**2. Defining high risk prostate cancer**

The factors that best define the high risk prostate cancer are those described by D'Amico (11) approved by the American Urological Association in 2007 are:

Gleason ≥ 8 points and / or PSA ≥ 20 and / or clinical stage ≥ T2c

These high-risk tumors are at high risk for recurrence, either local or remote, so they are also traditionally called "locally advanced" (12) or "poorly differentiated" (13). If the patient has the 3 items they are considered "very high risk" and have a high probability to die from prostate cancer (14).

Another factor that has been added as a fourth factor is pretreatment *PSA velocity* which if greater 2ng/ml/year is included as criteria for high-risk disease (15,16).

The simplification of the term "risk" has led many doctors to select patients and improperly included in high-risk groups. Also, following the analysis of these high-risk criteria, we can not quantify the individual risk to a patient, for example, with stage T2c and Gleason 8 would have the same risk that a patient with a PSA 70 and stage T3a (17). That is why this classification system is inadequate and we must use another tool to individualize the risk of each patient; this tool are *Nomograms* which individually allow to analyze and quantify the risk presented by each patient in response to multiple risk factors or variables, integrated in a complex mathematical formula (18). There are plenty of nomograms (19) that have been designed for use in prostate cancer in recent years and could be classified into 3 groups:

*Diagnostic nomograms:* those who pretend to estimate the probability of a patient developing prostate cancer. For example, the Vienna nomogram (20) that analyzes the number of cylinders to take a biopsy of the prostate.

*Staging nomograms*: such as the Partin tables (21), which indicates the likelihood of organconfined disease. Or A. Borque neural network for predicting pathological stage in men undergoing radical prostatectomy. (22)

Radical Prostatectomy in High Risk Prostate Cancer 137

Various studies such as those of Mian et al (39), Lau et al (40) and Soloway et al (41) analyze

The clinical Gleason 8-10 is an independent prognostic factor for biochemical progressionfree survival. The radical prostatectomy remains one of the most valid treatments for these

**T1c** 55% 50% 0,0001

**pT3b** 69% 44% 0,0001

**Surgical Margin-** 67% 48% 0,0001

**Progression -** 74,3% 52,5% 0,0001

Different studies show that the RP in patients with a PSA> 20 is associated with a high recurrence rate, D'Amico and colleagues found that males with a PSA level higher than 20 ng/ml had risk recurrence of 50% at 5 years after RP (42). Similarly, Yossepowitch published the results of their series of patients with PSA> 20ng/ml who underwent radical prostatectomy, showing a PSA recurrence rate of 44 and 53% at 4 and 20 years respectively (10). It is perhaps the high preoperative PSA, the factor that best relates to a worse prognosis

On the other hand, Inman and colleagues, in their series of patients with PSA> 50ng/ml who underwent RP with multimodal adjuvant therapy, had biochemical progression-free survival at 10 years of 83% with a cancer-specific survival 87% (43). These highlights the

The lack of evidence regarding the effectiveness of treatment options for clinically localised prostate cancer continues to impact on clinical decision-making. The two such options are

For the majority of men with favorable-risk localized disease, older than 65, surveillance will be an attractive option that avoids adverse effects of treatment(45). But the existing trials,

**Group Gleason 2-7 Group Gleason 8-10 P value** 

Av. 16,89

Median 12 0,01

and study the survival in these patients concluded similarly.

**Nº of patients** 673 108

**>T1c** 45% 50%

**pT3b** 30% 56%

**Surgical Margin +** 33% 53%

**Progression +** 25,7% 47,5%

potential benefit of surgery with in a multimodal approach.

**3. Therapeutic options in "high risk" prostate cancer** 

radical prostatectomy (RP) and active surveillance (AS). (44)

Median 9,8

**PSA (ng/ml)** Av 13,48

**2.3 Prostate cancer with PSA > 20** 

**Biochemical** 

**Biochemical** 

preoperatively.

**3.1 Introduction** 

**Localized prostate cancer** 

Table 2.

short of patients and providing good oncological and functional outcomes.

*Prognostic nomograms*: are tools that estimate the probability of success in applying a certain treatment to analyze different variables. The most famous and globally applied is Kattan nomogram (23). It analyzes a combination of three factors to determine the probability of PSA relapse after local therapy. These factors are: PSA, Gleason score and clinical stage. They apply both to radical prostatectomy, radiotherapy and brachytherapy. Nomograms derived from the results of treating thousands of patients. The statistical probability of relapse depends on the presence of pre-existing micro metastases at the time of local therapy (23). Hence the likelihood of relapse determined by the Kattan nomograms can be taken as an indication of the presence of micro metastases at the time of local therapy, resulting in an estimate to calculate the probability of success / failure when applying a certain treatment.

In summary, nomograms are useful modern tools that exist today, which may help us making treatment decisions in patients with prostate cancer, especially those with high-risk prostate cancer. As well as providing more information to the patient.

#### **2.1 Locally advanced prostate cancer cT3a**

When the disease has overpassed the prostate capsule, it is a T3a stage. Typically, when a patient is at this stage we are advise against radical prostatectomy (24) as primary treatment based on the high rate of positive surgical margins and lymph node metastases (25,26). Numerous studies have shown that the risk/benefit of a radical prostatectomy is even more clear in the treatment of high risk prostate cancer (27-32), but unfortunately, there are not studies comparing combination therapy (radiotherapy plus hormones) with RP.

Between 13% and 27% of patients diagnosed with stage T3 are overstimated (31,32).

The development of CT imaging or MRI, as well as directed needle biopsies of lymph nodes or seminal vesicles (32), help identify patients who have less probability to benefit from a surgical treatment (33) as well as to plan surgery upon results.

Due to an increased sophistication and experience of the different surgical techniques, there has been a decreased in operative morbidity and better functional outcomes after RP in stage T3 cancer than before (31,33). Urinary incontinence and erectile dysfunction remain the two major consequences of the surgery, but due to surgical expertise and experience, as well as a proper surgical planning, an improvement in functional results has been shown (35).

#### **2.2 High grade prostate cancer: Gleason score 8-10**

Patients with high Gleason score 8-10 tumors, which are confined to the prostate on histopathological examination, they still have a good prognosis after RP (36). The differences between the Gleason score biopsy and the Gleason score regarding the surgical specimen are between 36 and 60% of cases, although a study by Dr. Grossfeld (37) shows that 39% of patients had Gleason 8-10 in the biopsy specimen, showed a Gleason score of 7 or less in the prostatectomy speciem.

In a recent publication (38) in which the outcome of 781 patients undergoing RP clinically localized stages T1-T2 was analysed, they divided into 2 groups according to Gleason: Gleason patients 2-7 and another group with Gleason 8-10. Over all, they showed a worse prognostic features and higher PSA relapse. (Table 2)

Patients with Gleason score 8-10 prostate cancer have a higher likelihood of recurrence, but due to the PSA era, many of these patients are diagnosed with an early stage and therefore a potential local curative treatment is applicable successful (38).

Various studies such as those of Mian et al (39), Lau et al (40) and Soloway et al (41) analyze and study the survival in these patients concluded similarly.

The clinical Gleason 8-10 is an independent prognostic factor for biochemical progressionfree survival. The radical prostatectomy remains one of the most valid treatments for these short of patients and providing good oncological and functional outcomes.


Table 2.

136 Prostate Cancer – Diagnostic and Therapeutic Advances

*Prognostic nomograms*: are tools that estimate the probability of success in applying a certain treatment to analyze different variables. The most famous and globally applied is Kattan nomogram (23). It analyzes a combination of three factors to determine the probability of PSA relapse after local therapy. These factors are: PSA, Gleason score and clinical stage. They apply both to radical prostatectomy, radiotherapy and brachytherapy. Nomograms derived from the results of treating thousands of patients. The statistical probability of relapse depends on the presence of pre-existing micro metastases at the time of local therapy (23). Hence the likelihood of relapse determined by the Kattan nomograms can be taken as an indication of the presence of micro metastases at the time of local therapy, resulting in an estimate to calculate the probability of success / failure

In summary, nomograms are useful modern tools that exist today, which may help us making treatment decisions in patients with prostate cancer, especially those with high-risk

When the disease has overpassed the prostate capsule, it is a T3a stage. Typically, when a patient is at this stage we are advise against radical prostatectomy (24) as primary treatment based on the high rate of positive surgical margins and lymph node metastases (25,26). Numerous studies have shown that the risk/benefit of a radical prostatectomy is even more clear in the treatment of high risk prostate cancer (27-32), but unfortunately, there are not

The development of CT imaging or MRI, as well as directed needle biopsies of lymph nodes or seminal vesicles (32), help identify patients who have less probability to benefit from a

Due to an increased sophistication and experience of the different surgical techniques, there has been a decreased in operative morbidity and better functional outcomes after RP in stage T3 cancer than before (31,33). Urinary incontinence and erectile dysfunction remain the two major consequences of the surgery, but due to surgical expertise and experience, as well as a proper surgical planning, an improvement in functional results

Patients with high Gleason score 8-10 tumors, which are confined to the prostate on histopathological examination, they still have a good prognosis after RP (36). The differences between the Gleason score biopsy and the Gleason score regarding the surgical specimen are between 36 and 60% of cases, although a study by Dr. Grossfeld (37) shows that 39% of patients had Gleason 8-10 in the biopsy specimen, showed a Gleason score of 7 or less in the

In a recent publication (38) in which the outcome of 781 patients undergoing RP clinically localized stages T1-T2 was analysed, they divided into 2 groups according to Gleason: Gleason patients 2-7 and another group with Gleason 8-10. Over all, they showed a worse

Patients with Gleason score 8-10 prostate cancer have a higher likelihood of recurrence, but due to the PSA era, many of these patients are diagnosed with an early stage and therefore a

studies comparing combination therapy (radiotherapy plus hormones) with RP. Between 13% and 27% of patients diagnosed with stage T3 are overstimated (31,32).

prostate cancer. As well as providing more information to the patient.

surgical treatment (33) as well as to plan surgery upon results.

**2.2 High grade prostate cancer: Gleason score 8-10** 

prognostic features and higher PSA relapse. (Table 2)

potential local curative treatment is applicable successful (38).

when applying a certain treatment.

has been shown (35).

prostatectomy speciem.

**2.1 Locally advanced prostate cancer cT3a** 
