Prostate Cancer Radical Prostatectomy A.Ariafar MD Fellowship of Urology-Oncology

Prostate cancer is the fifth most common malignancy worldwide and the second most common in men Parkin et al, 2005 Prostate cancer makes up 11.7% of new cancer cases overall, 19% in developed countries, and 5.3% in developing countries The lowest yearly incidence rates occur in Asia (1.9 cases per 100,000 in China) and the highest in North America and Scandinavia, especially in African-Americans (249 cases per 100,000) Parkin et al, 2005; American Cancer Society, 2008 Prostate cancer has been the most common noncutaneous malignancy in U.S. The estimated lifetime risk of disease is 16.72%, with a lifetime risk of death at 2.57%. American Cancer Society, 2008

Prostate cancer is rarely diagnosed in men younger than 50 years old, accounting for only 2% of all cases Jani et al, 2008. The median age at diagnosis is 68 years, with 63% diagnosed after age 65 Ries et al, 2011 Since the introduction of PSA testing, the incidence of local-regional disease has increased, whereas the incidence of metastatic disease has decreased Newcomer et al, 1997 Nonpalpable cancers (clinical stage T1c) now account for 60% to 75% of newly diagnosed disease Derweesh et al, 2004; Gallina et al, 2008 Clinical stage migration has also been associated with improvements in 5- and 10-year disease-specific survival, which for all stages combined now are 99% and 91%, respectively American Cancer Society, 2008

The Changing Face of Prostate Cancer Cooperberg et al. J Urol 2007; 178:S14

Risk stratification of surgical population over time Risk stratification of surgical population over time. Low risk: prostate-specific antigen (PSA) less than 10, and stage T1 or T2a, and biopsy Gleason score = 6 or lower. Intermediate risk: PSA 10 to 20, or stage T2b or T2c, or biopsy Gleason score = 7. High risk: PSA more than 20, or stage T3, or biopsy Gleason score = 8 or higher, or any two or more intermediate risk factors. Declining rate of extracapsular extension (resulting in increased rate of organ-confined disease) on radical prostatectomy specimens at the Cleveland Clinic, 1987-2005. Trends in pathologic stage migration with joinpoint regression analysis. Annual change: 1987 to 1992: −2.9%; 1992 to 1995: −16.9%; 1995 to 2005: −4.2%. NOCD, non–organ-confined disease.

Definitive Therapy for Localized Prostate Cancer CONSERVATIVE MANAGEMENT Active Surveillance Watchful Waiting RADICAL PROSTATECTOMY Perineal Retropubic Laparoscopic Robotic RADIATION THERAPY External Beam Radiotherapy (Three-Dimensional Conformal Radiotherapy) Brachytherapy

RADICAL PROSTATECTOMY Radical prostatectomy was the first treatment used for prostate cancer and has been performed for more than 100 years Kuchler, 1866; Young, 1905. No treatment has supplanted radical prostatectomy, and it still remains the gold standard because of the realization that hormone therapy and chemotherapy are never curative, and not all cancer cells can be eradicated consistently by radiation or other physical forms of energy, even if the tumor is contained within the prostate gland Campbell’s urology 2011 ,chapter 100

Advantage of RP The main advantage of radical prostatectomy is that when skillfully performed, it offers the possibility of cure with minimal collateral damage to surrounding tissues Han et al, 2001b; Hull et al, 2002. Further, it provides more accurate tumor staging by pathologic examination of the surgical specimen. Also, treatment failure is more readily identified, and the postoperative course is much smoother than in the past Campbell’s urology 2011 ,chapter 100

Advantage of RP Radical prostatectomy significantly reduces local progression and distant metastases and improves cancer-specific and overall survival rates compared with watchful waiting Bill-Axelson et al,2008 Patients with tumor recurrence after radical prostatectomy can be salvaged with potentially curative postoperative radiotherapy Stephenson et al, 2004b; Trock et al, 2008.

Disadvantages of RP The potential disadvantages of radical prostatectomy are the necessary hospitalization and recovery period Possibility of incomplete tumor resection, if the operation is not performed properly or if the tumor is not contained within the prostate gland Risk for erectile dysfunction and urinary incontinence Erectile dysfunction and rectal complications are less likely with nerve-sparing surgery than with radiotherapy, and good treatment options are available for both urinary incontinence and erectile dysfunction Rabbani et al, 2000; Stanford et al, 2000, Kundu et al, 2004; Sanda et al, 2008

Selection of Patients for Radical Prostatectomy An ideal candidate for radical prostatectomy is healthy and free of comorbidities that might make the operation unacceptably risky. He should have a life expectancy of at least 10 years, and his tumor should be deemed to be biologically significant and completely resectable. The generally accepted upper age limit for radical prostatectomy is about 75 years. Campbell’s urology 2011 Because imaging studies are not accurate for staging prostate cancer, preoperative clinical and pathologic parameters are often used to predict the pathologic stage and thus identify patients most likely to benefit from the operation Partin et al, 1997, 2001

Risk Assessment of Pca

Low-risk, localized PCa Patients with low-risk, localized PCa should be informed about the results of the randomized trial comparing retropubic RP versus watchful waiting in localized PCa In this study, RP reduced prostate cancer mortality and the risk of metastases in men younger than 65 years with little or no further increase in benefit 10 or more years after surgery J Natl Cancer Inst 2008 ;100(16):1144-54.

Stage T1a-T1b Pca A Swedish register-based study of 23,288 men with stage T1a-T1b showed a 10-year PCa mortality of 26.6%. Br J Cancer 2009;100(1):170-3 It is shown that the risk of disease progression of untreated T1a PCa after 5 years is only 5%,but these cancers can progress in about 50% of cases after 10-13 years In contrast, most patients with T1b tumours were expected to show disease progression after 5 years, and aggressive treatment was often warranted J Urol 1988;140(6):1340-4

Stage T1c and T2a Pca StageT1c has become the most prevalent type of PCa. In an individual patient, it is difficult to differentiate between clinically insignificant and life-threatening PCa. Most reports, however, stress that cT1c tumours are mostly significant and should not be left untreated as up to 30% of cT1c tumours are locally advanced disease at final histopathology J Urol 1997 Jan;157(1):244-50. In Stage T2a patients 35-55% of them will have disease progression after 5 years if not treated Cancer 1990;66(9):1927-32

Low risk Treatment Trends

Intermediate-risk, localized PCa Patients with intermediate-risk, localized PCa should be informed about the results of the randomized trial comparing RRP versus watchful waiting in localized PCa. In this study, RP reduced prostate cancer mortality and risk of metastases in men younger than 65 years with little or no further increase in benefit 10 or more years after surgery J Natl Cancer Inst 2008 ;100(16):1144-54. Stage T2b cancer will progress in more than 70% of patients within 5 years Urology 1990;36(6):493-8.

Oncological results of RP in organ-confined disease

High-risk localised PCa Despite the trends towards lower-risk PCa, 20-35% of patients with newly diagnosed PCa are still classified as high risk, based on either PSA > 20 ng/mL, Gleason score > 8, or an advanced clinical stage JNatl Cancer Inst 2009;101(18):1280-3 There is no consensus regarding the optimal treatment of men with high-risk Pca EAU 2011

Locally advanced PCa: cT3a Several randomized 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 Lancet 2002 :360(9327):103-6 In recent years, there has been renewed interest in surgery for locally advanced PCa, and several retrospective case-series with excellent 5-, 10- and 15-year overall survival (OS) and cancer-specific survival (CSS) rates have been published Over-staging of cT3 PCa is relatively frequent and occurs in 13-27% of cases.

High-grade PCa: Gleason score 8-10 Although most poorly differentiated tumours extend outside the prostate, the incidence of organ-confined disease is between 26% and 31%. One-third of patients with a biopsy Gleason score > 8 may in fact have a specimen Gleason score < 7 with better prognostic characteristics The biochemical recurrence-free survival after RP at 5 and 10 yr of follow-up was 51% and 39%, respectively Eur Urol 2008;53(2):253-9

PCa with PSA > 20 Yossepowitch et al. reported the results of RP as a monotherapy in men with PSA > 20 ng/mL in a cohort with mostly clinically organ-confined tumours and found a PSA failure rate of 44% and 53% at 5 and 10 years, respectively J Urol 2007;178(2):493-9 Inman and co-workers 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 Cancer 2008 ;113(7):1544-51.

Overall and cancer-specific survival rates for locally advanced prostate cancer

Very high-risk localised prostate cancer cT3b-T4 N0 Men with very high-risk PCa generally have a significant risk of disease progression and cancer-related death if left untreated There is a need for local control as well as a need to treat any microscopic metastases The optimal treatment approach will therefore often necessitate multiple modalities

A recent US study showed that patients who underwent RP (n = 72) for cT4 disease had a better survival than those who received HT alone or RT alone and comparable survival to that of men who received RT plus HT Cancer 2006 Jun;106:2603-9. Another study compared the outcomes of RP in very high-risk PCa (T3-T4 N0-1, N1, M1a) with those in localized PCa. Overall survival and CSS at 7 years were 76.69% and 90.2% in the advanced disease group and 88.4% and 99.3% in the organ-confined disease group, respectively Eur Urol 2007;51(4):922-9

Any T, N1 Most urologists are reluctant to perform RP for clinical N+ disease, or will cancel surgery if a frozen section shows lymph node invasion A recent study has shown a dramatic improvement in CSS and OS infavour of completed RP versus abandoned RP in patients who were found to be N+ at the time of surgery Eur Urol 2010 Jan 20. http://www.ncbi.nlm.nih.gov/pubmed/20106588 The combination of RP and early adjuvant hormonal treatment in N+ PCa has been shown to achieve a 10-year CSS rate of 80% J Urol 1999;161(4):1223-7; Lancet Oncol 2006 ;7(6):472-9.

Neoadjuvant hormonal treatment and RP Neoadjuvant hormonal therapy before RP does not provide a significant OS advantage over prostatectomy alone. Neoadjuvant hormonal therapy before RP does not provide a significant advantage in disease-free survival over prostatectomy alone. Neoadjuvant hormonal therapy before RP does substantially improve local pathological variables such as organ-confined rates, pathological down-staging, positive surgical margins and rate of lymph node involvement.

Complications of RP

Urinary Continence For high-volume radical prostatectomy surgeons, more than 90% of men recover complete urinary continence. The return of urinary continence is associated with the patient’s age: approximately 95% of men younger than 60 years can attain pad-free urinary continence after surgery; 85% of men older than 70 years regain continence. Campbell’s urology 2011 ,chapter 100

Erectile Function The return of erectile function after radical retropubic prostatectomy correlates with the age of the patient, preoperative potency status, extent of nerve-sparing surgery, and era of surgery. In the most favorable candidates in whom preoperative potency is normal and bilateral nerve-sparing surgery can be performed, up to 95% in their 40s, 85% in their 50s, 75% in their 60s, and 50% in their 70s can attain recovery of erections sufficient for penetration and intercourse Campbell’s urology 2011 ,chapter 100

Guidelines and recommendations for radical prostatectomy EAU 2011

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