Localized prostate cancer (prostate cancer) - Surgery

Active surveillance of patients with localized prostate cancer involves regular, thorough examination and determination of the PSA level (for example, once every 3 months) without any treatment until symptoms of the disease occur or the PSA value exceeds a certain level.

Conservative treatment of prostate cancer (prostate gland cancer) is generally adequate only for patients over 70 years of age, with limited (T1a) stage of the disease and expected life expectancy of less than 10 years. This form of the disease is often detected after TUR for prostate adenoma. In this case, prostate cancer will progress in only 10-25% of patients within 10 years, it rarely develops into a widespread form within 5 years. In patients with highly differentiated prostate cancer, the tumor, as a rule, grows and spreads quite slowly, for most elderly men there is no need for treatment under active surveillance.

Some retrospective studies with a follow-up period of 5-10 years question the need for radical treatment of patients with stage T1.

However, many arguments argue against the use of watchful waiting in early stage prostate cancer. Aus et al. found that of a group of patients with non-metastatic prostate cancer who survived for more than 10 years, 63% ultimately died of the disease. There is no doubt that patients with clinical stage T2 prostate cancer who are treated conservatively have a high risk of developing metastases and dying from the disease.

The data presented confirm the opinions of many specialists about the advisability of the tactics of active observation of patients in the group of patients with a life expectancy of less than 10 years. At present, there is no doubt that patients with clinical stage T2 prostate cancer who are observed or receive conservative treatment have a high risk of developing metastases and death from this disease.

Thus, the policy of active surveillance is controversial and is often rejected by doctors.

Currently, the most realistic alternatives to active surveillance tactics for localized forms of prostate cancer are radical prostatectomy and radiation therapy.

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Radical prostatectomy

Radical prostatectomy (RP) is the main method of treating patients with localized forms of prostate cancer. Indications for its implementation:

• localized forms of cancer (T1-2);
• life expectancy over 10 years;
• no contraindications to anesthesia.

There are two types of surgical approaches used to perform radical prostatectomy: retropubic and perineal. Both surgical techniques are similar in terms of radicality, subsequent survival, and the frequency of positive surgical margins. Some authors report a slightly higher frequency of positive apical surgical margins with the retropubic approach, as opposed to a more frequent anterior positive surgical margin with the perineal approach; however, it is unclear what clinical significance this fact has.

The advantages and disadvantages of each of the described approaches have been discussed many times. One of the main advantages of the perineal approach is the absence of contact with the abdominal cavity, which reduces the risk of postoperative intestinal obstruction, reduces postoperative pain and the duration of hospitalization; the main disadvantages are the possibility of damage to the rectum, difficulty in visualizing the vascular-nerve bundles, and sometimes difficulties in dissection of the seminal vesicles. The advantages of the retropubic approach are the possibility of bilateral pelvic lymphadenectomy, as well as preservation of all vascular-nerve bundles and potency. The main disadvantage is the need for an abdominal incision, which increases the duration of hospitalization. The final choice is individual, it also depends on the preferences of the urologist (based on his experience).

One of the most common complications of radical prostatectomy, occurring in 30-100% of cases, is erectile dysfunction, which depends on the patient's age and the surgical technique (nerve-sparing or not). Another common complication is urinary incontinence, which occurs in 2-18% of patients after surgery (in 27.5% in a mild form). The problem of impotence and urinary incontinence is partially solved by some surgical techniques: preservation of the longer distal end of the urethra, the bladder neck and vascular-nerve bundles. The use of intraurethral and intracorporeal administration of prostaglandins, as well as phosphodiesterase-5 inhibitors, are quite effective methods for treating impotence after radical prostatectomy.

As mentioned earlier, it is quite common for the pathological stage to be higher than the clinical stage after radical prostatectomy, occurring in 30-40% of patients. In such patients, the tumor usually progresses much faster. Moreover, in a study of 7,500 patients, the incidence of positive surgical margins was found to be 14 to 41%. In patients with positive surgical margins and undetectable PSA levels, subsequent adjuvant treatment is probably necessary.

In conclusion, radical prostatectomy is undoubtedly an effective treatment for patients with localized prostate cancer, despite the fact that it is accompanied by some loss in quality of life.

Endoscopic radical prostatectomy

Laparoscopic radical prostatectomy was first performed by WW Schuessler in 1990. French urologists presented an improved surgical technique. A Raboe in 1997 developed extraperitoneal endoscopic radical prostatectomy, and Bollens R. (2001) and Stolzenburg JU (2002) modified and improved it. The advantages of endoscopic prostatectomy are low invasiveness, precision, lower blood loss, short hospitalization and rehabilitation period. The disadvantages of this technique include the need for specialized equipment and instruments, and a long training period for urologists.

Indications for endoscopic radical prostatectomy are the same as for retropubic prostatectomy, namely locally advanced prostate cancer in patients with an expected life expectancy of at least 10 years. Contraindications for it, as for other laparoscopic operations, are disorders of the blood coagulation system and pronounced changes in the function of external respiration and cardiac activity, general infectious diseases, purulent-inflammatory processes on the anterior abdominal wall. Relative contraindications include excess body weight, small and large prostate volume (less than 20 cm ² and more than 80 cm ⁵ ), neoadjuvant treatment, previous prostate surgeries (TUR, transvesical or retropubic adenomectomy). These factors complicate the isolation of the prostate and contribute to the occurrence of intraoperative complications.

At present, there are no long-term oncological results of laparoscopic and endoscopic prostatectomy. However, preliminary results indicate equal oncological effectiveness of open and laparoscopic prostatectomy. Positive surgical margins are detected depending on the stage of the disease in 11-50%. Overall and adjusted 5-year survival is 98.6 and 99.1%, 3-year relapse-free - 90.5%.

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Alternative treatment for prostate cancer

The search for effective and safe methods of treating prostate cancer has remained one of the most pressing issues in urology in the last decade. The most common modern minimally invasive methods of treating localized prostate cancer are brachytherapy, cryoablation, and high-frequency focused ultrasound.

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Cryoablation

Cryoablation is the destruction of prostate tissue by freezing. This is achieved by destroying cell membranes with ice crystals, dehydrating tissues, and disrupting microcirculation due to hypothermia. In existing systems, this is ensured by argon circulation in needles inserted into the glandular tissue. At the same time, it is necessary to heat the urethra to prevent its necrosis using a special catheter. The process is controlled by several sensors. The temperature in the glandular tissue decreases to -40 °C. Cryoablation is applicable to patients with localized forms of prostate cancer, the prostate volume limit is 40 cm ³, with a larger gland volume it can be covered by the pelvic bones, as with perineal brachytherapy. Preliminary hormonal treatment is possible to reduce the prostate volume. At the dawn of the first generation of systems for cryotherapy of prostate cancer, enthusiasm was aroused by the simplicity of the method, the absence of the need for tissue irradiation, low trauma and good tolerability. However, as experience accumulated, negative aspects of the method were discovered - a high risk of damage to the rectal wall with the formation of fistulas, impotence, difficulty in controlling the border of the "ice ball" zone around the probe, urinary incontinence. Great hopes are associated with the so-called third generation of cryosurgery units, which use argon to cool tissues and helium to heat them. They have a complex tissue temperature control system with several temperature sensors in the bladder neck and external sphincter area and visualization using rectal ultrasound in real time.

Indication for cryoablation is localized prostate cancer, especially in patients who are not interested in maintaining potency or who do not have it at the time of treatment initiation. Cryoablation can be performed in patients with small tumors that invade the capsule if there is a chance of getting the extraprostatic part of the tumor into the freezing zone. A gland volume of more than 50 cm3 ^can complicate the procedure due to the problem of one-stage adequate freezing of a large volume of tissue and interference from the pubic symphysis. In such cases, preliminary hormonal treatment to reduce the prostate volume is possible.
Evaluation of effectiveness depends on the success criteria used and the patient's risk group. With a PSA threshold of 0.5 ng/ml and 1 ng/ml, the 5-year relapse-free period in the low-risk group (PSA less than 10, Gleason sum less than 6, stage less than T2a) reaches 60 and 76%, respectively.

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Highly focused ultrasound

Highly focused ultrasound also has a place in the treatment of localized prostate cancer.

In addition to primary cancer treatment, highly focused ultrasound is used as a salvage therapy for local relapses after external beam radiation therapy. The method involves the action of ultrasound waves on tissues, the increase in temperature of which leads to their lethal damage, the appearance of a necrotic focus. The final effect is achieved due to the disruption of lipid membranes and protein denaturation, as well as mechanical disruption of the normal tissue structure during the formation of gas bubbles and cavitation. The last two points create a technical problem of very precise energy dosing, since they make it difficult to clearly predict the boundaries of the necrotic focus. Its volume is small, so it is necessary to repeat the procedure several times to treat large areas of tissue. In existing devices, ultrasound is used both for tissue destruction and for visualization; the rectal head combines two crystals with different frequencies or one crystal with a variable frequency. During the procedure, it is important to constantly monitor the position of the rectal wall to avoid damage. The use of neoadjuvant hormonal treatment or TUR of the prostate before the procedure is possible to reduce its volume. The size is limited to 60 cm2 ^. It is also possible to conduct two consecutive sessions, since after the first the prostate size decreases. Highly focused ultrasound is a minimally invasive and safe procedure that does not require long-term hospitalization. As a rule, a urethral catheter is left for several days after the procedure.

Possible, although rare, complications include urethral-rectal fistula (1%), postoperative urinary retention is common among patients who have not undergone prior TUR of the prostate, catheterization or epicystostomy may be necessary. Impotence occurs in every second patient. Urinary incontinence may be a consequence of thermal damage to the external sphincter and occurs to varying degrees in 12% of patients.

Success criteria are negative control biopsy, decrease in PSA level to the threshold value of 0.6 ng/ml (achieved 3 months after the procedure) and absence of dynamics of its growth during subsequent observation. At the moment, there is insufficient data to evaluate remote results. However, for patients with low risk according to control biopsy data 6 months after treatment, a negative result occurs in 87% of observations. In general, the technique is already widely used in many European countries, and as experience accumulates, it finds its place in the treatment of prostate cancer.

Adjuvant treatment of prostate cancer (prostate cancer)

Adjuvant treatment of prostate cancer (prostate cancer) had a significant effect on the recurrence rate and mortality in patients with localized breast cancer. Extrapolation of such results to patients with prostate cancer is important in patients with positive surgical margins or PSA levels below the nadir. Adjuvant treatment is also suggested to be effective in patients with limited disease, positive surgical margins, preoperative PSA levels above 10 ng/mL, and a Gleason score of 7 or more. Possible options include antiandrogen monotherapy, luteinizing hormone-releasing hormone (LHRH) analogs, and possibly finasteride. Adjuvant treatment with orchiectomy and radiotherapy in patients with stage T3N0M0 disease who underwent radical prostatectomy resulted in local and systemic progression of the process, with no significant change in survival. A large, placebo-controlled trial of 8,000 patients is currently nearing completion evaluating the use of bicalutamide (150 mg/day) as monotherapy after radical prostatectomy or radiotherapy in patients with limited prostate cancer. The primary endpoints of the trial are survival, time to progression, and cost per life-year gained.

There are currently results from studies of adjuvant treatment in patients with locally advanced disease after radiotherapy. A recent study conducted by the European Organization for Research and Treatment of Bladder Cancer, involving 415 patients with locally advanced cancer, showed that the use of depot goserelin immediately before and for 3 years after radiotherapy significantly improves local control and survival after 45 months of follow-up. Five-year survival rates estimated by Kaplan Meier are 79 and 62%, respectively, for the adjuvant arm of the study and the arm of patients who received radiotherapy alone (follow-up period of 5 years). Adjuvant treatment is also effective for large tumors after radiotherapy (study conducted by RTOG using depot goserelin).

Thus, adjuvant hormonal therapy is a promising treatment method that is currently undergoing detailed testing. Survival rates are objectively better after radiation therapy, use after radical prostatectomy requires further study. The main criteria for using hormonal adjuvant treatment are effectiveness, good tolerability, maintaining quality of life at a sufficient level (especially sexual function), convenient administration and dosing regimen.

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Conclusions

The stage of the tumor process, the patient's age and somatic status are of great importance in determining the tactics of treatment of localized prostate cancer. In patients with localized prostate cancer, the life expectancy after treatment does not differ from that in the population. Such positive results are the result of a number of factors:

• favorable latent course of cancer (in particular diagnosed with
• identification and effective treatment of aggressive forms of the disease;
• rational use of hormonal treatment to prevent relapse.

With the advent of population screening with PSA testing, the question of whether we are actually diagnosing clinically significant prostate cancer and whether we should perform radical prostatectomy on all such patients must be answered - the available information suggests that the majority of malignancies diagnosed are clinically significant. However, screening is controversial; the American Cancer Society guidelines recommend PSA screening in men over 50 years of age, while informing about its potential risks and benefits. In the United States, a reduction in prostate cancer incidence and mortality can be associated with screening (PSA + digital rectal examination). Therefore, there is an urgent need for additional randomized controlled trials on this issue.

Currently, numerous studies have been conducted on the effectiveness of alternative treatments for patients with prostate cancer (radical prostatectomy, external beam radiation therapy, active surveillance with delayed hormonal therapy).

For some patients, the potential benefit of therapy is small. Therefore, treatment alternatives largely depend on the patient's choice. Further analysis shows that for a specific group of patients (younger patients and those with highly differentiated prostate cancer), radical prostatectomy or radiotherapy are the treatment of choice. Active surveillance is an appropriate alternative for most people, especially those with poor somatic status. However, the accuracy of treatment choice also depends on the impact on the patient's quality of life, and further research is needed in this area.

The cost-effectiveness calculation is also important, and must be done in terms of “gained” years of life. Radical prostatectomy, so popular in many countries, is a relatively expensive treatment alternative. In the US, its cost is twice as high as radiation therapy ($18,140 versus $9,800). According to insurance companies, about 60,000-70,000 radical prostatectomies are performed annually, and their cost is high. The treatment of complications is also taken into account.

In general, no one can predict the tumor's tendency to progress, so most doctors tend to perform active surgical treatment, especially in patients under 75 years of age and with an expected life expectancy of more than 10 years. Time will tell whether this is justified or not.

On the other hand, in patients with a life expectancy of less than 10 years, hormonal therapy and watchful waiting should be considered as an alternative. Antiandrogens are playing an increasingly important role in the treatment of early stages of the disease, and ongoing studies will confirm or refute this position. When treating with antiandrogens, the urologist should pay attention to such conditions as tolerability and dosing regimen to achieve compliance. Neoadjuvant treatment before radiotherapy is also justified, but before surgery, its routine use is limited by the lack of adequate information. Such methods as high-frequency interstitial radioablation of the tumor and high-intensity focused ultrasound are also undergoing preliminary trials. Cryotherapy, photodynamically enhanced laser treatment and brachytherapy are of interest. However, further studies of these alternatives are needed.

Further research in this area addresses the role of growth factors, oncogenes, tumor suppressor genes, and apoptosis inducers.

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