy in many ways this is the least appealing option as it causes symptoms but does not cure anyone, although it does control the recurrence and lower the PSA.
Differences Among Risk Groups
Men with PCa have been classified into low-, intermediate- and high-risk Groups for tumor recurrence and disease specific mortality, based on PSA level, clinical or pathological staging and GS. High-risk patients have PSA level 20ng/mL or GS 8 or clinical/pathological stage T2c . Lymph-node positive and PSM have also been reported as poor prognosis factors.
Risk Group classification predicts biochemical and clinical progression as well as PCa specific mortality and overall survival. The risk of disease progression in these groups has been validated for patients submited to RP in many studies. In patients from Mayo Clinic, BCR rates were 2.3 and 3.3-fold greater in high and intermediate-risk in comparison with low-risk patients, respectively. In those patients, mortality rates in high and intermediate-risk patients were greater than 11 and 6-fold over low-risk men .
Therefore, it is crutial to understand the role of each clinical and pathologic feature in PCa BCR and disease progression.
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What Types Of Hormone Therapy Are Used For Prostate Cancer
- reducing androgen production by the testicles
- blocking the action of androgens throughout the body
- block androgen production throughout the body
Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer and the first type of hormone therapy that most men with prostate cancer receive. This form of hormone therapy includes:
Treatments that block the action of androgens in the body are typically used when ADT stops working. Such treatments include:
Treatments that block the production of androgens throughout the body include:
Treatments For Recurrent Prostate Cancer
Recurrent prostate cancer is cancer that comes back after it has been treated. Recurrent prostate cancer is also diagnosed when theprostate-specific antigen level starts to rise quickly after initialtreatment but there are no other signs of cancer. This is called a biochemicalrecurrence or PSA failure.
The following aretreatment options for recurrent prostatecancer. Your healthcare teamwill suggest treatments based on your needs and work with you to develop atreatment plan. The type of treatment that you receive will depend on:
- the treatments you’ve already had
- where the cancer comes back
- whether the cancer has spread
- your overall healthand whether you have other illnesses
- your age and life expectancy
- your personal preferences
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How Will I Know That My Hormone Therapy Is Working
Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual mans prostate cancer. Therefore, men who take hormone therapy for more than a few months are regularly tested to determine the level of PSA in their blood. An increase in PSA level may indicate that a mans cancer has started growing again. A PSA level that continues to increase while hormone therapy is successfully keeping androgen levels extremely low is an indicator that a mans prostate cancer has become resistant to the hormone therapy that is currently being used.
Neoadjuvant Or Adjuvant Androgen Deprivation Therapy For Rp
Neoadjuvant or adjuvant ADT with RP may have benefits in some patients with local or locally advanced PCa, where there is evidence that this approach provides a significant survival advantage . The European Association of Urology guidelines recommend that adjuvant ADT be offered upon detection of nodal involvement during RP .
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Salvage Androgen Deprivation Therapy
Recurrence following RP can potentially be managed with salvage ADT, although data supporting this use is generally obtained from retrospective studies . Not all patients with BCR after primary curative treatment benefit from salvage ADT however, a favourable effect is observed in a high-risk group, which may be defined as having a short PSA-DT and/or by tumour characteristics . Factors that may favour ADT after RP include a very high risk of clinical recurrence, good recovery of continence, long life expectancy, and the patient being anxious about the future or not being ready to accept the idea of sRT.
The National Cancer Institute of Canada PR-7 trial compared intermittent with continuous ADT in men with BCR and no evidence of metastatic disease after definitive or salvage RT and RP. OS in the intermittent arm was not inferior to that in the continuous arm, and intermittent therapy was associated with beneficial effects on certain domains of QoL. Salvage ADT for BCR may therefore be most appropriately delivered in an intermittent fashion, with the possible exception of patients with a Gleason score of 8 or higher .
What Factors Increase The Chance Of Cancer Recurrence
The likelihood of metastasis occurring increases with higher grade and stage of the cancer as the more aggressive and developed the cancer is, the higher the chance of it breaking out of the prostate. More specifically:
- High Gleason grades
- High clinical stages
- Positive surgical margins .
However, most prostate cancers are cured with surgery. As an example, using my results from operations performed on over 2,300 men with a variety of stages and grades, 96.3% of operations resulted in full cancer cure. Some combinations of minor prostate cancer had a 100% cancer cure rate, but the higher you go, the lower the full cancer cure rate.
The commonest sites of recurrence of prostate cancer following surgery are:
- the prostate bed 80% of recurrence cases
- lymph nodes 15% of cases
- bones 5% of cases.
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Recurrence Of Prostate Cancer Life Expectancy
According to the table above, when the prostate cancer recurrence rate is low, then life expectancy generally is 10 years or higher. When calculating life expectancy to a prostate expectancy too.
Meanwhile, if the recurrence rate is high, then most probably the tumor will involve the adjacent areas. And often the recurrence seems to occur after 6-8 years of radical prostatectomy.
In cases of metastastasis, it is difficult to assess the period of relapse. This is actually considered as very high risk zone.
Sometimes, the actual cause is not the prostate cancer, but some other associated problems. That’s why, it is highly recommended regular annual check-ups not only to tackle prostate cancer, but also a scheduled check-up to detect its recurrence and related problems too.
When Does It Happen
Median time to BCR ranges from 20 to 38 months . Although BCR occurs more often in first 3 years from RP, longer follow-ups are required whereas a considerable number of patients may recur even after 15 years . In a retrospective survey of RP performed from 1982 to 1999 with a median follow-up of 5.9 years, overall BCR rates in 5, 10 and 15 years were 16%, 28% and 39%, respectively . More recently, in a series comprising almost 2.500 patients submitted to RP followed longer than 10 years, authors found BCR rates of 34.3%, 44% and 52.7% at 10, 15 and 20 years after RP, respectively. Relative risk of BCR following surgery decreased with time, but late PSA increase was not negligible, as BCR rates rose by 18.4% from 10 to 20 years .
Many clinical and pathological variables have been shown to indicate the likelihood of BCR after RP. A single variable is not enough to predict biochemical failure. These variables should be graded into nomograms for accurately predicting BCR. In the most studied nomograms CAPRA-S and Stephensons nomogram, main variables significantly associated with BCR were preoperative PSA and primary and secondary Gleason grades, followed by seminal vesicle invasion , positive surgical margins , extraprostatic extension and lymph node involvement .
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