(A) Follow-up after curative treatment of prostate cancer
Curative treatment of prostate cancer refers to radical prostatectomy and radiation therapy, including external irradiation or brachytherapy, or a combination of these treatments.
1. Indicators of follow-up after curative treatment.
(1), changes in serum PSA level: monitoring the changes in serum PSA level is the basic content of the follow-up of prostate cancer.
1. Monitoring of PSA after radical prostatectomy: PSA should not be detectable three weeks after successful radical prostatectomy. persistent elevation of PSA indicates the presence of PSA-producing tissue in the body, i.e. residual prostate cancer lesions. After radical prostatectomy, two consecutive serum PSA levels above 0.2 ng/ml suggest biochemical recurrence of prostate cancer [212-214].
Because there is a clearance period for PSA, the first PSA test after radical prostatectomy should be performed between 6 weeks and 3 months postoperatively and should be repeated when an elevated PSA is found to rule out errors in laboratory tests. A value between 0.2 and 0.4 ng/ml may be the most appropriate criterion for biochemical recurrence, and choosing a lower value may improve the sensitivity of detecting clinical recurrence, but a higher value can improve specificity. If two consecutive serum PSA levels ≥0.4ng/ml are defined as biochemical relapse, this criterion correlates best with clinical progression.
2. monitoring of PSA after radiotherapy: the gland remains after radiotherapy and PSA levels decline slowly [215]. The lowest PSA value after radiotherapy is a marker of biochemical cure and an important prognostic factor. In general, the lower the value the higher the cure rate, and it is generally accepted that those with a minimum PSA level of 1 ng/m1 within 3-5 years have a better prognosis, and 80% of 10-year survivors after radiotherapy have PSA levels below lng/ml [216-218]. Regardless of whether endocrine therapy was applied concomitantly, PSA levels were considered to have biochemical recurrence when they were elevated above the PSA nadir of 2 ng/mL or more than 2 ng/mL after radiotherapy, and the time of biochemical recurrence was the time when this occurred. This criterion has higher sensitivity and specificity for predicting clinical recurrence compared with the older criteria for biochemical recurrence after radiotherapy and is a good predictor of distant metastases, etiology-specific mortality, and overall mortality [219-221].
Previous criteria for biochemical recurrence after radiotherapy required retrospective biochemical recurrence times, resulting in artifacts of early decline and late flattening of the Kaplan-Meier curve, and it was not closely related to clinical prognosis. Since there is a natural increase in PSA levels after the recovery of androgen secretion, the previous criteria would cause an increase in pseudo-biochemical relapse in these patients and would not explain the common PSA rebound in radiotherapy patients [9-11]. Biochemical relapse is only a definition and does not imply the need to start remedial therapy; the application of adjuvant or remedial therapy should be individualized according to the overall risk factors of the patient and needs to be judged based on a combination of benefits and risks of treatment.
Studies suggest that PSA kinetics may be an important prognostic determinant. A PSA doubling time (PSA doublingtime, PSADT) shorter than 3 months after radical prostatectomy and radiation therapy is strongly associated with prostate cancer-specific mortality, and remedial endocrine therapy may be considered for such patients. For patients with internal irradiation, patients with PSA doubling time shorter than 12 months may require aggressive remedial therapy [223].
(2), rectal examination (DRE): DRE is used to determine the presence of local recurrence of prostate cancer, and local recurrence should be suspected if there are new nodules in the prostate area after curative treatment. Routine DRE is not necessary after radical prostatectomy and radical radiation therapy, but only regular serum PSA testing is required to determine whether there is recurrence. If the serum PSA is elevated further investigations including DRE are needed. tumors with Gleason score 8~10 sometimes do not secrete PSA, such patients should routinely undergo DRE, in addition, DRE should also be performed for patients with tumors that do not secrete PSA.
(3), transrectal ultrasound and biopsy: The purpose of the examination is to detect histological evidence of local recurrence, and prostate biopsy is not used as a routine follow-up. After radiation therapy, prostate biopsy is not recommended when remedial prostatectomy and other treatments are not being considered. If biopsy is needed, it should be performed after 18 months of radiation therapy [226]. The positive prostate biopsy rate is 54% in those with biochemical recurrence and 78% in those with abnormal DRE [227-229]. Prostatic fossa biopsy is recommended after radical surgery if PSA is greater than 0.5 ng/m1, if local nodules are found on DRE, or if local hypoechoic lesions are found on transrectal ultrasonography [229].
(4), bone scan with abdominal CT/MRI and PET/CT scan: biochemical recurrence does not mean local recurrence, and some patients may have distant metastases, and sensitive imaging methods are needed to detect local and distant lesions for further salvage local treatment. Negative biopsies do not exclude local recurrence, and positive biopsies do not exclude metastases; the significance of biopsies remains uncertain [20]. The aim of these tests is to detect metastases in prostate cancer and is not recommended as a routine follow-up in patients without symptoms and without evidence of biochemical recurrence.The role of MRI and PET/CT scans in the detection of recurrent prostate cancer lesions is increasingly appreciated [230-233].MRI, especially dynamic-enhanced MRI, is able to detect early in patients with PSA < 2 ng/ml local recurrent lesions and helps to select patients for prostate biopsy and to improve sensitivity, narrow the scope of radiotherapy, and improve treatment tolerance.PET/CT scans are able to detect local and distant metastases, and 11C-choline PET/CT scans have the best sensitivity. Patients with skeletal symptoms can undergo bone scans without having to consider serum PSA levels. Bone scan can be used for those with PSA levels greater than 20 ng/m1, PSADT less than 6 months, or PSA rates greater than 0.5 ng/m1/month [234-235].
2. follow-up protocols.
(1), after curative treatment is the beginning of follow-up. The first follow-up visit mainly examines treatment-related complications, such as the presence of urinary incontinence, bowel symptoms, and sexual function status. The follow-up method can be modified according to the characteristics of the tumor or patient. For example, patients with highly differentiated prostate cancer that is confined to the envelope or within the surgical specimen should be followed more closely for patients with low-differentiated, locally progressive tumors or those with positive surgical margins than those with highly differentiated prostate cancer.
(2) For monitoring of asymptomatic patients: clinical manifestations related to prostate cancer, detection of serum PSA level or and DRE are the routine follow-up methods. Follow-up should be performed every 3 months within the first 2 years after treatment, every 6 months after 2 years, and annually after 5 years. It is necessary to shorten the follow-up interval.
(B) Follow-up after endocrine therapy for prostate cancer
The purpose of follow-up is to clarify the role of further treatment according to the different stages of the disease in order to avoid useless tests and excessive financial burden. On the other hand, if the disease progresses, an effective treatment plan can be given, so a strict follow-up program must be defined.
1.Follow-up items after endocrine therapy
(1) PSA examination: the sensitivity of endocrine therapy and the duration of response are judged according to the pre-treatment PSA level and the decrease in PSA level during the initial 3-6 months of treatment [236]. The prognostic value of pre-treatment PSA levels for determining prognosis is controversial in the literature and therefore cannot be used to predict the duration of response to endocrine therapy [237].
PSA levels at 3 and 6 months after endocrine therapy are associated with prognosis. Lower PSA levels at 3 and 6 months after treatment may be associated with a longer duration of responsiveness to treatment. However diseased individuals differ and this criterion does not have absolute value [238].
Patients should be monitored regularly in the early stages of endocrine therapy. Regular PSA monitoring in asymptomatic patients allows earlier detection of biochemical recurrence, as elevated PSA levels usually precede clinical symptoms by several months. However, it must be emphasized that PSA levels are not a reliable marker of escape and should not be used as a follow-up test alone. Clinical progression occurs in approximately 15-34% of patients whose PSA levels may be normal [239].
(2) Monitoring of creatinine, hemoglobin, and liver function: monitoring creatinine is valuable in progressive tumors because it can detect upper urinary tract obstruction. Monitoring of hemoglobin and liver function can also indicate disease progression and toxicity of endocrine therapy. The latter often leads to discontinuation of therapy (e.g., hepatotoxicity of non-steroidal anti-androgen drugs) [240].
Alkaline phosphatase and its bone-specific isoenzymes can be used to monitor patients in stage M1b. Compared to PSA, these markers have the advantage of being independent of the direct effects of endocrine therapy. Endocrine therapy can elevate serum alkaline phosphatase, in which case bone-specific alkaline phosphatase may be helpful [241].
(3) Bone scan, ultrasound and chest radiograph: asymptomatic patients with normal PSA do not require a bone scan [242]. A bone scan should be performed in those with elevated PSA and bone pain during endocrine therapy. Ultrasound and chest radiographs should be performed if necessary.
(4) Serum testosterone level monitoring: it has been reported in the literature that the application of LHRH analogues in a few patients cannot bring down the blood testosterone to the surgical trend level. Therefore, regular blood testosterone level monitoring is necessary for patients who receive drug trend.
(5) Monitoring of metabolic complications: De-androgenization therapy can cause a series of corresponding complications due to a significant reduction in blood testosterone levels, including: hot flashes, loss of libido, erectile dysfunction, gynecomastia, and loss of bone mineral density. In addition, lower blood testosterone levels can lead to an increased incidence of insulin resistance, arterial stiffness, diabetes mellitus and metabolic syndrome.
Therefore, it is recommended that patients older than 65 years with a previous history of cardiovascular disease should be evaluated by a cardiovascular physician before receiving androgen therapy; all patients should be screened for diabetes at the beginning of and every three months after receiving androgen therapy, and suspected patients should undergo a glucose tolerance test and, if necessary, be seen by an endocrinologist; all patients receiving androgen therapy should receive lifestyle and behavioral counseling, such as diet, food and drink, and a diet and a diet. All patients receiving deandrogen therapy should be given lifestyle and behavioral guidance, such as diet, exercise, and smoking cessation.
2. Timing of follow-up It is recommended that an initial follow-up assessment be performed every 3rd and 6th month after the start of endocrine therapy. For stage M0 patients with good response to treatment, such as improvement in symptoms, good psychological status, good compliance with treatment, and PSA level less than 4ng/ml, follow-up visits can be conducted every 6 months. For stage M1 patients with good response to treatment, if symptoms improve, psychological status is good, treatment compliance is good, and PSA level is less than 4ng/ml, follow-up can be done every 3-6 months. When the disease progresses, the follow-up interval should be shortened, because it is beneficial to stop the anti-androgen therapy at this time. For patients who are resistant to endocrine therapy, disease progression occurs and they do not respond to standard treatment, an individualized follow-up program is feasible.