**3.3 Objectives of treatment in high risk prostate cancer**

The actual objectives of the treatment of high prostate cancer are:


Men with high-volume lesions or high-stage yet clinically localized disease must receive multimodal therapy. More advances will require concerted efforts through clinical trials. (45)

Neoadjuvant Androgen Deprivation Therapy may indeed provide no additional benefit over surgery alone for patients with clinically localized prostate cancer. Recent studies have demonstrated the feasibility of neoadjuvant chemotherapy prior to RP in patients with highrisk prostate cancer. (17). If such a strategy was shown to be effective, future clinical practice could be altered significantly. A randomized phase 3 clinical trial, CALGB 90203, is currently investigating whether neoadjuvant chemo-hormonal therapy followed by RP reduces the risk of biochemical recurrence when compared to RP alone.

#### **3.4 Actual treatment in high risk prostate cancer**

Actually, the optimal treatment are:


There is no consensus regarding the optimal treatment of men with high-risk PCa.

Surgery is showing good results, but decisions on whether to elect surgery as local therapy should be based on the best available clinical evidence. (49)

On the other hand, it has been recently assessed the effect of RP and RT on the rate of distant metastases in patients with clinically localized prostate cancer on the study from Memorial Sloan Kettering Cancer Center comparing patients whom underwent surgery versus radiotherapy (50). Patients with clinical stages T1c-T3b prostate cancer treated with intensity-modulated RT (81 Gy) from 1998 to 2002 were compared with similar cohort of men treated with RP.

This study, showed that patients with higher-risk disease, treated with RP had a lower risk of metastatic progression and prostate cancer-specific death, than men treated with RT. The metastatic progression is infrequent in men with low-risk prostate cancer, treated with either RP or RT.

These results, despite being from retrospective review of patients treated at a single institution, certainly suggest that RP should be considered as a treatment option in men with clinically localized, high-risk prostate cancer. (50)

Radical Prostatectomy in High Risk Prostate Cancer 141

The problem remains on patient selection before surgery: Nomograms, nodal imaging with CT and seminal vesicle imaging with magnetic resonance or directed specific puncture biopsies of the nodes or seminal vesicles can help to identify those patients unlikely to

In addition, it is extremely important that radical prostatectomy for clinical T3 cancer

In this group of patients, the incidence of organ-confined disease is around 26% to 31%. The PSA value and percentage of positive prostate biopsies may help to select men with high-

Rioja Zuazu J. et al. (38) analyzed the characteristics of the clinical Gleason 8-10 group of patients within their series of patients diagnosed with prostate cancer and treated by means of radical prostatectomy, and tried to ascertain which were the influence factors within this group, upon progression and progression free survival. They conclude, that Clinical Gleason Score 8-10 is a negative independent prognostic factor on the progression free survival, but its prognosis is better if they present a PSA prior surgery lower than 11 ng/ml and the pathological stage is a pT2. So, these kind of patients could be beneficed of RP.

Yossepowitch et al. (19) and D'Amico et al. (15) have investigated the results of RP in these patients. In all cases, very good results were seen, with a cancer- specific survival of up to

More recently, Inman and co-workers (43) described the long-term outcomes of RP with multimodal adjuvant therapy in men with PSA > 50. Systemic progression-free survival rates at 10 years were 83% and 74% for PSA 50-99 and > 100, respectively, while CSS was 87% for the whole group. These results argue for aggressive management with RP as the

Provided that the tumour is not fixed to the pelvic wall, or that there is no invasion of the urethral sphincter, RP is a reasonable first step in selected patients with a low tumour volume. In 2005, The Mayo Clinic reported a series of patients with seminal invasion, treated with RP + HT adjuvant. They had a progression free survival at 5, 10 and 15 years, of 85%, 73% and

Despite this, management decisions should be made after all treatments, and should be discussed by a multidisciplinary team, and after balancing benefits and side-effects of each therapy modality by the patient, with regard to his own individual circumstances, decision

Surgeons must understand the important anatomical and surgical principles that will allow them to improve their own technique, particularly when operating in the high-risk setting. Certain principles are important, and apply equally to open, laparoscopic and robotic

Even in a patient with a high risk of extra prostatic disease, a portion of the neurovascular

67% respectively, and a cancer specific survival of 95%, 90% and 79%.

**4.3 Optimal surgical technique for high risk cancer** 

requires sufficient surgical expertise to keep an acceptable morbidity level.

benefit from a surgical approach. (17)

**RP in High-grade PCa: Gleason score 8-10** 

grade PCa most likely to benefit from RP.

91% in 10 years in patients treated with RP.

**RP in PCa with PSA > 20** 

initial step.

**RP in cT3b-T4 N0** 

has to be taken.

surgical techniques.

bundle can often be preserved. (17)

As mentioned above, the multimodal treatment is achieving good results, and to corroborate this, several randomised studies of radiotherapy combined with androgen-deprivation therapy (ADT) versus radiotherapy alone have shown a clear advantage for combination treatment, but no trial has ever proven combined treatment to be superior to RP.
