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Globally, radical prostatectomy is a recognized treatment for prostate cancer
.
In high-risk patients (ie Gleason score>(4 + 3) = 7 [ISUP grade>3], or clinical stage T3-4, or prostate specific antigen (PSA)> 20ng/ml), more doctors Will choose radiotherapy + androgen deprivation therapy (ADT) instead of surgery to avoid the toxicity caused by the use of triple therapy (surgery + radiotherapy + ADT)
.
Among the selective population after radical prostatectomy, the most commonly used regimen is radiotherapy + ADT salvage treatment
.
NCCN, AUA, and EAU guidelines all recommend that for patients whose PSA rises after surgery, salvage radiotherapy, salvage radiotherapy ± ADT or observation should be considered
.
However, none of the guidelines clearly pointed out the best plan for specific populations
.
The 2021 edition of the NCCN guidelines pointed out that for patients with persistent or increased PSA after prostatectomy and no evidence of metastasis, it is recommended to consider salvage radiotherapy ± ADT
.
The EAU guidelines point out that there is strong evidence for active monitoring and delayed rescue radiotherapy, while evidence for immediate rescue ADT is limited
.
The AUA guidelines point out that due to the lack of high-quality evidence, there is no recommendation for the best radiation therapy strategy
.
It is worth noting that none of the above guidelines point out specific recommendations for imaging imaging when biochemical recurrence or specific PSA values
.
However, it is pointed out that traditional CT and bone scans are less sensitive to identify metastasis and local recurrence (PSA level <1 ng/ml), while the evidence for other imaging methods (such as PET) is limited
.
This article takes into account the various factors of salvage treatment for patients with biochemical recurrence after radical prostatectomy, and discusses the influencing factors when choosing salvage treatment options
.
Figure Considerations and key points of treatment options for patients with recurrence after radical prostatectomy The clinical markers of local and distant recurrence after radical prostatectomy include PSA levels, dynamics, pathological features, genomic risk scores, and imaging findings
.
During the consultation after prostatectomy, clinicians should evaluate PSA level, PSA doubling time, biochemical failure interval (PSA>0.
2ng/ml), patient comorbidities, urination disorders, urinary control function, erectile function, and appearance over time Symptoms, medications, and genomic risks (if possible)
.
CT and bone scans are inaccurate when PSA <5ng/ml, so they should be avoided at this time
.
The ideal observation objects are: elderly (age>80 years old), low Gleason score (6-7 points [ISUP grade 1-2]), long PSA doubling time (>12-18 months), and biochemical failure time Long interval (> 5-10 years), low absolute value of PSA at relapse (<0.
5ng/ml), multiple complications, high risk of death due to competing causes, no distant metastasis on imaging
.
Patients with high-risk characteristics may be suitable candidates for salvage radiotherapy
.
ADT should be considered for patients with PSA>0.
5ng/ml
.
Although patients with other high-risk features (which may indicate occult metastatic disease) may also benefit from ADT, it is possible that only patients with confirmed metastasis should receive ADT
.
Management of elevated PSA after radical prostatectomy and other factors to be considered All patients after prostatectomy should be tested for PSA level; usually, PSA<0.
05ng/ml is undetectable
.
Patients with undetectable PSA are not suitable for postoperative definitive radiotherapy.
In the years after treatment, PSA can be routinely tested and may fluctuate (usually within 2 ng/ml)
.
If PSA can be detected after prostatectomy, there is reason to suspect distant metastasis
.
When multiple values are available, the PSA doubling time is more useful
.
The short PSA doubling time (<12-18 months) means that it may be aggressive and disseminated
.
If PSA rises to >0.
2ng/ml, the time interval for biochemical failure can be calculated
.
The short interval between biochemical failures (<6-12 months) means that there is a high possibility of invasion or spread of disease
.
The patient’s complications should be evaluated, especially as it may cause other problems (such as heart disease and stroke) and face the risk of death
.
Patients should be evaluated for urinary dysfunction, urinary control function, and erectile function
.
Radiotherapy should be avoided until urinary control is stable
.
After surgery, pelvic floor muscle exercises (usually called Kegel exercises) should be encouraged
.
The use of drugs should be recorded
.
Certain drugs may lower PSA, such as statins, aspirin, hydrochlorothiazide, and 5-alpha reductase inhibitors
.
If possible, the genomic risk of disease recurrence should be assessed
.
CT and bone scan imaging are not accurate when PSA is less than 5ng/ml and should be avoided
.
When PSA <0.
5ng/ml, sodium fluoride PET-CT is not accurate and should be avoided
.
Patients with elevated PSA after radical resection and with the following characteristics should consider observing elderly patients (>80 years old)
.
Compared with young people, the elderly may be more likely to die from competitive risk factors
.
Gleason score is low (6-7 points [ISUP grade 1-2])
.
PSA doubling time is long (12-18 months)
.
The interval between biochemical failures is long (5-10 years)
.
There are complications
.
The absolute value of PSA is low at relapse (<0.
5 ng/ml)
.
Imaging shows no distant metastasis
.
In fact, you should try to get the most accurate imaging results
.
It is difficult to make treatment decisions based on bone scan and CT results alone
.
Remarks: The more the above features, the more suitable the patient is for observation
.
The following features suggest that patients with elevated postoperative PSA should receive salvage radiotherapy for younger patients (age <70 years)
.
Compared with the elderly, it takes longer for younger patients to develop metastatic disease and die from the risk of prostate cancer
.
Gleason score is low (<8 points [ISUP rating <4])
.
PSA doubling time is long (>12~18 months)
.
The surgical margin was positive
.
For example, if the patient has a positive resection margin and a slow rise in PSA, it is likely to be a local recurrence rather than a distant metastasis
.
The initial PSA after surgery was undetectable
.
There are fewer complications
.
The risk of dying from competitive risk factors is low
.
The absolute value of PSA before salvage radiotherapy is low (<0.
5 ng/ml)
.
Consider adding ADT when PSA>0.
5 ng/ml
.
The target area of salvage radiotherapy can cover the metastatic site
.
Increasing selective pelvic lymph node radiotherapy is expected to improve the prognosis of patients with biochemical recurrence, but it cannot improve overall survival
.
Radiotherapy to the pelvic lymph nodes can increase toxicity
.
Therefore, the use of selective nodular radiotherapy is generally discouraged
.
Imaging shows no distant metastasis
.
In fact, you should try to get the most accurate imaging results
.
It is difficult to make treatment decisions based on bone scan and CT results alone
.
Remarks: The more the above characteristics, the more suitable the patient to receive salvage radiotherapy
.
Patients with increased PSA after radical prostatectomy and with the following characteristics should be considered for patients with disease metastases who receive intermittent ADT imaging confirmation (eg, CT, bone scan, PET-CT)
.
Especially patients with extensive metastasis (non-oligometastasis)
.
This is the main consideration when using ADT
.
For patients with oligometastatic disease, stereotactic radiotherapy can be considered for metastatic tumors
.
The surgical margin was negative
.
For example, if the patient has a negative surgical margin and a rapid increase in PSA, it is more likely to be a distant metastasis rather than a local recurrence
.
The biochemical failure interval is short (<1 year)
.
The absolute value of PSA is high at recurrence (>5-10 ng/ml)
.
PSA doubling time is short (<6~12 months)
.
Gleason score is high (> 8 points [ISUP rating> 4])
.
Remarks: The more the above characteristics, the more suitable for ADT treatment
.
References: Zaorsky NG, Calais J, Fanti S, Tilki D, Dorff T, Spratt DE, Kishan AU.
Salvage therapy for prostate cancer after radical prostatectomy.
Nat Rev Urol.
2021 Nov;18(11):643-668.
doi : 10.
1038/s41585-021-00497-7.
Epub 2021 Aug 6.
PMID: 34363040.
.
In high-risk patients (ie Gleason score>(4 + 3) = 7 [ISUP grade>3], or clinical stage T3-4, or prostate specific antigen (PSA)> 20ng/ml), more doctors Will choose radiotherapy + androgen deprivation therapy (ADT) instead of surgery to avoid the toxicity caused by the use of triple therapy (surgery + radiotherapy + ADT)
.
Among the selective population after radical prostatectomy, the most commonly used regimen is radiotherapy + ADT salvage treatment
.
NCCN, AUA, and EAU guidelines all recommend that for patients whose PSA rises after surgery, salvage radiotherapy, salvage radiotherapy ± ADT or observation should be considered
.
However, none of the guidelines clearly pointed out the best plan for specific populations
.
The 2021 edition of the NCCN guidelines pointed out that for patients with persistent or increased PSA after prostatectomy and no evidence of metastasis, it is recommended to consider salvage radiotherapy ± ADT
.
The EAU guidelines point out that there is strong evidence for active monitoring and delayed rescue radiotherapy, while evidence for immediate rescue ADT is limited
.
The AUA guidelines point out that due to the lack of high-quality evidence, there is no recommendation for the best radiation therapy strategy
.
It is worth noting that none of the above guidelines point out specific recommendations for imaging imaging when biochemical recurrence or specific PSA values
.
However, it is pointed out that traditional CT and bone scans are less sensitive to identify metastasis and local recurrence (PSA level <1 ng/ml), while the evidence for other imaging methods (such as PET) is limited
.
This article takes into account the various factors of salvage treatment for patients with biochemical recurrence after radical prostatectomy, and discusses the influencing factors when choosing salvage treatment options
.
Figure Considerations and key points of treatment options for patients with recurrence after radical prostatectomy The clinical markers of local and distant recurrence after radical prostatectomy include PSA levels, dynamics, pathological features, genomic risk scores, and imaging findings
.
During the consultation after prostatectomy, clinicians should evaluate PSA level, PSA doubling time, biochemical failure interval (PSA>0.
2ng/ml), patient comorbidities, urination disorders, urinary control function, erectile function, and appearance over time Symptoms, medications, and genomic risks (if possible)
.
CT and bone scans are inaccurate when PSA <5ng/ml, so they should be avoided at this time
.
The ideal observation objects are: elderly (age>80 years old), low Gleason score (6-7 points [ISUP grade 1-2]), long PSA doubling time (>12-18 months), and biochemical failure time Long interval (> 5-10 years), low absolute value of PSA at relapse (<0.
5ng/ml), multiple complications, high risk of death due to competing causes, no distant metastasis on imaging
.
Patients with high-risk characteristics may be suitable candidates for salvage radiotherapy
.
ADT should be considered for patients with PSA>0.
5ng/ml
.
Although patients with other high-risk features (which may indicate occult metastatic disease) may also benefit from ADT, it is possible that only patients with confirmed metastasis should receive ADT
.
Management of elevated PSA after radical prostatectomy and other factors to be considered All patients after prostatectomy should be tested for PSA level; usually, PSA<0.
05ng/ml is undetectable
.
Patients with undetectable PSA are not suitable for postoperative definitive radiotherapy.
In the years after treatment, PSA can be routinely tested and may fluctuate (usually within 2 ng/ml)
.
If PSA can be detected after prostatectomy, there is reason to suspect distant metastasis
.
When multiple values are available, the PSA doubling time is more useful
.
The short PSA doubling time (<12-18 months) means that it may be aggressive and disseminated
.
If PSA rises to >0.
2ng/ml, the time interval for biochemical failure can be calculated
.
The short interval between biochemical failures (<6-12 months) means that there is a high possibility of invasion or spread of disease
.
The patient’s complications should be evaluated, especially as it may cause other problems (such as heart disease and stroke) and face the risk of death
.
Patients should be evaluated for urinary dysfunction, urinary control function, and erectile function
.
Radiotherapy should be avoided until urinary control is stable
.
After surgery, pelvic floor muscle exercises (usually called Kegel exercises) should be encouraged
.
The use of drugs should be recorded
.
Certain drugs may lower PSA, such as statins, aspirin, hydrochlorothiazide, and 5-alpha reductase inhibitors
.
If possible, the genomic risk of disease recurrence should be assessed
.
CT and bone scan imaging are not accurate when PSA is less than 5ng/ml and should be avoided
.
When PSA <0.
5ng/ml, sodium fluoride PET-CT is not accurate and should be avoided
.
Patients with elevated PSA after radical resection and with the following characteristics should consider observing elderly patients (>80 years old)
.
Compared with young people, the elderly may be more likely to die from competitive risk factors
.
Gleason score is low (6-7 points [ISUP grade 1-2])
.
PSA doubling time is long (12-18 months)
.
The interval between biochemical failures is long (5-10 years)
.
There are complications
.
The absolute value of PSA is low at relapse (<0.
5 ng/ml)
.
Imaging shows no distant metastasis
.
In fact, you should try to get the most accurate imaging results
.
It is difficult to make treatment decisions based on bone scan and CT results alone
.
Remarks: The more the above features, the more suitable the patient is for observation
.
The following features suggest that patients with elevated postoperative PSA should receive salvage radiotherapy for younger patients (age <70 years)
.
Compared with the elderly, it takes longer for younger patients to develop metastatic disease and die from the risk of prostate cancer
.
Gleason score is low (<8 points [ISUP rating <4])
.
PSA doubling time is long (>12~18 months)
.
The surgical margin was positive
.
For example, if the patient has a positive resection margin and a slow rise in PSA, it is likely to be a local recurrence rather than a distant metastasis
.
The initial PSA after surgery was undetectable
.
There are fewer complications
.
The risk of dying from competitive risk factors is low
.
The absolute value of PSA before salvage radiotherapy is low (<0.
5 ng/ml)
.
Consider adding ADT when PSA>0.
5 ng/ml
.
The target area of salvage radiotherapy can cover the metastatic site
.
Increasing selective pelvic lymph node radiotherapy is expected to improve the prognosis of patients with biochemical recurrence, but it cannot improve overall survival
.
Radiotherapy to the pelvic lymph nodes can increase toxicity
.
Therefore, the use of selective nodular radiotherapy is generally discouraged
.
Imaging shows no distant metastasis
.
In fact, you should try to get the most accurate imaging results
.
It is difficult to make treatment decisions based on bone scan and CT results alone
.
Remarks: The more the above characteristics, the more suitable the patient to receive salvage radiotherapy
.
Patients with increased PSA after radical prostatectomy and with the following characteristics should be considered for patients with disease metastases who receive intermittent ADT imaging confirmation (eg, CT, bone scan, PET-CT)
.
Especially patients with extensive metastasis (non-oligometastasis)
.
This is the main consideration when using ADT
.
For patients with oligometastatic disease, stereotactic radiotherapy can be considered for metastatic tumors
.
The surgical margin was negative
.
For example, if the patient has a negative surgical margin and a rapid increase in PSA, it is more likely to be a distant metastasis rather than a local recurrence
.
The biochemical failure interval is short (<1 year)
.
The absolute value of PSA is high at recurrence (>5-10 ng/ml)
.
PSA doubling time is short (<6~12 months)
.
Gleason score is high (> 8 points [ISUP rating> 4])
.
Remarks: The more the above characteristics, the more suitable for ADT treatment
.
References: Zaorsky NG, Calais J, Fanti S, Tilki D, Dorff T, Spratt DE, Kishan AU.
Salvage therapy for prostate cancer after radical prostatectomy.
Nat Rev Urol.
2021 Nov;18(11):643-668.
doi : 10.
1038/s41585-021-00497-7.
Epub 2021 Aug 6.
PMID: 34363040.
