Radical prostatectomy

Radical prostatectomy (RP) is the removal of the prostate gland and seminal vesicles via a retropubic or perineal approach. Laparoscopic and robot-assisted laparoscopic prostatectomy are becoming increasingly common. The use of minimally invasive prostatectomy techniques allows for earlier patient activation and a shorter hospital stay.

Radical prostatectomy was first performed in 1866, and in the early 20th century, a perineal approach was used. Later, a retropubic approach was proposed. In 1982, the anatomy of the venous plexus and vascular-nerve bundles of the prostate gland was described, which made it possible to significantly reduce blood loss, the risk of impotence and urinary incontinence.

Prostatectomy is the only treatment method that has been shown in a randomized trial to reduce the risk of death from the tumor compared to dynamic observation. Its main advantage is the possibility of complete cure of the underlying disease. When performed by an experienced doctor, the operation is associated with a minimal risk of complications and provides a high chance of recovery. However, it should be taken into account that radical prostatectomy is a complex operation with a very long "learning curve".

Retropubic access is used more often, as it allows for removal of pelvic lymph nodes. Given the anatomical features of the fascial cover of the gland (thinning in the anterior sections), with perineal access there is a high probability of preserving tumor cells in the resection zone. Probably, with perineal prostatectomy and laparoscopic lymphadenectomy, complications occur less frequently than with surgery with retropubic access. In recent years, some European centers have mastered laparoscopic prostatectomy. Despite the fact that data on long-term results have not yet been obtained, this method is gaining popularity.

Advantages and disadvantages of retropubic radical prostatectomy

Advantages	Disadvantages
Excellent long-term survival results	Risk of postoperative mortality and complications
Accuracy of staging and prognosis	Risk of incomplete organ removal (positive surgical margin)
Possibility of simultaneous lymphadenectomy	Risk of permanent urinary incontinence or erectile dysfunction
Management of complications	Visible skin scar, possibility of developing postoperative hernia
Early detection of recurrence by PSA level and the possibility of other treatment methods (radiation, HIFU, hormonal therapy)	Hospitalization, temporary disability

In the case of a localized tumor and a life expectancy of about 10 years or more, the goal of surgery (regardless of access) should be a cure. In case of refusal of treatment, the risk of death from the underlying disease within 10 years is 85%. The patient's age cannot be an absolute contraindication to surgery, however, with increasing age, the number of concomitant diseases increases, therefore after 70 years the risk of death directly from localized prostate cancer is significantly reduced.

An important issue is maintaining potency after surgery. The urologist's task is to assess the degree of risk and the need to preserve the vascular-nerve bundles responsible for erectile function. Nerve-sparing surgery is indicated for a limited number of patients who meet the following pre-surgery requirements: initially preserved potency and libido, low oncological risk (PSA level less than 10 ng/ml, Gleason index more than 6). Otherwise, there is a high risk of local relapse. With a high oncological risk, such patients are indicated for postoperative external beam radiation therapy, therefore, preserving the vascular-nerve bundles is inappropriate. To resume sexual activity after surgery, it is possible to use phospholiesterase type 5 inhibitors (sildenafil, tadalafil), intracavernous injections (alprostadil), and vacuum erectors. In case of complete loss of function, penile prosthesis is possible. If the patient insists on preserving the vascular-nerve bundles, it is necessary to inform him about the time frame for restoration of potency (6-36 months), the risk of developing Peyronie's disease with incomplete rigidity of the penis and the possibility of complete loss of erectile function.

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Preoperative preparation for radical prostatectomy

On the eve of the operation, fluid intake is limited, a cleansing enema is performed in the morning before the operation. One hour before the operation, a single administration of antibiotics (fluoroquinolones or cephalosporins of the III-IV generation) is indicated. The operation can be performed under epidural anesthesia or endotracheal anesthesia. A mandatory condition is compression bandaging of the lower extremities to prevent thromboembolic complications.

The main stages of retropubic RPE:

• Pelvic lymphadenectomy.
• Dissection of the pelvic fascia.
• Transection of the puboprostatic ligaments (possible after suturing the dorsal venous complex - DVC).
• Stitching, ligation and intersection of the DVC.
• Urethral transection.
• Isolation of the prostate gland, seminal vesicles and vas deferens.
• Severing the prostate gland from the bladder.
• Reconstruction of the bladder neck.
• Creation of an anastomosis between the bladder and urethra.
• Drainage of the perivesical space.

The operation lasts 2-3 hours. Patients are mobilized the day after the operation. Drains are removed as the wound discharge decreases (less than 10 ml). The urethral catheter is removed on the 8th-12th day. Kegel exercises are recommended to restore complete urine continence. In the early postoperative period, absorbent pads are used in case of urine dripping. PSA levels are monitored every 3 months after the operation.

Morphological examination of a macropreparation

A full examination of an organ removed by RPE requires a large number of blocks, which leads to significant economic costs. However, failure to comply with the examination protocol significantly complicates the clarification of the stage of the disease and the decision on the tactics of further treatment. The description of the macropreparation should contain the following information: description of the removed organ or tissue, weight (g), size (cm) and number of samples, description of the tumor node (localization, size, type, edge). The histological report must indicate: histological type, Gleason differentiation grade, extent of tumor spread, lymphatic and venous invasion, damage to the seminal vesicles and lymph nodes.

Extraprostatic spread is tumor growth into adjacent non-glandular tissues. Criteria for prostate cancer spread beyond the gland capsule are based on detection of components that form the extra-organ tumor focus: tumor cells in adipose tissue, anterior muscle group, carcinoma in perineural spaces of vascular-nerve bundles. The extent of the lesion (which has an important prognostic value) can be focal (several tumor foci outside the prostate gland) and diffuse (all other cases). Removal of the seminal vesicles, despite the data of the preoperative examination, is performed in full, which is associated with the mechanism of tumor spread. It can occur by direct growth upward, into the seminal vesicle complex, by spreading from the base of the gland or surrounding adipose tissue, or in isolation as a single metastasis without connection with the primary focus.

_{T1a -2c} tumors (localized prostate cancer)

In T _1a tumors with Gleason score 2-4, the risk of progression without treatment is 5% with observation for 5 years, but after 10-13 years it reaches 50%. Thus, in patients with a life expectancy of 15 years or more, this risk is quite high. At the same time, most T _1a and T _1b tumors progress within 5 years and require radical treatment. This is why a prostate biopsy after 3 months is recommended for the diagnosis of T _1a and T _{1b tumors. For T1b} tumors and a life expectancy of more than 10 years, prostatectomy is indicated. After extensive transurethral resection, radical prostatectomy is technically more difficult to perform.

The most frequently diagnosed tumor is T1c _. In each case, it is difficult to predict the clinical significance of the tumor. According to most studies, T1c tumors _usually require treatment, since about a third of them are locally advanced. The proportion of clinically insignificant tumors is 11-16%. With an increase in the number of biopsies, this indicator may increase, although taking 12 biopsies usually does not increase it.

Prostate dysplasia is not considered an indication for treatment, but after 5 years, cancer is detected in 30% of patients with severe dysplasia, and after 10 years - in 80%. Mild dysplasia is also dangerous: the risk of cancer in subsequent biopsies is comparable to that in severe dysplasia. However, in the absence of cancer, radical prostatectomy is not recommended, since dysplasia can be reversible.

It is important to determine which T1c tumors _can avoid prostatectomy. Biopsy data and free PSA levels can help predict tumor significance; Partin nomograms can be very helpful. Some physicians prefer to rely on biopsy results: if cancer is found in only one or a few biopsies and occupies a small part of the biopsy, the tumor is likely not clinically significant (especially with a low Gleason score). In some such cases, dynamic observation is justified. However, prostatectomy should usually be recommended for T1c tumors _, since most of these tumors are clinically significant.

Radical prostatectomy is one of the standard methods of treating T2 tumors with a life expectancy of more than 10 years. If the tumor is limited to the prostate gland during morphological examination, the prognosis is favorable even with a low degree of differentiation (although such tumors usually extend beyond the gland). With a high degree of differentiation, dynamic observation is also possible, but it should be remembered that biopsy often underestimates the Gleason index.

_T2 tumors tend to progress. Without treatment, the median time to progression is 6-10 years. Even with T2a tumors, _the risk of progression within 5 years is 35-55%, so with a life expectancy of about 10 years or more, prostatectomy is indicated. With T2b tumors, _the risk of progression exceeds 70%. The need for surgery is supported by a comparison of prostatectomy with dynamic observation (most patients in this study had T2 tumors ₎. In relatively young patients, prostatectomy is the optimal treatment, but in older patients with severe comorbidities, radiation therapy is better used.

Surgeon experience and surgical technique can improve the results of surgical treatment of prostate cancer.

_T3 tumors (locally advanced prostate cancer)

The proportion of locally advanced tumors is currently gradually decreasing (previously they were at least 50%), but the optimal tactics when they are detected are still controversial. Prostatectomy often does not allow for complete removal of the tumor, which dramatically increases the risk of local recurrence. In addition, surgical complications with prostatectomy occur more often than with localized tumors. Most patients develop metastases to the lymph nodes and distant metastases. Thus, surgery for T3 tumors _is usually not recommended.

Combination therapy with hormonal therapy and radiation is increasingly being used, although it has not been proven to be superior to prostatectomy alone. A randomized trial showed superiority of combined treatment over radiation alone, but there was no surgical control group. Evaluation of the results of prostatectomy is also complicated by the frequent use of concomitant adjuvant radiation therapy and immediate or delayed hormonal therapy.

About 15% of tumors clinically assessed as T3 _{were localized (pT2} ) at surgery, and only 8% were widespread (pT4 ₎. In the former case, the prognosis is favorable, but most patients with pT3b tumors _experienced early relapses.

The 5-year relapse-free survival (PSA level zero) for T3 tumors _is about 20%. The prognosis depends on the Gleason index. Histological examination of the removed prostate most often reveals moderately and poorly differentiated cells. In addition to the degree of cell differentiation, other independent unfavorable prognostic factors include seminal vesicle invasion, lymph node metastasis, detection of tumor cells at the resection margin, and a high PSA level (more than 25 ng/ml).

_{In T3a} tumors and PSA levels below 10 ng/ml, 5-year relapse-free survival usually exceeds 60%. Thus, surgery can help not only those patients whose clinical stage was overestimated, but also those with true T3a _. Surgery is ineffective in patients with lymph node metastases and seminal vesicle invasion. Partin nomograms are used to detect these data. In addition, MRI helps assess the condition of the lymph nodes and seminal vesicles.

Surgeries for T3 tumors _require highly qualified surgeons, which reduces the risk of complications and improves functional results.

Metastasis to the lymph nodes

Lymph node dissection may be omitted in cases of low oncological risk, but its implementation allows for a more accurate staging of the disease and detection of micrometastasis. Metastases in the lymph nodes are precursors of distant metastases. After surgery, such patients usually experience a relapse. The importance of frozen section lymph node examination during surgery is not clearly defined, but most urologists strive to perform extended lymph node dissection, refuse prostatectomy in cases of significant lymph node enlargement (usually disseminated tumors that are subject to hormone therapy only), and stop the operation if urgent histological examination reveals metastasis. It has been noted that routine examination of removed lymph nodes can help detect micrometastases. With single lymph node metastases or micrometastases, the risk of relapse is lower. In case of metastases to distant lymph nodes, adjuvant hormonal therapy is possible, but since it is associated with side effects, sometimes observation can be limited, postponing hormonal therapy until the PSA level increases.

Some surgeons always perform extended pelvic lymphadenectomy (including, in addition to the obturator nodes, the external and internal iliac and sacral lymph nodes), but this approach requires randomized trials. In recent years, lymphadenectomy has increasingly been given not only diagnostic but also therapeutic value.

Remote results

In the further monitoring of cancer patients, the pathological stage (pT) indicating the purity of the surgical margin, postoperative PSA level (biochemical recurrence), local recurrence, metastasis, cancer-specific survival, and overall survival are of great importance. The relapse-free course of the disease depends on clinical and pathomorphological data. Independent prognostic factors include clinical stage, Gleason grading, and PSA level. Additional factors include capsule penetration (extracapsular extension), perineural and/or lymphovascular invasion, involvement of the lymph nodes and seminal vesicles.

Complications of radical prostatectomy

The overall complication rate after retropubic radical prostatectomy (with sufficient surgeon experience) is less than 10%. Early complications may include bleeding, damage to the rectum, ureters, obturator nerves, anastomotic failure, vesicorectal fistula, thromboembolic complications, cardiovascular pathology, ascending urinary infection, lymphocele, and postoperative wound failure. Late complications may include erectile dysfunction, urinary incontinence, urethral or anastomotic strictures, and inguinal hernias.

Complications of radical prostatectomy

Complications	Risk, %
Mortality	0-2.1
Severe bleeding	1-11
Rectal injury	0-5.4
Deep vein thrombosis of the pelvis	0-8.3
Pulmonary embolism	0.8-7.7
Lymphocele	1-3
Vesicorectal fistula	0.3-15.4
Stress urinary incontinence	4-50
Total urinary incontinence	0-15.4
Erectile dysfunction	29-100
Anastomotic stricture	0.5-14.6
Urethral stricture	0-0.7
Inguinal hernia	0-2.5

Careful adherence to indications for surgical intervention reduces the risk of postoperative mortality to 0.5%.

Usually, the volume of blood loss does not exceed 1 liter. An uncommon but serious complication is damage to the ureter. In case of a minor defect, suturing the wound and drainage with a catheter (stent) is possible. In case of more extensive damage or intersection of the ureter, ureterocystoneostomy is indicated. A minor defect of the rectum can also be sutured with a double-row suture after devulsion of the anus. Anus preater naturalis is applied in case of a significant defect or previous radiation therapy.

The urinary continence function is restored faster than the erectile function. About half of the patients retain urine immediately after the operation, while the rest recover within a year. The duration and severity of urinary incontinence directly depends on the patient's age. 95% of patients under 50 are able to retain urine almost immediately, and 85% of patients over 75 suffer from incontinence of varying degrees. In case of total urinary incontinence, the installation of an artificial sphincter is indicated. Erectile dysfunction (impotence) has previously occurred in almost all patients. In the early stages, it is possible to perform an operation to preserve the cavernous nerves, but it increases the risk of local relapse and is not recommended for low-differentiated tumors, invasion of the apex of the prostate gland, and palpable tumors. Unilateral preservation of the cavernous nerve also gives good results. Injections of alprostadil into the cavernous bodies in the early postoperative period help reduce the risk of impotence.

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Clinical guidelines for performing radical prostatectomy

Indications:

• stage T _1b 2Nx-0, M0 with life expectancy over 10 years;
• _{T 1a} tumors with a very long (more than 15 years) life expectancy;
• _T3a tumors with a Gleason score of more than 8 and a PSA level of more than 20 ng/ml.

At stage T _1-2, a 3-month course of neoadjuvant therapy is not recommended.

Preservation of the cavernous nerves is possible only with a low oncological risk (T1c _, Gleason index less than 7, PSA level less than 10 ng/ml).

In stage T _2a, it is possible to perform prostatectomy with unilateral preservation of the cavernous nerve.

The advisability of radical prostatectomy in patients with a high risk of distant metastasis| metastasis to the lymph nodes, as well as in combination with long-term hormonal therapy and adjuvant radiotherapy has not been sufficiently studied.

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