Locally advanced prostate cancer: treatment

Locally advanced cancer of the prostate cancer (T3), which extends beyond the capsule of the prostate with invasion of paresis prostatic tissue, bladder neck, seminal vesicles, but without lymph node involvement or distant metastases.

Numerous studies show that the results of treatment of patients with locally advanced prostate cancer are inferior to those in the group of patients with localized risk. Nevertheless, the imperfection of methods of staging prostate cancer at this stage of diagnosis leads to an overestimation of the clinical stage of the disease, more often - to its underestimation.

Speaking about patients with prostate cancer in stage T3, it must be remembered that they represent a fairly diverse group, different in terms of pathological criteria, which seriously affects the choice of treatment and life expectancy. To date, the optimal method for this category of patients has not yet been determined.

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Locally advanced prostate cancer: operations

According to the guidance of the European Association of Urology, prostate resection in patients with locally advanced prostate cancer is considered possible (PSA less than 20 ng ml, stage T3a: G equal to 8 or less). At the same time, a number of specialists showed that surgery (as myo-therapy) is most effective in the group of patients with stage T3a with a PSA level of less than 10 ng / ml. So in 60% of patients for 5 years there were no recurrences of the disease, and the overall survival for 6-8 months of observation was 97.6%.

Performing a resection of the prostate in patients with a PSA of less than 20 ng / ml and G equal to 8 or less can be beneficial, but the likelihood of using adjuvant treatment (hormonal, radiation) is extremely high.

Surgical treatment of patients with stage T3a includes the removal of the prostate with enlarged lymphodissection, thorough apical dissection, complete removal of seminal vesicles, resection of the neurovascular bundles and the neck of the bladder.

The frequency of postoperative complications in prostate resection in patients with prostate cancer T3, such as impotence, urinary incontinence, is higher than in the operative treatment of localized forms.

For patients with a well, moderately and poorly differentiated tumor (pT3), cancer-specific survival for 10 years is 73, 67 and 29%, respectively. The attitude towards neoadjuvant treatment is ambiguous. Despite the fact that its use reduces the frequency of positive surgical margins by 50%, the survival time of patients in this group does not differ significantly from those to whom only surgical treatment was performed. Studies are carried out on the effectiveness of a combination of chemotherapy drugs as a neoadjuvant treatment, and also to increase its duration to 9-12 months.

The use of adjuvant (hormonal, chemo- or radiotherapy) therapy, especially in the group of high-risk patients (G is equal to 8 or less), the stage with T3a can significantly improve the results of treatment. According to recent studies, 56-78% of patients with prostate cancer in stage T3a need adjuvant treatment after resection of the prostate; while the 5 and 10-year carcinospecific survival was 95-98 and 90-91%, respectively.

Indications for adjuvant treatment:

• extended surgical margin;
• detected metastases in the lymph nodes;
• high-risk group (G is 8 or less);
• invasion of the tumor into seminal vesicles.

Currently, there are works in which resection of the prostate in combination with adjuvant therapy is considered as an alternative to non-invasive multimodal treatment (combination of radiotherapy and hormonal therapy) in patients in stage T3a.

Thus, resection of the prostate is an effective method of treating patients with locally advanced prostate cancer. The best candidates for resection of the prostate are patients who have an overestimated stage of the local process, an unextended extracapsular extension, highly moderately differentiated tumors. PSA is less than 10 ng / ml.

In young patients, a low-grade tumor or germination into seminal vesicles can not be contraindications to resection of the prostate.

Locally advanced prostate cancer cancer: other treatments

Radiotherapy is the preferred method of treating patients with locally advanced prostate cancer. At the same time, many specialists propose a multimodal approach, i.e. Combination of radiation and hormonal treatment.

Thus, a balanced approach is needed to treat patients with prostate cancer in stage T3a. The doctor must compare criteria such as patient's age, survey data, indications for choosing a particular treatment method for possible complications, only after that, taking into account the wishes of the patient himself and his informed consent to begin treatment.

Radiation therapy of prostate cancer

Remote radiation therapy for prostate cancer involves the use of y-irradiation (usually photons) directed at the prostate and surrounding tissues through multiple irradiation fields. To minimize radiation damage to the bladder and rectum, three-dimensional conformal radiation therapy has developed, in which the irradiation fields are focused on the prostate. The most effective form of three-dimensional conformal radiation therapy is modulation of the intensity of irradiation. Radiation therapy with intensity modulation provides localization of irradiation in geometrically complex fields. Modulation of the intensity of irradiation is possible on a linear accelerator equipped with a modern multilobal collimator and a special program: the movement of the collimator flaps uniformly distributes the dose in the irradiation field, creating concave isodose curves. Radiation therapy with heavy particles carried out by high-energy protons or neutrons is also used to treat prostate cancer.

Indications for radiation therapy: localized and locally advanced prostate cancer. Palliative therapy is used for bone metastases, compression of the spinal cord, metastases in the brain. Radionuclide treatment of Str is used for palliative treatment of hormone-refractory prostate cancer.

Contraindications to radiation therapy: the general severe condition of the patient, cancer cachexia, severe cystitis and pyelonephritis, chronic retention of urination, chronic renal failure. Relative contraindications to radiation therapy: the previous TURP of the prostate, pronounced obstructive symptoms, inflammatory bowel disease.

In the approaches to radiation therapy, the authors have significant differences in the techniques and methods of irradiation, the amount of radiation exposure and the total focal doses.

The main serious side effects of radiation therapy are associated with damage to the microcirculation of the bladder, rectum and its sphincter, urethra. Approximately one third of patients have symptoms of acute proctitis and cystitis during the course of radiation therapy. At 5-10% there are constant symptoms (irritable bowel syndrome, recurrent bleeding from the rectum, symptoms of bladder irritation and periodic macrohematuria). The incidence of late complications after radiation therapy according to the European Organization for Research and Treatment of Cancer: cystitis 5.3%, hematuria 4.7%, urethral stricture 7.1%, urinary incontinence 5.3%, proctitis - 8.2%, chronic diarrhea - 3.7%, small intestinal obstruction - 0.5%, lymphostasis of the lower extremities - 1.5%. Approximately half of the patients experience impotence. Which usually develops approximately 1 year after completion of treatment. This is due to damage to the blood supply of the cavernous nerves and cavernous bodies of the penis

Localized prostate cancer: radiation therapy

For patients with Tl-2aN0M0 tumors, a Gleason score of 6 or less and a PSA of less than 10 ng / mL (low-risk group), radiation therapy at a dosage of 72 Gy is recommended. It was demonstrated that the disease-free survival rate is higher at a dose of 72 Gy and more, compared with a dose less than 72 Gy.

According to a number of studies, with a tumor of T2b or a PSA level of 10-20 ng / ml. Or a Gleason score of 7 (medium risk group), increasing the dose to 76-81 Gy significantly improves 5-year recurrence-free survival without causing serious complications. For daily practice use a dose of 78 Gy.

With tumor T2c or the amount of PSA is more than 20 ng / ml. Or Gleason's sum more than 7 (high-risk group), the escalation of the radiation dose increases the disease-free survival rate, but does not prevent recurrence outside the pelvic floor. In one randomized trial from France, a dose advantage of 80 Gy versus 70 Gy is indicated.

For conformal radiotherapy with dose escalation, impressive results were obtained, indicating an increase in 5-year disease-free survival from 43 to 62% with an increase in the radiation dose from 70 to 78 Gy for patients with intermediate and high-risk prostate cancer. If the depth of germination of the primary tumor is T1 or T2, the Gleason sum is not more than 7, the PSA level is not more than 10 ng / ml, the disease-free survival rate is 75%.

There are no completed randomized trials indicating that the addition of antiandrogen treatment to radiation therapy has the advantage in high-risk patients with localized prostate cancer. However, based on studies on locally advanced prostate cancer, the appointment of hormonal treatment in conjunction with radiation therapy is supported in high-risk patients with localized prostate cancer.

The use of antiandrogens for 6 months (2 months before the beginning, 2 months at the time and 2 months after radiation therapy) improves the results of treatment in patients with moderate-risk prostate cancer. Lugovaya therapy with locally advanced prostate cancer Treatment with antiandrogens for 3 years. Prescribed together with radiation therapy. Improves survival in patients with locally advanced prostate cancer. Combination of antiandrogen treatment before, during and after radiotherapy for 28 months compared with 4 months of hormone therapy before and during irradiation has the best oncological indicators of treatment effectiveness with the exception of overall survival. The benefit of overall survival with longer hormone therapy in combination with radiotherapy is proven for patients with locally advanced prostate cancer with a Gleason score of 8-10.

Evaluation of the results of radiation therapy is not an easy task, because cancer cells do not die right after irradiation. Their DNA gets lethal damage, and cells do not die until they attempt to divide the next. Thus, the level of PSA gradually decreases within 2-3 years after completion of radiation therapy. In accordance with this, the PSA level is examined every 6 months. It does not reach the lowest value (nadir). In patients. Subjected to radiotherapy, the prostate does not completely collapse, and the remaining epithelium continues to produce PSA. In addition, prostate inflammation can cause a temporary rise in PSA, called a "jump" of PSA.

The biochemical reference point used to determine the success of treatment after remote radiation therapy is contradictory. Optimum decrease in the amount of PSA is less than 0.5 ng / ml, this allows predicting a favorable outcome after irradiation. In the American Association of Therapeutic Radiology and Oncology, biochemical recurrence after radiotherapy is considered to be more than 2 ng / ml PSA, provided that this PSA level is greater than the minimum (nadir). By the level of PSA after radiation therapy, it is possible to predict the nature of relapse. In patients with local recurrence, the PSA doubling time is 13 months. In patients with systemic relapse - 3 months. Radiation therapy after radical prostatectomy The need for adjuvant radiotherapy or expectant management with salvage radiation therapy in the event of recurrence after RP is being discussed at the present time. Randomized trials comparing adjuvant radiation with early salvage radiotherapy after surgery are not. There are only data confirming the advantage of survival in adjuvant radiation therapy in comparison with observation in patients with a positive surgical margin, extracalcular extensia and invasion of seminal vesicles. Rescue remote radiation therapy is performed with relapse, until the PSA level reaches 1 -1.5 ng / ml.

In patients at high risk with localized prostate cancer, a combination of brachytherapy with remote radiation therapy is possible. In this case, brachytherapy is performed first.

Recently, remote radiation therapy with heavy particles (high-energy photons and neutrons) is positioned as a more effective method of conformal irradiation, but there is no convincing evidence of superiority over standard photon irradiation. Moreover, a higher incidence of urethral stricture after heavy particles was noted.

In modern studies, the possibility of using higher doses of irradiation in metabolically more active foci according to magnetic resonance spectroscopy is being studied.

It should be noted that the main point of application of radiotherapy for prostate cancer is a localized tumor. The appearance of three-dimensional conformal radiation therapy and the modulation of the intensity of irradiation, as one of its perfect forms, made it possible to increase the dose of radiation, reduce the complications of traditional radiotherapy, and obtain oncological results competing with radical surgical treatment.