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Recurrence of prostate cancer after radical treatment
Last reviewed: 23.04.2024
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The risk of recurrence of prostate cancer (local or systemic) within 10 years after prostatectomy or radiation therapy is 27-53%. Within 5 years after the initial treatment, 16 to 35% of patients receive anti-relapse treatment.
Earlier, a relapse was understood as a tumor, palpable through the rectum, as well as distant metastases. The relapse is considered to be the growth of the PSA level. The criterion for relapse after prostatectomy is usually considered to be a PSA level of 0.2 ng / ml or more in two consecutive measurements. Relapse after radiation therapy, according to ASTRO criteria, can be said with three consecutive increases in PSA.
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Local and systemic relapse of prostate cancer
If an increase in the level of PSA is found, it is important to establish the nature of relapse - local or systemic. After prostatectomy, there may be a local relapse, in other cases only a systemic relapse or a combination thereof.
Distinguishing local relapse from systemic helps time to increase PSA levels, growth rate and time of doubling of PSA content, its baseline and Gleason index.
An increase in PSA in the first half of the year after surgery usually indicates a systemic relapse. The median time of doubling the level of PSA in systemic relapses can be 4.3, at local - 11.7 months. The rate of increase in the level of PSA less than 0.75 ng / ml per year is observed in patients with local relapses, more than 0.7 ng / ml per year - in patients with distant metastases.
On local relapse after radiation therapy indicates a slow delayed increase in the level of PSA. Confirmation of local recurrence is a positive result of a biopsy performed in 18 months. After irradiation and later (in the absence of distant metastases according to CT, MRI and scintigraphy data).
The probability of local recurrence after prostatectomy is 80% with late rise in PSA level (more than 3 years), time of PSA doubling more than 11 months, Gleason index less than 6 and process stages below pT 3a N 0 and pT x R 1 Probability of systemic recurrence after prostatectomy exceeds 80% with an early rise in the level of PSA (less than one year), the time of doubling the level of PSA 4-6 months, the Gleason index of 8-10, the stages of pT 3b and pT x N 1. Local relapse after radiotherapy and HIFU is diagnosed with a positive biopsy result in the absence of distant metastases. A biopsy of the prostate gland is only shown to individual patients in the planning of repeated local treatment (eg, prostatectomy or a re-session of HIFU).
Examination for suspected recurrence of prostate cancer
To confirm a relapse with an increase in PSA levels, a physical examination, ultrasound, CT or MRI of the pelvis, a biopsy of the tumor bed and an anastomosis area are usually performed. In the absence of symptoms, these studies rarely show a tumor, as the increase in PSA levels usually occurs 6-48 months before the apparent relapse.
Finger rectal examination at zero or very low PSA levels usually does not work. With an increase in the level of PSA, MRI of the small pelvis, CT of the abdominal cavity and bone scintigraphy are prescribed, but because of low sensitivity and specificity for early relapse, these studies are poorly informative. With the rise in PSA after prostatectomy, the result of scintigraphy is positive only in 4.1% of patients. The probability of a positive scintigraphy result does not exceed 5%, until the PSA level reaches 40 ng / ml. The average PSA level at which scintigraphy detects metastases should exceed 60 ng / ml, and the rate of PSA increase is 22 ng / ml per year. The level and rate of increase in PSA content allow predicting the result of scintigraphy, and the rate of PSA growth is the result of CT. Thus, with a PSA level of less than 20 ng / ml or a PSA increase rate of less than 20 ng / ml per year, scintigraphy and CT do not bring additional information. Endorectal MRI reveals a local recurrence in 81% of patients with an average PSA level of 2 ng / ml.
PET is recommended for early diagnosis of recurrence of various tumors.
Scintigraphy with antibodies to the prostatic membrane antigen (prostoscintis) is one of the new methods of detecting relapses. Its diagnostic accuracy reaches 81%. Regardless of the level of PSA, the method reveals the occurrence of relapse in 60-80% of patients, which can help in choosing the tactics of treatment. Scintigraphy with these antibodies is positive in 72 of 255 patients with a PSA level of 0.1-4 ng / ml after prostatectomy, and isotope accumulation is observed at any level of PSA.
Biopsy of the anastomosis zone allows relapse only in 54% of patients. Only in the presence of a palpable or hypoechoic formation, the probability of a positive result is close to 80%. There is a clear correlation between this indicator and PSA level: with a PSA content of less than 0.5 ng / ml, the result is positive in 28% of patients, with a PSA level of more than 2 ng / ml in 70% of patients. Given these data, biopsy from the anastomosis zone is usually not take and are guided by the level of PSA and the rate of its doubling. In addition, survival with proven relapses is about the same as when recording an isolated increase in PSA.
According to ASTRO recommendations, with an increase in PSA levels after radiation therapy, biopsy of the prostate gland is not indicated. However, a biopsy is of key importance in resolving the issue of prostatectomy or HIFU in such patients. After radiotherapy (remote or brachytherapy), the biopsy is usually performed no earlier than 18 months after cryodestruction or 6 months after ultrasound destruction.
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Treatment of recurrence of prostate cancer
Treatment of recurrence of prostate cancer after radical prostatectomy
The timing and tactics of treatment with a rise in PSA levels after prostatectomy or radiation therapy cause discussion. In case of relapse after the operation, observation is possible, irradiation of the tumor bed, HIFU-therapy for relapse, hormone therapy for prostate cancer (including combined, periodic or combined use of finasteride and antiandrogens), and a combination of hormone and chemotherapy. These methods are also applicable for relapse after radiation therapy.
Hormonotherapy
At a high preoperative level of PSA (more than 20 ng / m, Gleason index more than 7, non-radical surgery and locally advanced tumors pT 3b, pT x N 1 ) early hormonotherapy is suitable. However, its effect on survival has not yet been established. With early hormone therapy, metastases are less common than with delayed, survival in both cases is approximately the same. The need for hormone therapy confirms the trial of MRS, in which relapse was noted in all patients receiving radiation therapy for the increase in PSA level after prostatectomy for tumors of pT 3b, pT x N 1, and Gleason index 8.
Monotherapy with antiandrogenic drugs patients are better tolerated than combined (less frequent tides, decreased potency, loss of sexual desire), but antiandrogens cause gynecomastia and pain in the nipples. In patients without distant metastases, bicalutamide (150 mg / day) significantly reduces the risk of disease progression. Thus, antiandrogens can be an alternative to castration with an increase in PSA levels after radical treatment (especially in relatively young patients without concomitant diseases).
Observation for relapse of prostate cancer
Dynamic observation is usually performed at Gleason index less than 7, late (2 years after surgery) increase in PSA level and the time of its doubling more than 10 months. In such cases, the median time to the onset of metastases is 8 years, and the median time from the onset of metastases to the onset of death is another 5 years.
HIFU-therapy
Recently, more and more data on the results of HIFU-therapy of local recurrence after RP have appeared. Most often, a relapse is detected with a TRUS and is confirmed histologically (biopsy). Nevertheless, HIFU-therapy pouring postpone the timing of the appointment of hormone therapy. Accurate data on survival are absent.
Clinical recommendations for treatment of relapse after prostatectomy
With local relapse and a PSA level of less than 1.5 ng / ml, radiotherapy up to 64-66 Gy,
If the patient is weakened or objected to irradiation, local relapse may result in a dynamic observation
With the growth of the level of PSA, indicating a systemic relapse, hormone therapy is shown, as it reduces the risk of metastasis.
As hormone therapy, analogues of gonadoliberin, castration or bicalutamide (150 mg / day) can be used.
Treatment of relapse after radiation therapy
Most patients with relapse after radiation therapy receive hormone therapy (up to 92%). Without treatment, the time from the increase in PSA to the manifestation of relapse is about 3 years. In addition to hormone therapy in case of relapse after irradiation, local treatment is possible - prostatectomy, HIFU-therapy, cryotherapy, brachytherapy. Prostatectomy was not widely used due to frequent complications (urinary incontinence, rectal damage), and also because of the high risk of local recurrence. However, with careful selection of patients, this operation can provide a long period without relapse,
According to the latest data. 5-year recurrence-free survival after radiation therapy corresponds to that after primary prostatectomy performed at the same stages of the disease, a 10-year survival rate of 60-66%. Within 10 years from the progression of the tumor, 25-30% of patients die. With localized tumors, the absence of tumor cells at the margin of resection, invasion of seminal vesicles, and metastasis to the lymph nodes, disease-free survival is 70-80% compared to 40-60% for locally advanced tumors.
Prostatectomy with local recurrence is justified in the absence of severe co-morbidities, an expected LIFE of at least 10 years, Gleason index tumors less than 7, and a PSA level of less than 10 ng / ml. In other cases before the operation it is difficult to determine the prevalence of the tumor, which increases the risk of anterior or total exenteration, complications, and also repeated relapse.
Dynamic monitoring of patients with a probable local recurrence (from a low-risk group, with a late relapse and a slow increase in the PSA level), are set up against repeated radical treatment. Retrospective analysis did not reveal the advantages of hormone therapy compared with dynamic observation at the time of doubling the PSA level for more than 12 months; 5-year survival without metastasis was 88% for hormone therapy and 92% for the background of observation.
Clinical recommendations for a survey for suspected recurrence of prostate cancer
After prostatectomy, if the PSA level is less than 20 ng / ml and the rate of its growth is less than 20 ng / ml per year, CT of the abdominal cavity and small pelvis is of little informative.
Endorectal MRI helps detect local relapse with a low PSA level (1-2 ng / ml). PET has not yet become widespread.
Scintigraphy with labeled antibodies to the prostatic membrane antigen allows detection of recurrence in 60-80% of patients regardless of the level of PSA.
A biopsy to confirm local relapse is performed after 18 months or more after irradiation.
[6], [7], [8], [9], [10], [11]
Clinical recommendations for treatment of relapse after radiation therapy
In some patients with local recurrence, prostatectomy is possible.
With contraindications to surgery, brachytherapy, HIFU therapy or cryodestruction may be performed.
With a possible systemic recurrence, hormone therapy for prostate cancer is possible.
Clinical recommendations for the treatment of relapses after radical treatment
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Probable local recurrence after prostatectomy |
It is possible radiotherapy in a dose of at least 64 Gy, it is desirable to start it at a PSA level of less than 1.5 ng / ml. |
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Probable local recurrence after radiation therapy |
In some cases, prostatectomy is possible, but the patient should be informed of the relatively high risk of complications. |
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Probable systemic relapse |
Early hormone therapy slows progression and may increase survival compared to delayed. Local treatment is carried out only for palliative purposes. |