Currently, radical prostatectomy or radical radiotherapy is considered the standard treatment for clinically limited prostate cancer, and biochemical recurrence of prostate cancer specifically occurs after radical prostatectomy or radiation therapy. PSA monitoring is an important indicator of biochemical recurrence, and the detection and proper evaluation of biochemical recurrence during follow-up can screen high-risk patients for further treatment, thereby improving their quality of life.
Proper evaluation can screen high-risk patients for further treatment, thus improving the quality of life of patients.
I. Diagnosis of biochemical relapse
Biochemical relapse, also known as PSA relapse, is biochemical relapse after radical surgery and biochemical relapse after radiotherapy.
(A) Biochemical recurrence after radical surgery
After successful radical prostate cancer surgery, the patient’s serum prostate-specific antigen (PSA) level should drop to a value of 0 within 24 weeks and remain at this clinically undetectable level. Currently, the range PSA 0.2 ng/ml-0.6 ng/ml that defines biochemical recurrence, which exact value is currently controversial. The European Association of Urology (EAU) defines serum PSA levels ≥0.2 ng/ml twice in a row as biochemical relapse; while Am et al. believe that the definition is limited to PSA ≥0.4 ng/ml twice in a row.
(B) Biochemical recurrence after radiotherapy
The American Society for Therapeutic Radiology and Oncology (ASTRO) defines it as an increase in serum PSA ≥2 ng/ml or when the patient receives another radical treatment. Most scholars now define biochemical relapse after radiotherapy as three consecutive serum PSA increases after the nadir of serum PSA values after radical radiotherapy, with the exact time of relapse being the midpoint moment between the nadir of serum PSA and the first increase.
II. Assessment of biochemical recurrence
In patients with biochemical recurrence of prostate cancer, the purpose of further comprehensive evaluation is to determine whether the patient has experienced clinical recurrence, and if clinical recurrence has occurred, it is extremely important to determine whether it is local recurrence or metastasis, as this directly affects the choice of treatment options. in an analysis of the literature related to PSA doubling time (PSADT) after 2000, Maffezzini et al. obtained that PSADT is one of the most effective indicators to evaluate the prognosis of prostate cancer after radical treatment.
The likelihood of local recurrence after radical surgery is greater than 80% when: PSA rise is detected only 3 years after surgery; PSADT ≥ 11 months: Gleason score ≤ 6; pathological stage ≤ pT3. The likelihood of metastasis after radical surgery was greater than 80% when: PSA rise was detected within 1 year after surgery; PSADT ≥ 4 two months; Gleason score ≤ 8-10; pathological stage ≤ pT3b. D’Amico obtained in an analysis of 8669 patients after radical treatment of prostate cancer that PSADT, PSA growth rate, and Gleason score are ~guidelines for the assessment of biochemical recurrence of prostate cancer. PSADT <3 months, PSA growth rate >2ng/ml per year, and Gleason score ≥8 are called prostate cancer.specific mortality.PCSM.
Clinical recurrence after radiotherapy also includes local recurrence and/or metastasis. Local recurrence refers to prostate cancer recurrence after radiotherapy confirmed by prostate puncture when lymph node or distant metastasis is ruled out by CT, MRI, bone scan and other imaging examinations. Distant metastasis refers to the evidence of distant dissemination found by imaging.
III. Treatment of biochemical recurrence
After proper evaluation of patients with biochemical recurrence, different treatments are chosen for different patients. The available treatments are watchful waiting, salvage radiotherapy, endocrine therapy, etc. If the possibility of local recurrence is high, watchful waiting or salvage radiotherapy can be chosen; if the possibility of extensive metastasis is high, endocrine therapy should be chosen; if the clinical local recurrence is clear, salvage radiotherapy should be chosen; if the clinical metastasis is clear, endocrine therapy should be chosen.
(I) Watchful waiting treatment
Indications: Indicated for low-risk patients with an initial small increase in PSA, Gleason score ≤7, biochemical recurrence 2 years after radical surgery and biochemical recurrence with PSADT >10 months (because such patients have very slow disease progression with a median time from bullous recurrence to clinical recurrence or metastasis of 8 years and a median time from the occurrence of metastasis to death of 5 years). Contraindications: (1) biochemical recurrence with a high probability that distant metastases will occur, PSA rise within one year after surgery: PSADT at 4-6 months: Gleason score at 8-10: pathological stage ≥ T3b; (2) clinically extensive metastases.
(II) Salvage radiotherapy
Indications: (1) Life expectancy >l 0 years;
(2) good general physical condition;
(3) Patients at high risk of biochemical recurrence;
(4) Local recurrence in the clinical prostate fossa. Local recurrence should be treated with salvage radiotherapy targeting the prostate bed at serum PSA levels ≤1.5 ng/ml at a total dose of 64-66 Gy. Milecki et al. showed that radiotherapy and androgen blockade for patients at high risk of biochemical recurrence (T>3, Gleason score 8.10, preoperative PSA>20 ng/m1) therapy improves patients’ first-chance survival time 1.H] and quality of bovine life and is recommended.Nguyen et al. reported that for patients with preoperative PSA <10 ng/ml, Gleason score ≤6, and clinical stage of T. or T:. Stage, preoperative PSA growth rate <2.0 ng/ml, postoperative biochemical recurrence at >3 years and >12 months, negative bone scan, and positive repeat biopsy in low-risk patients was found to significantly improve survival time.Freedland et al. conducted a|uI-considerative study of 7,000 prostate cancer patients and found that in these patients with biochemical recurrence, for small I Division risk patients who chose a non-indolent remedial treatment, the median survival from biochemical recurrence after radical surgery or radiotherapy to death was 16 years, the sooner, the worse the prognosis. For low-risk patients, the choice of salvage radiotherapy is able to improve patient survival, for high-risk patients, it is better to choose endocrine therapy. moul et al. in the treatment after postgraduate chemotherapy relapse pointed out that successful salvage radiotherapy depends on the dose of radiotherapy and the value of PSA, the general dose of radiotherapy is at least 66-70Gy and PSA is 0.5-2ng/ ml, but of course there is also individual variability.
Contraindications: (1) Life expectancy
(C) Endocrine therapy
Indications: (1) Patients with biochemical recurrence and a high propensity for clinically extensive metastasis, with rising PSA occurring within one year after surgery; PSAD at 4-6 months; Gleason score of 8-10; pathological stage ≥ T3b: (2) Local recurrence in the clinical prostate fossa, but who cannot tolerate radiotherapy or are unwilling to undergo radiotherapy: (3) PSA >20ng/ml before radical surgery, a Gleason score >7, positive extensive surgical margins or tumor with extraperitoneal invasion, endocrine therapy should be performed as early as possible. For early or delayed endocrine therapy after biochemical recurrence. The UK Medical Research Council study showed that early endocrine therapy after biochemical recurrence is better than delayed endocrine therapy.
Modalities of endocrine therapy.
(1) Denervation therapy surgical removal of both testes. It results in a rapid and sustained decrease in testosterone to very low levels and is the main method of denervation, with the main adverse effect being the psychological impact on the patient. Pharmacological depot is the use of luteinizing hormone-releasing hormone analogues (LHRH-a, such as leuprolide, treprostinil, etc.), and testosterone gradually F drops after one week to reach depot levels at 3-4 weeks.
(2) maximal androgen blockade (MAB) depot plus anti-androgen drugs to remove or block both testicular-derived and adrenal-derived androgens. Denervation combined with the non-steroidal anti-androgen flutamide and nilumet improved the 5-year survival rate in 2.9% of patients.
(3) Intermittent endocrine therapy (IHT) has been reported in 50 patients with biochemical recurrence of prostate cancer after radical prostatectomy, and after 9 months of starting intermittent endocrine therapy when PSA rose above 3.0 ng/ml, all patients’ PSA fell below 0.5 ng/ml or reached the value of 0. After 9 months of intermittent endocrine therapy, all patients’ PSA dropped below 0.5 ng/ml or reached 0, at which point treatment was stopped, and treatment was started again after the patient’s PSA rose again to 3.0 ng/ml. However, there is not enough evidence to support this treatment as routine treatment for patients with biochemical recurrence.
(4) Antiandrogen monotherapy and combined anti-androgen and 5-alphareductase inhibitor therapies. These approaches have proven effective in in vitro tumor cell line experiments and animal studies, but there is a lack of information on clinical trial studies. These methods have less adverse effects and can also preserve the patient’s sexual function, so they have some prospect of application in young patients with biochemical recurrence.
(iv) Salvage radical surgery
It is mainly adapted to patients with biochemical relapse after radical radiotherapy, and the selection of patients requires life expectancy >lO years, clinical stage ≤T curvature stage at the time of relapse, biopsy Gleason score <7, PSA <10 ng,nll before radiotherapy, and PSA <4ng imperial before salvage surgery. It is generally believed that the longer the interval between the first treatment and biochemical recurrence, the better the therapeutic effect. The method has been difficult to be recognized at the beginning due to many surgical complications, the main complications are rectal injury, bladder neck contracture, bleeding, ureteral injury, vesicorectal fistula, deep vein embolism, fat embolism, etc. w1. Due to fibrosis, adhesions and occlusion of tissue planes caused by radiotherapy, salvage radical prostate cancer treatment is difficult, and there is no unified opinion on whether the surgery should be performed with pelvic lymph node dissection, but a number of scholars advocate that it should be performed routinely.