(A) Symptoms of prostate cancer
Early prostate cancer is usually asymptomatic, but when the tumor invades or obstructs the urethra or bladder neck, symptoms similar to lower urinary tract obstruction or irritation may occur, and in severe cases, acute urinary retention, hematuria and urinary incontinence may occur. Bone metastasis will cause bone pain, pathological fracture, anemia, spinal cord compression leading to lower limb paralysis, etc.
(II) Diagnosis of prostate cancer
Most patients with prostate cancer can be clinically diagnosed histopathologically through systematic puncture biopsy of the prostate. However, the initial suspicion of prostate cancer is usually determined by rectal examination of the prostate or serum prostate-specific antigen (PSA) examination before prostate biopsy is performed. Rectal examination combined with PSA is currently recognized as the best primary screening method for early detection of prostate cancer [1].
1. digital rectal examination (DRE) Most prostate cancers originate in the peripheral zone of the prostate, and DRE is valuable for the early diagnosis and staging of prostate cancer [2-3]. Considering that DRE may affect PSA values, DRE should be performed after PSA blood sampling.
2. prostate-specific antigen (PSA) test PSA as a single test has a higher positive diagnostic prediction rate of prostate cancer compared with DRE and TRUS (transrectal ultrasonography), and it can also improve the diagnosis rate of limited prostate cancer and It can also improve the diagnosis of limited prostate cancer and increase the chance of radical prostate cancer treatment.
(1) Timing of PSA screening: The American Urological Association (AUA) and the American Society of Clinical Oncology (ASCO) recommend that men over the age of 50 should undergo routine DRE, PSA screening annually. For the population of men with a family history of prostate cancer, annual screening should be performed starting at age 45 [4-6]. A consensus of experts in Taiwan, China, implemented the US recommendations [7].
In China, a consensus was reached by expert discussion that routine PSA and DRE examinations should be performed in men over 50 years of age with lower urinary tract symptoms, and for the male population with a family history of prostate cancer, regular examinations and follow-up should begin at age 45. PSA should be performed on men with abnormal DRE, clinical signs (such as bone pain, fractures, etc.) or imaging abnormalities, etc.
PSA test should be performed 1 week after prostate massage, 48 hours after rectal examination, cystoscopy, catheterization and other operations, 24 hours after ejaculation and 1 month after prostate puncture. PSA test should be performed without acute prostatitis, urinary retention and other diseases.
(2) Determination of PSA results: The current consensus at home and abroad is that a total serum PSA (tPSA) >4.0ng/ml is abnormal. A repeat test is recommended for those with initial PSA abnormalities. When tPSA is between 4~10ng/ml, the possibility of prostate cancer is more than 25% (information from Europe and America). The incidence of prostate cancer in Chinese is low, and a domestic data set showed that the positive rate of prostate cancer puncture was 15.9% when the serum total PSA was 4~10ng/ml [8]. Serum PSA is influenced by factors such as age and prostate size, and the age-specific tPSA values for each age group of patients with prostate hyperplasia (BPH) in China were 0-1.5ng/ml for 40-49 years, 0-3.0ng/ml for 50-59 years, 0-4.5ng/ml for 60-69 years, 0-5.5ng/ml for 70-79 years, and ≥80 years for 0 to 8.0ng/ml [9]. This constitutes the gray area for performing prostate cancer determination, and the following PSA-related variables should be referenced within this gray area.
(3) Free PSA (fPSA): fPSA and tPSA are routinely tested simultaneously. Most studies have shown that fPSA is an effective method to improve the detection rate of prostate cancer with tPSA levels in the gray zone.
When serum tPSA is between 4 and 10 ng/ml, fPSA levels are negatively correlated with the incidence of prostate cancer. Studies have shown that if a patient’s tPSA is in the above range and fPSA/tPSA is <0.1, the likelihood of prostate cancer in that patient is as high as 56%; conversely, if fPSA/tPSA is >0.25, the likelihood of prostate cancer is only 8%. In China, fPSA/tPSA > 0.16 is recommended as a normal reference value (or critical value) [10-18].
(4) PSA density (PSA density, PSAD for short): the ratio of total serum PSA value to prostate volume. PSAD is calculated by rectal ultrasound measurement. the normal value of PSAD is <0.15. PSAD helps to differentiate prostate hyperplasia from prostate cancer. When a patient's PSA is at the high limit of normal or mildly elevated, the PSAD can be used to guide the physician in deciding whether to perform a biopsy or follow-up [19-22]. the PSAD can be used as one of the clinical reference indicators.
(5) PSA velocity (PSA velocity, PSAV for short): that is, the change of serum PSA level is continuously observed, and the PSAV of prostate cancer is significantly higher than that of prostate hyperplasia and normal people. Its normal value is <0.75ng/ml/year. If PSAV is >0.75ng/ml/year, prostate cancer should be suspected [23-24]. PSAV is more suitable for young patients with low PSA values. PSA should be tested at least 3 times within 2 years: PSAV calculation formula: [(PSA2-PSA1) + (PSA3- PSA2)]/2
3. transrectal ultrasonography (TRUS) Under TRUS guidance in the prostate as well as in the surrounding tissue structures, suspicious lesions are sought and the volume size of the tumor can be initially determined [25]. However, TRUS has low specificity for the diagnosis of prostate cancer, and the detection of a hypoechoic prostate lesion has to be differentiated from normal prostate, BPH, PIN, acute or chronic prostatitis, prostate infarction and prostate atrophy. Systematic puncture biopsy of the prostate under TRUS guidance is the main method for prostate cancer diagnosis.
4.Prostate puncture biopsy Systematic puncture biopsy of the prostate is the most reliable test to diagnose prostate cancer.
(1) Timing of prostate puncture: Because the bleeding of prostate puncture affects the clinical staging of imaging. Therefore, prostate puncture biopsy should be performed after MRI and under the guidance of ultrasound and others [26-29].
(2) Indications for prostate puncture
1) Rectal examination reveals nodules with any PSA value.
2) Ultrasound finding of hypoechoic nodules in the prostate or MRI finding of abnormal signal, any PSA value.
3) PSA >10ng/ml, any f/t PSA and PSAD values.
4) PSA 4~10ng/ml, abnormal f/t PSA or abnormal PSAD value.
Note: PSA 4~10ng/ml, if f/t PSA, PSAD values and imaging are normal, should be followed closely.
(3) Number of prostate puncture needles: Systematic puncture biopsy is recognized by most physicians. The results of the study showed that the diagnostic positivity rate of more than 10 punctures was significantly higher than that of less than 10 punctures, and did not significantly increase complications [30-31].
(4) Repeat puncture: a negative result of the first prostate puncture requires repeat puncture in the following 1) to 4) cases [32-34].
1) First puncture pathology reveals atypical hyperplasia or high-grade PIN.
2) PSA >10ng/ml, any f/t PSA or PSAD.
3) PSA 4~10ng/ml with abnormal retest f/t PSA or PSAD values, or abnormal rectal finger examination or imaging.
4) PSA 4~10ng/ml, recheck f/t PSA, PSAD, rectal exam and imaging are normal. Follow up closely and recheck PSA every 3 months. if PSA > 10ng/ml for 2 consecutive times or PSAV > 0.75/ml/year, re-puncture should be performed.
5) Timing of repeat punctures: The interval between 2 punctures is still controversial, but currently it is mostly 1~3 months.
6) Number of repeat punctures: For 2 negative puncture results, more than 2 punctures are recommended for those who belong to the above-mentioned cases 1) to 4).
7) If 2 punctures are negative and there are severe urinary symptoms caused by prostatic hyperplasia, transurethral resection of the prostate is feasible and the specimen will be sent to pathology for systematic biopsy.
5.Other imaging tests for prostate cancer
(1) Computed tomography (CT) examination: CT is less sensitive than magnetic resonance imaging (MRI) for the diagnosis of early prostate cancer, and the purpose of CT examination for prostate cancer patients is mainly to assist clinicians in clinical staging of the tumor [35]. For invasion of tumor adjacent tissues and organs and metastatic lymph node enlargement in the pelvis, the diagnostic sensitivity of CT is similar to that of MRI.
(2) Magnetic resonance (MRI/MRS) scan: MRI examination can show the integrity of the prostate envelope, whether it invades the surrounding prostate tissues and organs, and MRI can also show the invasion of pelvic lymph nodes and the foci of bone metastases. It has a more important role in clinical staging [36]. Magnetic resonance spectroscopy (MRS) presents different spectral lines based on the differences in the metabolism of citrate, choline and creatinine in prostate cancer tissues compared with those in prostate hyperplasia and normal tissues, and has some value in the diagnosis of prostate cancer.
MRI examination is often unable to make a definitive diagnosis when differentiating prostate cancer from lesions such as prostatitis with calcification, larger benign prostatic hyperplasia, prostate scarring, and tuberculosis [36]. Therefore, TRUS, CT, MRI and other imaging examinations have limitations in the diagnosis of prostate cancer, and the final definitive diagnosis requires prostate puncture biopsy to obtain a histological diagnosis.
(3) Nuclear examination (ECT) of prostate cancer: the most common distant metastatic site of prostate cancer is the bone. eCT can detect bone metastases 3 ~ 6 months earlier than conventional X-ray, with higher sensitivity but lower specificity [37].
Once the diagnosis of prostate cancer is established, whole-body bone imaging is recommended [38] (especially in cases with PSA >20 and GS score >7), which can help determine the accurate clinical stage of prostate cancer.
6. pathological grading In terms of pathological grading of prostate cancer, the Gleason scoring system is recommended [39]. Prostate cancer tissues are divided into major grading zones and minor grading zones, and the Gleason score of each zone is 1~5. The Gleason score is the sum of the Gleason scores of major grading zones and minor grading zones to form the cancer tissue grading constant.
Grading criteria.
Gleason 1: Carcinoma is extremely rare. Its boundary is very clear, swelling type growth, almost no invasion of stroma, cancerous glandular vesicles are very simple, mostly round, moderate size, closely arranged together, and its cytoplasm is extremely similar to benign epithelial cell cytoplasm.
Gleason 2: Carcinomas are rare and mostly occur in the metastatic area of the prostate. The boundaries of the carcinomas are not very clear, and the carcinoma vesicles are separated by the stroma, are simple and round, may vary in size, may be irregular, and are loosely arranged together.
Gleason 3: The most common cancer is found in the peripheral zone of the prostate. The most important feature is the infiltrative growth, the cancerous glandular vesicles are of different sizes and shapes, the nuclei are large and red, and the cytoplasm is mostly alkaline stained.
Gleason 4: Poorly differentiated, infiltrative growth with irregularly fused cancerous vesicles forming tiny papillae or sieves with large, red nucleoli and alkaline or gray staining cytoplasm.
Gleason 5: Poorly differentiated carcinoma with regular round or irregular border, with infiltrative growth, lamellar single cell type or pimple-like carcinoma type with necrosis, large nuclei, large and red nucleoli, and variable cytoplasmic staining.