ANTICANCER RESEARCH 25: 551-562 (2005) Review Prostate Cancer Therapy: Standard Management, New Options and Experimental Approaches LUTZ TROJAN, KOBA KIKNAVELIDZE, THOMAS KNOLL, PETER ALKEN and MAURICE STEPHAN MICHEL Department of Urology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany Abstract. The management of prostate cancer is one of the The established therapeutic methods include purely core tasks for urologists today. This review focuses on surgical procedures (radical prostatovesiculectomy), radio- therapeutic options for the curative and palliative treatment of therapeutic methods (external beam irradiation, prostate cancer. Within the area of urological competence, brachytherapy) and medical treatment (hormonal ablation radical prostatectomy remains the standard procedure for the and chemotherapy). Several alternative minimally-invasive curative treatment of localised prostate cancer. Recently, interest therapeutic procedures have been developed over the last in minimally-invasive procedures such as brachytherapy, few years, such as high-intensity focused ultrasound (HIFU) focused ultrasound and cryotherapy has increased considerably. and cryoablation. Nevertheless, these must be rated as Established palliative treatment strategies include hormonal experimental procedures and should be performed only in treatment schemes as the gold standard. Chemotherapeutic medical centres and in a clinical trial setting. A special type regimes are used for the hormone refractory disease. In addition of prostate carcinoma treatment is "watchful waiting". This to both the standard and new urological therapeutic options, method rejects immediate therapeutic intervention against promising experimental systemic strategies for the generalised the malignancy, such action only being taken in the case of disease are presented in this review. a progressive disease. There has been a rising incidence in prostate cancer over Radical prostatectomy the last 20 years, with the peak being reached in 1995. Prostate cancer is the second most frequent malignancy The standard method for the treatment of localised prostate among males in Western Europe and the most common cancer today is radical prostatectomy, which can be cancer in men in the United States (1, 2). Therefore, the performed as an open or a laparoscopic surgical procedure. different strategies being used to treat prostate cancer are It is usually carried out with a curative purpose in mind. In of increasing interest. Generally speaking, these are all cases, the whole prostate gland is removed. The excised divided into potentially curative procedures for localised specimen includes the proximal prostatic part of the carcinoma (T1-T2, N0, M0) and palliative procedures for urethra, some parts of the bladder neck and both seminal the treatment of locally advanced or generalised diseases. vesicles. Reconstruction of the urine passage is performed The TNM classification of the UICC, 1997 version, is used by an anastomosis between the stump of the proximal in this review. urethra and the bladder neck. Post-surgical infertility exists because both ductii deferentes are ligated. The duration of the operation depends on the surgical approach used (retropubic, perineal or lapraroscopic) and Correspondence to: Lutz Trojan M.D., Department of Urology, takes between 1.5 to 3 hours. The post-surgical University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, D- hospitalisation time in our clinic is about 7 days. The 68167 Mannheim, Germany. Tel: +49-621-3832629, Fax: +49-621- intraoperatively inserted balloon catheter is removed after 3831452, e-mail: [email protected] 7 or 14 days, depending on the operative technique chosen. Key Words: Prostate cancer, therapy, radical prostatectomy, The open surgical operation can be divided into the brachytherapy, cryotherapy, high intensity focused ultrasound, retropubic (extraperitoneal) and the perineal approach, watchful waiting, chemotherapy. depending on to the surgical incision used. Retropubic 0250-7005/2005 $2.00+.40 551 ANTICANCER RESEARCH 25: 551-562 (2005) Table I. Oncological results after radical prostatectomy from 4 studies. Study Patients Oncological follow-up (n) Stein et al. (1992) 230 10 years clinical recurrence-free survival if localised: 91%, capsular invasion: 79%, seminal vesical invasion: 58% Walsh et al. (1994) 995 10 years biochemical recurrence-free survival if localised: 85%, focal capsular invasion: 82%, extended capsular invasion: 54% Zinke et al. (1994) 3170 Cancer-specific survival 10 years: 90% 15 years: 82% Pound et al. (1997) 1623 Cancer-specific survival 5 years: 99% 10 years: 83% access offers the advantage of carrying out an intraoperative function. Apical (distal part of the prostate) preparation of lymphadenectomy if the PSA value is >10 ng/ml and/or the prostate can cause damage to the function of the cross- lymph node metastasis is suspected. Lymph node metastasis striped external sphincter, which can consequently result in (as a sign of a generalised disease) can be normally excluded incontinency problems. Significant reduction in the by the pathologist by intraoperative analysis of the frozen perioperative morbidity rate, maintenance of the post- lymph node specimen. In the case of positive lymph node surgical erectile function and urinary continence are findings, the prostate is usually not removed and therapy for provided by anatomical studies of the prostate gland and the an advanced disease such as hormonal ablation is carried pelvis that were started more than 20 years ago (6, 7). out. A generalised disease will lead, despite surgical Today, in patients with a T2a tumor stage (tumor intervention, to tumor progression. For this reason, radical confined within the prostate capsule to one lobe of the operation of such patients is regarded as overtreatment and prostate), radical prostatectomy can be carried out as a should not be performed. Today, retropubic prostatectomy nerve-sparing procedure by identifying and preserving the can be considered as the standard approach. nerves responsible for erection. The neurovascular bundles, Over recent years, PSA screening has resulted in a rising which are located at the dorsolateral part of the prostate, number of early diagnosed (and therefore small) carcinomas can be spared on one or, in a few cases, on both sides. of the prostate, where lymphatic dissemination of the cancer Before the nerve-sparing technique was introduced, can be excluded statistically by means of nomograms (3). postoperative erectile dysfunction after radical There has, therefore, been an increasing interest in the less prostatectomy was nearly 100%, but this rate has now been invasive perineal intervention, where no intraoperative significantly reduced (8). Data from our clinic show that lymphadenectomy is performed. With the perineal potency was preserved in 43 to 50% of the patients after approach, there is no need to perform a laparotomy or to one-sided nerve-sparing operation, although the actual incise the endopelvic fascia and it avoids contact with the numbers depend heavily on the preoperative potency rate. penile dorsal vein complex and any subsequent severe It should be noted that, if a biopsy in both lobes indicates bleeding from it. Reasons for not using the perineal the presence of a carcinoma, a nerve-sparing prostatectomy approach are a large prostate gland (which can cause should be avoided for oncological reasons. Because prostate technical operative problems) or any probability of lymph cancer spreads out preferentially through the perineural node metastasis. sheaths into the periprostatic tissue (9), a nerve-sparing The long natural history of well-differentiated prostate procedure increases the risk of postoperative progression of cancer in the early stages of the disease results in a long the disease, but not among appropriately selected patients temporal latency (up to 10 years) before the appearance of (10, 11). It is necessary to discover the patient’s opinion on tumor-related morbidity and mortality (4, 5). Therefore, a preserving before the final decision on the treatment patient life expectancy of at least 10 years is a pre-condition modality is made. for performing the operation. As previously mentioned, urinary incontinence is one of Post-surgical functional deficits and complications of the undesirable functional complications after radical radical prostatectomy are mainly determined by the prostatectomy. In the past, this was a significant clinical anatomical structures surrounding the prostate. There is a problem, with 15% second-grade stress incontinence and high risk of damage to the neurovascular bundles, with 3% complete incontinence (12). An analysis done by means subsequent disturbance or failure of the penile erectile of a written questionnaire distributed to the last 182 patients 552 Trojan et al: Update on Prostate Cancer Therapy operated on in our clinic revealed that only 4% of the (23). Because of PSA-screening programs, the number of patients needed more than 2 pads per day. This low patients in these three groups is rising significantly. The long incidence of postoperative incontinence can be related to doubling time of the early-stage tumor results in a low risk of advances in the operative techniques. Insufficiency of the cancer-related morbidity and mortality. Therefore, a anastomosis between the urethra and the bladder neck definitive curative therapy for these patients has to be requires prolonged