**4. Postoperative radiotherapy in prostate cancer**

Radical prostatectomy is proven treatment modality for prostate cancer control for a long time. Some authors report 10-year cancer-specific survival of 85-90% in localized prostate cancer after radical prostatectomy, and 82% at 15 years. Survival is better if the tumor is low grade i.e. low Gleason score and low stage.

The risk of surgical margins positivity is of great concern after radical prostatectomy. Positive margins are noticed in 28% of patients with T1-T2 prostate cancer and prostate apex is the most common site. For T3 cancers this percent is even higher-up to 52%.

High tumor stage (T3a and T3b) and a positive surgical margin are strong predictors of local recurrence, biochemical and clinical failure. In general, it is considered that the percent of local recurrence after radical prostatectomy ranges about 15% for T2 prostate cancers, and 50-70% for T3 tumors.

In order to analyze the impact of predictive factors on development of local recurrence, univariate and multivariate analyzes were performed. In univariate analyzes strong predictors of local relapse are high-grade cancer, positive surgical margins and involvement of seminal vesicles. In multivariate analyzes these predictors are high-grade tumor, positive surgical margin and elevate prostatic phosphatase.

Identification of patients that are candidates for adjuvant therapies after radical prostatectomy is still a great issue. The adequate treatment modality for these patients is an open question too. There is no consensus yet.

Mild and transient acute urinary symptoms (dysuria and hematuria of grade G1) followed HDR brachytherapy in about 50% of patients in the first week or two, and persist for up to 6 months in less than 35% of treated patients, while grade G2 symptoms occurred in about 11 % of patients in the first weeks after treatment and after 6 months they completely disappeared. Pronounced symptoms of grade G3 (urethral stricture at the level of bladder base) are very rare (less than 2%), and they require a retention of urinary catheter, and usually occur immediately after irradiation, and disappear within ten days. Acute symptoms of grade G1 rectum (proctitis, tenesma and bleeding) are rare and mainly are result of edema and hematoma, and occur in less than 25% of patients in the first weeks and decrease to about 8% in the 6-month after conducted therapy. Acute complications of

All listed acute symptoms may be connected to radiation and trauma during application

The frequency and severity of late complications after HDR brachytherapy is similar to the permanent implant brachytherapy (LDR), except that complications associated with the

When HDR brachytherapy (22-24 Gy/5-6 fr.) is applied in combination with transcutaneous radiotherapy (EBRT to 40Gy), the results of treatment (five-year survival NED/biochemical/and overall survival) of 63% in patients with high risk are comparable and slightly better than with the application of brachytherapy (LDR and HDR) as a monotherapy. (Deamens et al., 2009) In the same paper, the authors conclude that no benefit was noted when

Acute and late effects on the bladder and rectum are more pronounced in cases of combined

Radical prostatectomy is proven treatment modality for prostate cancer control for a long time. Some authors report 10-year cancer-specific survival of 85-90% in localized prostate cancer after radical prostatectomy, and 82% at 15 years. Survival is better if the tumor is low

The risk of surgical margins positivity is of great concern after radical prostatectomy. Positive margins are noticed in 28% of patients with T1-T2 prostate cancer and prostate apex

High tumor stage (T3a and T3b) and a positive surgical margin are strong predictors of local recurrence, biochemical and clinical failure. In general, it is considered that the percent of local recurrence after radical prostatectomy ranges about 15% for T2 prostate cancers, and

In order to analyze the impact of predictive factors on development of local recurrence, univariate and multivariate analyzes were performed. In univariate analyzes strong predictors of local relapse are high-grade cancer, positive surgical margins and involvement of seminal vesicles. In multivariate analyzes these predictors are high-grade tumor, positive

Identification of patients that are candidates for adjuvant therapies after radical prostatectomy is still a great issue. The adequate treatment modality for these patients is an

is the most common site. For T3 cancers this percent is even higher-up to 52%.

procedure, although problems have not been noted during the application itself.

applying deprivate androgen therapy in relation to combined radiotherapy.

**4. Postoperative radiotherapy in prostate cancer** 

**3.2.2 Toxicity of high dose rate brachytherapy** 

grade G3 were not observed.

migration of radiation sources do not occur.

radiotherapy, which can be expected.

grade i.e. low Gleason score and low stage.

surgical margin and elevate prostatic phosphatase.

open question too. There is no consensus yet.

50-70% for T3 tumors.

After radical prostatectomy, the application of radiotherapy can lower the incidence of local relapses, but its effect on distant metastases appearance is not confirmed. Alternative regimen is the use of androgen-deprivation therapy alone or in combination with radiotherapy which can also improve local control and eradication of distant metastases. (Hadzi-Djokic, 2005)

Three randomized trials (Bolla, Wiegel & Thompson), have shown an advantage in biochemical relapse-free survival with postoperative radiotherapy for men with positive surgical margins or pT3 disease. These trials compared postoperative radiotherapy with 60- Gy to the prostatic fossa to radical prostatectomy alone in men with high-risk prostate cancer. With the use of postoperative irradiation the 5-year biochemical progression-free survival was significantly improved, as well as clinical progression-free survival. Thompson's trial has also show an advantage of overall survival (10.3 years for irradiated patients after prostatectomy to 3.1 year for prostatectomy only). Bolla failed to demonstrate this advantage. That means that not all men with adverse prognostic factors will relapse. Also, not all men treated with postoperative radiotherapy will be cured. Combined treatment is also associated with greater toxicity than radiotherapy or prostatectomy alone. So what will the optimal treatment be? (Hayden et al., 2010, Bolla et al., 2005, Wiegel et al., 2009, Thompson et al., 2009) Eastham et al. managed to give actually 4 possible scenarios for post-prostatectomy setting: (1) there is no residual disease and adjuvant radiation is not necessary; (2) persistent disease is present in the prostatic fossa only and adjuvant irradiation may provide long-term cure; (3) there is a residual local disease as well as microscopic disseminated disease and adjuvant irradiation may eradicate local disease but will have no impact on the systemic component; (4) disease is only systemic and adjuvant local irradiation is not necessary.

Salvage radiotherapy in the setting of a rising PSA after prostatectomy is unproven and still controversial. This is most likely the result of inadequately selected patients for postprostatectomy irradiation. Many of them already have systemic recurrence so a detail diagnostic workout is necessary. (Eastham et al., 2010)

The special issue is the use of adjuvant hormone therapy. Some studies show that the application of adjuvant hormone therapy reduces the risk of positive surgical margins, improves local disease control, eradicates micro metastases and prolongs time to progression and overall survival. On the other hand, neoadjuvant hormone therapy, prior to surgery, in order to downstage the disease, has not been proven for successes neither in preventing biochemical or clinical relapse nor in improving survival so in most centres it is deserted. (Dearnaley, 2005)
