Prostate CancerProstate CancerRadical ProstatectomyRadical Prostatectomy

A.Ariafar MDA.Ariafar MD

Fellowship of Urology-Fellowship of Urology-OncologyOncology

Prostate cancer is the fifth most common Prostate cancer is the fifth most common malignancy worldwide and the second most malignancy worldwide and the second most common in men common in men

Parkin et al, 2005 Parkin et al, 2005

Prostate cancer makes up 11.7% of new cancer Prostate cancer makes up 11.7% of new cancer cases overall, 19% in developed countries, and 5.3% cases overall, 19% in developed countries, and 5.3% in developing countries in developing countries

The lowest yearly incidence rates occur in Asia (1.9 The lowest yearly incidence rates occur in Asia (1.9 cases per 100,000 in China) and the highest in cases per 100,000 in China) and the highest in North America and Scandinavia, especially in North America and Scandinavia, especially in African-Americans (249 cases per 100,000)African-Americans (249 cases per 100,000)

Parkin et al, 2005; American Cancer Society, 2008 Parkin et al, 2005; American Cancer Society, 2008

Prostate cancer has been the most common Prostate cancer has been the most common noncutaneous malignancy in U.S. noncutaneous malignancy in U.S.

The estimated lifetime risk of disease is 16.72%, The estimated lifetime risk of disease is 16.72%, with a lifetime risk of death at 2.57%. with a lifetime risk of death at 2.57%. American American Cancer Society, 2008 Cancer Society, 2008

Prostate cancer is rarely diagnosed in men younger Prostate cancer is rarely diagnosed in men younger than 50 years old, accounting for only 2% of all cases than 50 years old, accounting for only 2% of all cases Jani et al, 2008.Jani et al, 2008.

The median age at diagnosis is 68 years, with 63% The median age at diagnosis is 68 years, with 63% diagnosed after age 65 diagnosed after age 65 Ries et Ries et al, 2011 al, 2011

Since the introduction of PSA testing, the incidence Since the introduction of PSA testing, the incidence of local-regional disease has increased, whereas the of local-regional disease has increased, whereas the incidence of metastatic disease has decreased incidence of metastatic disease has decreased

Newcomer et al, 1997 Newcomer et al, 1997

Nonpalpable cancers (clinical stage T1c) now account Nonpalpable cancers (clinical stage T1c) now account for 60% to 75% of newly diagnosed diseasefor 60% to 75% of newly diagnosed disease

Derweesh et al, 2004; Gallina et al, Derweesh et al, 2004; Gallina et al, 20082008

Clinical stage migration has also been associated with Clinical stage migration has also been associated with improvements in 5- and 10-year disease-specific improvements in 5- and 10-year disease-specific survival, which for all stages combined now are 99% survival, which for all stages combined now are 99% and 91%, respectively and 91%, respectively American American Cancer Society, 2008Cancer Society, 2008

The Changing Face of Prostate The Changing Face of Prostate CancerCancer

Cooperberg et al. J Urol 2007; 178:S14

Risk stratification of surgical Risk stratification of surgical population over time. Low risk: population over time. Low risk: prostate-specific antigen (PSA) less prostate-specific antigen (PSA) less than 10, and stage T1 or T2a, and than 10, and stage T1 or T2a, and biopsy Gleason score = 6 or lower. biopsy Gleason score = 6 or lower. Intermediate risk: PSA 10 to 20, or Intermediate risk: PSA 10 to 20, or stage T2b or T2c, or biopsy Gleason stage T2b or T2c, or biopsy Gleason score = 7. High risk: PSA more than score = 7. High risk: PSA more than 20, or stage T3, or biopsy Gleason 20, or stage T3, or biopsy Gleason score = 8 or higher, or any two or score = 8 or higher, or any two or more intermediate risk factors. more intermediate risk factors.

Declining rate of extracapsular Declining rate of extracapsular extension (resulting in increased rate extension (resulting in increased rate of organ-confined disease) on radical of organ-confined disease) on radical prostatectomy specimens at the prostatectomy specimens at the Cleveland Clinic, 1987-2005. Trends Cleveland Clinic, 1987-2005. Trends in pathologic stage migration with in pathologic stage migration with joinpoint regression analysis. Annual joinpoint regression analysis. Annual change: 1987 to 1992: −2.9%; 1992 to change: 1987 to 1992: −2.9%; 1992 to 1995: −16.9%; 1995 to 2005: −4.2%. 1995: −16.9%; 1995 to 2005: −4.2%. NOCD, non–organ-confined disease. NOCD, non–organ-confined disease.

Definitive Therapy for Localized Definitive Therapy for Localized Prostate Cancer Prostate Cancer

CONSERVATIVE MANAGEMENTCONSERVATIVE MANAGEMENT Active Surveillance Active Surveillance Watchful WaitingWatchful Waiting

RADICAL PROSTATECTOMYRADICAL PROSTATECTOMY Perineal Perineal RetropubicRetropubic Laparoscopic Laparoscopic Robotic Robotic

RADIATION THERAPYRADIATION THERAPY External Beam Radiotherapy (Three-Dimensional External Beam Radiotherapy (Three-Dimensional

Conformal Radiotherapy)Conformal Radiotherapy) BrachytherapyBrachytherapy

RADICAL RADICAL PROSTATECTOMY PROSTATECTOMY

Radical prostatectomy was the first treatment used Radical prostatectomy was the first treatment used for prostate cancer and has been performed for for prostate cancer and has been performed for more than 100 years more than 100 years Kuchler, 1866; Young, 1905.Kuchler, 1866; Young, 1905.

No treatment has supplanted radical No treatment has supplanted radical

prostatectomy, and it still remains the prostatectomy, and it still remains the gold gold standard standard because of the realization that hormone because of the realization that hormone therapy and chemotherapy are never curative, and therapy and chemotherapy are never curative, and not all cancer cells can be eradicated consistently not all cancer cells can be eradicated consistently by radiation or other physical forms of energy, even by radiation or other physical forms of energy, even if the tumor is contained within the prostate gland if the tumor is contained within the prostate gland

Campbell’s urology Campbell’s urology 2011 ,chapter 1002011 ,chapter 100

Advantage of RPAdvantage of RP The main advantage of radical prostatectomy is The main advantage of radical prostatectomy is

that when skillfully performed, it offers the that when skillfully performed, it offers the possibility of cure with minimal collateral damage possibility of cure with minimal collateral damage to surrounding tissues to surrounding tissues

Han et al, 2001b; Han et al, 2001b; Hull et al, 2002.Hull et al, 2002.

Further, it provides more accurate tumor staging Further, it provides more accurate tumor staging by pathologic examination of the surgical by pathologic examination of the surgical specimen. specimen.

Also, treatment failure is more readily identified, Also, treatment failure is more readily identified, and the postoperative course is much smoother and the postoperative course is much smoother than in the past than in the past

Campbell’s urology Campbell’s urology 2011 ,chapter 1002011 ,chapter 100

Advantage of RPAdvantage of RP

Radical prostatectomy significantly reduces Radical prostatectomy significantly reduces local progression and distant metastases and local progression and distant metastases and improves cancer-specific and overall survival improves cancer-specific and overall survival rates compared with watchful waiting rates compared with watchful waiting

Bill-Bill-Axelson et al,2008 Axelson et al,2008

Patients with tumor recurrence after radical Patients with tumor recurrence after radical prostatectomy can be salvaged with potentially prostatectomy can be salvaged with potentially curative postoperative radiotherapy curative postoperative radiotherapy

Stephenson et al, 2004b; Stephenson et al, 2004b; Trock et al, 2008.Trock et al, 2008.

Disadvantages of RPDisadvantages of RP The potential disadvantages of radical prostatectomy The potential disadvantages of radical prostatectomy

are the necessary hospitalization and recovery periodare the necessary hospitalization and recovery period

Possibility of incomplete tumor resection, if the Possibility of incomplete tumor resection, if the

operation is not performed properly or if the tumor operation is not performed properly or if the tumor is not contained within the prostate glandis not contained within the prostate gland

Risk for erectile dysfunction and urinary Risk for erectile dysfunction and urinary incontinence incontinence

Erectile dysfunction and rectal complications are Erectile dysfunction and rectal complications are less likely with nerve-sparing surgery than with less likely with nerve-sparing surgery than with radiotherapy, and good treatment options are radiotherapy, and good treatment options are available for both urinary incontinence and erectile available for both urinary incontinence and erectile dysfunctiondysfunction

Rabbani et al, 2000; Stanford et al, 2000, Kundu et al, 2004; Sanda Rabbani et al, 2000; Stanford et al, 2000, Kundu et al, 2004; Sanda et al, 2008et al, 2008

Selection of Patients for Radical Selection of Patients for Radical Prostatectomy Prostatectomy

An ideal candidate for radical prostatectomy is An ideal candidate for radical prostatectomy is healthy and free of comorbidities that might healthy and free of comorbidities that might make the operation unacceptably risky. make the operation unacceptably risky.

He should have a life expectancy of at least 10 He should have a life expectancy of at least 10 years, and his tumor should be deemed to be years, and his tumor should be deemed to be biologically significant and completely biologically significant and completely resectable. resectable.

The generally accepted upper age limit for The generally accepted upper age limit for radical prostatectomy is about 75 years. radical prostatectomy is about 75 years. Campbell’s urology 2011 Campbell’s urology 2011

Because imaging studies are not accurate for Because imaging studies are not accurate for staging prostate cancer, preoperative clinical and staging prostate cancer, preoperative clinical and pathologic parameters are often used to predict pathologic parameters are often used to predict the pathologic stage and thus identify patients the pathologic stage and thus identify patients most likely to benefit from the operation most likely to benefit from the operation Partin et al, 1997, 2001 Partin et al, 1997, 2001

Risk Assessment of PcaRisk Assessment of Pca

Low-risk, localized PCaLow-risk, localized PCa

Patients with low-risk, localized PCa should Patients with low-risk, localized PCa should be informed about the results of the be informed about the results of the randomized trial comparing retropubic RP randomized trial comparing retropubic RP versus watchful waiting in localized PCa versus watchful waiting in localized PCa

In this study, RP reduced prostate cancer In this study, RP reduced prostate cancer mortality and the risk of metastases in men mortality and the risk of metastases in men younger than 65 years with little or no younger than 65 years with little or no further increase in benefit 10 or more years further increase in benefit 10 or more years after surgeryafter surgery

J Natl Cancer Inst J Natl Cancer Inst 2008 ;100(16):1144-54.2008 ;100(16):1144-54.

Stage T1a-T1b PcaStage T1a-T1b Pca A Swedish register-based study of 23,288 men with A Swedish register-based study of 23,288 men with

stage T1a-T1b showed a 10-year PCa mortality of 26.6%.stage T1a-T1b showed a 10-year PCa mortality of 26.6%. Br J Cancer Br J Cancer

2009;100(1):170-32009;100(1):170-3

It is shown that the risk of disease progression of It is shown that the risk of disease progression of untreated T1a PCa after 5 years is only 5%,but these untreated T1a PCa after 5 years is only 5%,but these cancers can progress in about 50% of cases after 10-13 cancers can progress in about 50% of cases after 10-13 yearsyears

In contrast, most patients with T1b tumours were In contrast, most patients with T1b tumours were expected to show disease progression after 5 years, and expected to show disease progression after 5 years, and aggressive treatment was often warrantedaggressive treatment was often warranted

J Urol J Urol 1988;140(6):1340-41988;140(6):1340-4

Stage T1c and T2a PcaStage T1c and T2a Pca StageT1c has become the most prevalent type of PCa.StageT1c has become the most prevalent type of PCa. In an individual patient, it is difficult to differentiate In an individual patient, it is difficult to differentiate

between clinically insignificant and life-threatening between clinically insignificant and life-threatening PCa. PCa.

Most reports, however, stress that cT1c tumours are Most reports, however, stress that cT1c tumours are mostly significant and should not be left untreated as mostly significant and should not be left untreated as up to 30% of cT1c tumours are locally advanced up to 30% of cT1c tumours are locally advanced disease at final histopathology disease at final histopathology J J Urol 1997 Jan;157(1):244-50.Urol 1997 Jan;157(1):244-50.

In Stage T2a patients 35-55% of them will have In Stage T2a patients 35-55% of them will have disease progression after 5 years if not treateddisease progression after 5 years if not treated

Cancer Cancer 1990;66(9):1927-321990;66(9):1927-32

Low risk Treatment Low risk Treatment TrendsTrends

Intermediate-risk, Intermediate-risk, localized PCalocalized PCa

Patients with intermediate-risk, localized PCa Patients with intermediate-risk, localized PCa should be informed about the results of the should be informed about the results of the randomized trial comparing RRP versus watchful randomized trial comparing RRP versus watchful waiting in localized PCa. waiting in localized PCa.

In this study, RP reduced prostate cancer In this study, RP reduced prostate cancer mortality and risk of metastases in men younger mortality and risk of metastases in men younger than 65 years with little or no further increase in than 65 years with little or no further increase in benefit 10 or more years after surgerybenefit 10 or more years after surgery

J Natl Cancer Inst J Natl Cancer Inst 2008 ;100(16):1144-54.2008 ;100(16):1144-54.

Stage T2b cancer will progress in more than 70% Stage T2b cancer will progress in more than 70% of patients within 5 years of patients within 5 years Urology Urology 1990;36(6):493-8.1990;36(6):493-8.

Oncological results of RP in organ-Oncological results of RP in organ-confined diseaseconfined disease

High-risk localised PCaHigh-risk localised PCa Despite the trends towards lower-risk PCa, Despite the trends towards lower-risk PCa,

20-35% of patients with newly diagnosed PCa 20-35% of patients with newly diagnosed PCa are still classified as high risk, based on are still classified as high risk, based on either PSA > 20 ng/mL, Gleason score > 8, or either PSA > 20 ng/mL, Gleason score > 8, or an advanced clinical stagean advanced clinical stage

JNatl Cancer JNatl Cancer Inst 2009;101(18):1280-3Inst 2009;101(18):1280-3

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

EAU 2011EAU 2011

Locally advanced PCa: cT3aLocally advanced PCa: cT3a Several randomized studies of radiotherapy Several randomized studies of radiotherapy

combined with androgen-deprivation therapy combined with androgen-deprivation therapy (ADT) versus radiotherapy alone have shown a (ADT) versus radiotherapy alone have shown a clear advantage for combination treatment, but clear advantage for combination treatment, but no trial has ever proven combined treatment to no trial has ever proven combined treatment to be superior to RP be superior to RP Lancet Lancet 2002 :360(9327):103-62002 :360(9327):103-6

In recent years, there has been renewed interest In recent years, there has been renewed interest in surgery for locally advanced PCa, and several in surgery for locally advanced PCa, and several retrospective case-series with excellent 5-, 10- retrospective case-series with excellent 5-, 10- and 15-year overall survival (OS) and cancer-and 15-year overall survival (OS) and cancer-specific survival (CSS) rates have been publishedspecific survival (CSS) rates have been published

Over-staging of cT3 PCa is relatively frequent Over-staging of cT3 PCa is relatively frequent and occurs in 13-27% of cases.and occurs in 13-27% of cases.

High-grade PCa: Gleason score 8-10High-grade PCa: Gleason score 8-10 Although most poorly differentiated tumours Although most poorly differentiated tumours

extend outside the prostate, the incidence of extend outside the prostate, the incidence of organ-confined disease is between 26% and 31%.organ-confined disease is between 26% and 31%.

One-third of patients with a biopsy Gleason score > One-third of patients with a biopsy Gleason score > 8 may in fact have a specimen Gleason score < 7 8 may in fact have a specimen Gleason score < 7 with better prognostic characteristicswith better prognostic characteristics

The biochemical recurrence-free survival after RP The biochemical recurrence-free survival after RP at 5 and 10 yr of follow-up was 51% and 39%, at 5 and 10 yr of follow-up was 51% and 39%, respectivelyrespectively

Eur Urol Eur Urol 2008;53(2):253-92008;53(2):253-9

PCa with PSA > 20PCa with PSA > 20 Yossepowitch et al. reported the results of RP as Yossepowitch et al. reported the results of RP as

a monotherapy in men with PSA > 20 ng/mL in a a monotherapy in men with PSA > 20 ng/mL in a cohort with mostly clinically organ-confined cohort with mostly clinically organ-confined tumours and found a PSA failure rate of 44% and tumours and found a PSA failure rate of 44% and 53% at 5 and 10 years, respectively 53% at 5 and 10 years, respectively J Urol 2007;178(2):493-9J Urol 2007;178(2):493-9

Inman and co-workers described the long-term Inman and co-workers described the long-term outcomes of RP with multimodal adjuvant outcomes of RP with multimodal adjuvant therapy in men with PSA > 50.therapy in men with PSA > 50.

Systemic progression-free survival rates at 10 Systemic progression-free survival rates at 10 years were 83% and 74% for PSA 50-99 and > years were 83% and 74% for PSA 50-99 and > 100, respectively, while CSS was 87% for the 100, respectively, while CSS was 87% for the whole groupwhole group

Cancer Cancer 2008 ;113(7):1544-51.2008 ;113(7):1544-51.

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

prostate cancer prostate cancer

Very high-risk localised Very high-risk localised prostate cancerprostate cancer

cT3b-T4 N0cT3b-T4 N0 Men with very high-risk PCa generally have Men with very high-risk PCa generally have

a significant risk of disease progression and a significant risk of disease progression and cancer-related death if left untreatedcancer-related death if left untreated

There is a need for local control as well as a There is a need for local control as well as a need to treat any microscopic metastasesneed to treat any microscopic metastases

The optimal treatment approach will The optimal treatment approach will therefore often necessitate multiple therefore often necessitate multiple modalitiesmodalities

A recent US study showed that patients who A recent US study showed that patients who underwent RP (n = 72) for cT4 disease had a better underwent RP (n = 72) for cT4 disease had a better survival than those who received HT alone or RT survival than those who received HT alone or RT alone and comparable survival to that of men who alone and comparable survival to that of men who received RT plus HTreceived RT plus HT

Cancer 2006 Cancer 2006 Jun;106:2603-9.Jun;106:2603-9.

Another study compared the outcomes of RP in very Another study compared the outcomes of RP in very high-risk PCa (T3-T4 N0-1, N1, M1a) with those in high-risk PCa (T3-T4 N0-1, N1, M1a) with those in localized PCa. Overall survival and CSS at 7 years localized PCa. Overall survival and CSS at 7 years were 76.69% and 90.2% in the advanced disease were 76.69% and 90.2% in the advanced disease group and 88.4% and 99.3% in the organ-confined group and 88.4% and 99.3% in the organ-confined disease group, respectivelydisease group, respectively

Eur Urol Eur Urol 2007;51(4):922-92007;51(4):922-9

Any T, N1Any T, N1 Most urologists are reluctant to perform RP for Most urologists are reluctant to perform RP for

clinical N+ disease, or will cancel surgery if a clinical N+ disease, or will cancel surgery if a frozen section shows lymph node invasionfrozen section shows lymph node invasion

A recent study has shown a dramatic A recent study has shown a dramatic improvement in CSS and OS infavour of improvement in CSS and OS infavour of completed RP versus abandoned RP in patients completed RP versus abandoned RP in patients who were found to be N+ at the time of surgerywho were found to be N+ at the time of surgery

Eur Urol 2010 Jan 20.Eur Urol 2010 Jan 20. http://www.ncbi.nlm.nih.gov/pubmed/20106588

The combination of RP and early adjuvant The combination of RP and early adjuvant hormonal treatment in N+ PCa has been shown hormonal treatment in N+ PCa has been shown to achieve a 10-year CSS rate of 80%to achieve a 10-year CSS rate of 80%

J Urol J Urol 1999;161(4):1223-7; 1999;161(4):1223-7;

Lancet Oncol Lancet Oncol 2006 ;7(6):472-9.2006 ;7(6):472-9.

Neoadjuvant hormonal Neoadjuvant hormonal treatment and RPtreatment and RP

Neoadjuvant hormonal therapy before RP does not Neoadjuvant hormonal therapy before RP does not provide a significant OS advantage over provide a significant OS advantage over prostatectomy alone.prostatectomy alone.

Neoadjuvant hormonal therapy before RP does not Neoadjuvant hormonal therapy before RP does not provide a significant advantage in disease-free provide a significant advantage in disease-free survival over prostatectomy alone.survival over prostatectomy alone.

Neoadjuvant hormonal therapy before RP does Neoadjuvant hormonal therapy before RP does substantially improve local pathological variables substantially improve local pathological variables such as organ-confined rates, pathological down-such as organ-confined rates, pathological down-staging, positive surgical margins and rate of staging, positive surgical margins and rate of lymph node involvement.lymph node involvement.

Complications of RPComplications of RP

Urinary ContinenceUrinary Continence For high-volume radical prostatectomy For high-volume radical prostatectomy

surgeons, more than 90% of men recover surgeons, more than 90% of men recover complete urinary continence. complete urinary continence.

The return of urinary continence is The return of urinary continence is associated with the patient’s age: associated with the patient’s age: approximately 95% of men younger than 60 approximately 95% of men younger than 60 years can attain pad-free urinary continence years can attain pad-free urinary continence after surgery; 85% of men older than 70 years after surgery; 85% of men older than 70 years regain continence. regain continence.

Campbell’s Campbell’s urology 2011 ,chapter 100urology 2011 ,chapter 100

Erectile FunctionErectile Function The return of erectile function after radical The return of erectile function after radical

retropubic prostatectomy correlates with the age retropubic prostatectomy correlates with the age of the patient, preoperative potency status, extent of the patient, preoperative potency status, extent of nerve-sparing surgery, and era of surgery.of nerve-sparing surgery, and era of surgery.

In the most favorable candidates in whom In the most favorable candidates in whom preoperative potency is normal and bilateral nerve-preoperative potency is normal and bilateral nerve-sparing surgery can be performed, up to 95% in sparing surgery can be performed, up to 95% in their 40s, 85% in their 50s, 75% in their 60s, and their 40s, 85% in their 50s, 75% in their 60s, and 50% in their 70s can attain recovery of erections 50% in their 70s can attain recovery of erections sufficient for penetration and intercoursesufficient for penetration and intercourse

Campbell’s urology Campbell’s urology 2011 ,chapter 1002011 ,chapter 100

Guidelines and Guidelines and recommendations for radical recommendations for radical

prostatectomyprostatectomy

EAU 2011

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