Dr. med. Dirk Manski



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Prostate Cancer: Treatment by Radical Prostatectomy


Guidelines and review literature: (EAU Guidelines, Mottet et al, 2015) (S3-Leitlinie Prostatakarzinom der DGU) (Walsh-Campbell Urology 11th Edition).

Indications for Radical Prostatectomy (RRP)

Radical prostatectomy is indicated in patients with localized prostate cancer and a life expectancy of at least 10 years. Prostatectomy is the gold standard of curative therapy. Radical prostatectomy is the only curative method which demonstrated in a randomized trial (compared to conservative therapy) a survival benefit (Bill-Axelson et al, 2005, 2008 and 2011). In retrospective analysis of large trials, radical prostatectomy shows especially for high-risk cancer oncological advantages over radiotherapy (Boorjian et al, 2012).

Possible Surgical Techniques of Radical Prostatectomy

Radical prostatectomy can be performed with various surgical techniques, which differ primarily in the surgical access. The line of dissection is the same for all techniques. Comparative studies between the different surgical techniques are available, but they are of limited value due to the trial quality (usually non-randomized or retrospective). Talent and experience of the surgeon are more important for a good postoperative outcome than the surgical approach.

Clinical Value of Lymphadenectomy:

Standard of care is performing pelvic lymphadenectomy together with radical prostatectomy. Please see section prostate cancer staging for the bounderies of the dissection field in limited and extended lymphadenectomy. In low-risk tumors (Gleason score <7 and PSA < 10 ng/ml), the probability of lymph node metastasis is very low (< 5%), pelvic lymphadenectomy can be omitted. Some authors have the opinion that the incidence of lymph node metastases is underestimated. They demand that extended pelvic lymphadenectomy should be done, if radical prostatectomy is necessary.

Nerve-Sparing Radical Prostatectomy:

Erectile function can be preserved if the cavernous nerves are spared during prostatectomy. Despite meticulous nerve sparing, after surgery patients suffer a dramatic loss of erectile function due to irritation of the cavernous nerves. Healing of the nerve fibers lead to a slow recovery, erectile funktion improves up to 2 years after radical prostatectomy. The potency rates after surgery (for patients who were potent before surgery) are between 30–60%.

Nerve-sparing is problematic from the oncologic viewpoint: the cavernous nerves are located within the fascial shell of the prostate. It is important to select patients with a low risk of a T3 tumor on the side of the planed nerve sparing. The following preoperative risk factors minimize the risk of R1 resection due to nerve sparing: PSA below 10 ng/ml, no palpable tumor and maximum one core with Gleason 4 pattern on the corresponding side.

Oncological Results of Radical Prostatectomy:

The probability of recurrence-free survival after radical prostatectomy is between 83–29% (follow-up 10 years), depending on the clinical risk. The cancer-specific 10-year survival rate is between 99–89%, see table D’Amico risk classification for prostate cancer

.

Pathological prognostic factors: independent prognostic factors in the pathological specimen are the Gleason score, margin status, extraprostatic tumor growth, seminal vesicle infiltration, perineural invasion and the presence of lymph node metastases.

Adjuvant Therapy After Prostatectomy

Neoadjuvant Hormone Treatment Before Prostatectomy:

Several randomized trials evaluated neoadjuvant hormone therapy prior to prostatectomy and found it to be ineffective. Although neoadjuvant therapy leads to better results of pathological specimen (R1, tumor volume), but this does not correlate with an improvement in recurrence-free survival. Neoadjuvant hormone therapy is not recommended prior to prostatectomy.

Neoadjuvant Chemotherapy:

Neoadjuvant chemotherapy for advanced prostate carcinomas is not an established treatment approach. However, the feasibility and an acceptable complication rate have been demonstrated in several series.

Adjuvant Hormone Therapy in pN1 After Radical Prostatectomy:

Immediate permanent hormonal therapy is standard of care for patients with lymph node metastases. It is debatable whether an immediate adjuvant hormone treatment is necessary for patients with minimal lymph node metastases. For example, patients with only one positive lymph node (after extended lymphadenectomy) will progress in only 39%. Follow-up of PSA and delaying hormone therapy until PSA level rises is therefore an option in patients with ≤2 involved lymph nodes after extended nodal dissection. An alternative to long-term hormone therapy is intermittent hormonal therapy depending on the PSA response, especially for minimal lymph node metastases [see figure intermittent androgen deprivation].

Adjuvant Hormone Therapy Without Lymph Node Metastases (pN0):

Adjuvant hormone therapy is not indicated after radical prostatectomy without lymph node metastases and without PSA progress, even if there are relevant risk factors for recurrence present (e.g. Gleason ≥8, R1 or pT3b).

Adjuvant Radiation Therapy For Positive Margins (R1):

20–60% of patients with R1 resection (and with pN0 M0) will experience a PSA progress. If obvious incomplete resection is seen in the pathological specimen (T3, broad positive margins), adjuvant radiation therapy should be considered. The alternative is active surveillance, adjuvant radiotherapy is started if a PSA rise documents the progress. According to the current german guideline for prostate cancer (DGU 2015), adjuvant radiotherapy should be performed with pT3 N0 R1 tumor stage. In patients with pT2 N0 R1, adjuvant radiotherapy can be performed or radiotherapy is initiated with PSA progression.

Three randomized studies have studies the effect of immediate adjuvant radiotherapy after RRP versus watchful waiting: EORTC trial 22911, SWOG trial 8794 and the German ARO 96-02/AUO AP 09/95 trial. Immediate adjuvant radiotherapy reduces PSA progression. However, immediate radiation therapy increases side effects compared to radiotherapy delayed until biochemical progression. In the SWOG trial with 13 years of follow-up, a significant improvement of metastasis-free survival by 1.8 years and an improvement in overall survival by 1.9 years was shown (Thompson et al, 2009). The number needed to treat is 12 for preventing metastases and 9 for preventing death after 13 years, these numbers need to be weighed against the possible over-treatment in about 50% of cases and against the increased rate of side effects.

Biochemical Recurrence After Radical Prostatectomy

Biochemical recurrence after radical prostatectomy is defined by two consecutive rising PSA values greater than 0.2 ng/ml more than three months after prostatectomy. The reason for PSA progression is either local recurrence or distant metastases [table Probability of local or systemic recurrence for patients with rising PSA after radical prostatectomy].

Probability of local or systemic recurrence for patients with rising PSA after radical prostatectomy (Heidenreich et al., 2008).
Risk factor Local recurrence (%) Systemic recurrence (%)
Time to PSA-progress
< 1 year 7 93
1–2 years 10 90
>2 years 61 39
> 3 years 74 26
PSA doubling time 11,7 Mo 4,3 Mo
Gleason score
5–6 55 45
7 39 61
8–10 11 89
local tumor stage
≤pT2b 40 60
pT3a, R0 54 46
pT3a, R1 48 52
pT3b 16 84
pN1 7 93

Diagnosis of Biochemical Recurrence After Radical Prostatectomy

A rising PSA level is very sensitive, imaging methods such as CT, bone scan or TRUS cannot localize the cause of biochemical recurrence under PSA values of 10 ng/ml and are therefore not indicated. Before further diagnostics with regard to recurrence localization, the patient must be informed about the consequences of the diagnosis. If the patient rejects local recurrence therapy (usually radiation therapy) or if there is relevant comorbidity, further studies are not indicated. Watchful waiting is offered and hormone therapy is initiated for symptoms, proven metastasis or in dependence of the PSA doubling time.

If the patient accepts local adjuvant therapy, PSMA-PET is a promising option for the diagnosis of the recurrence localization. Furthermore, the following factors speak in favour for a local recurrence (and against distant metastases): no evidence of lymph node metastases, Gleason score below 8, postoperative PSA nadir below the detection limit, PSA progress after more than one year after prostatectomy and PSA doubling time over 10 months. For an accurate analysis of prognostic factors for a local or systemic recurrence, see table probability of local or systemic recurrence for patients with rising PSA after radical prostatectomy.

Prognosis without therapy:

The formation of clinically visible metastases takes an average of 8 years; the average time to death after metastasis formation is 5 years. Unfavorable prognostic factors are an early PSA progression, time to metastases or PSA doubling time. Patients with PSA recurrence more than two years after prostatectomy, a PSA doubling time of more than 10 months, primary Gleason score <8, no seminal bladder infiltration and no lymph node metastases have a good prognosis (Pound et al, 1999). This patient group (if age is appropriate) is well suited for watchful waiting.

Radiation Therapy for Suspected Local Recurrence:

A PSA response can be expected in 20–80% of the patients, depending on selections criteria. Predictors of a successful adjuvant radiotherapy are the consequent exclusion of patients with a high probability of distant metastases (see Diagnostics) and the administration of at least 64 Gy. Furthermore, the short-term adjuvant treatment with androgen deprivation seems to be beneficial.

Hormone Therapy for PSA Progression After Prostatectomy

Hormone therapy is recommended for a PSA doubling time <3–6 months or symptomatic local progression. Symptom-free patients with slower PSA progression should be irradiated or observed until the criteria for hormonal therapy are appropriate. Adjuvant therapy with dutasteride is an option with few side effects and helps to slow down PSA progression. The influence on overall survival however, it is unclear (Schroeder et al, 2013).









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References

Asimakopoulos, A. D.; Pereira Fraga, C. T.; Annino, F.; Pasqualetti, P.; Calado, A. A. & Mugnier, C.
Randomized comparison between laparoscopic and robot-assisted nerve-sparing radical prostatectomy.
J Sex Med, 2011, 8, 1503-1512



A. Bill-Axelson, L. Holmberg, M. Ruutu, M. Haggman, S. O. Andersson, S. Bratell, A. Spangberg, C. Busch, S. Nordling, H. Garmo, J. Palmgren, H. O. Adami, B. J. Norlen, and J. E. Johansson.
Radical prostatectomy versus watchful waiting in early prostate cancer.
N Engl J Med, 352 (19): 1977–84, 2005.

A. Bill-Axelson, L. Holmberg, F. Filén, M. Ruutu, H. Garmo, C. Busch, S. Nordling, M. Häggman, S.-O. Andersson, S. Bratell, A. Spångberg, J. Palmgren, H.-O. Adami, J.-E. Johansson, and S. P. C. G. S. N. 4.
Radical prostatectomy versus watchful waiting in localized prostate cancer: the scandinavian prostate cancer group-4 randomized trial.
J Natl Cancer Inst, 100 (16): 1144–1154, Aug 2008.
doi: rm10.1093/jnci/djn255.

Bill-Axelson, A.; Holmberg, L.; Ruutu, M.; Garmo, H.; Stark, J. R.; Busch, C.; Nordling, S.; Häggman, M.; Andersson, S.; Bratell, S.; Spångberg, A.; Palmgren, J.; Steineck, G.; Adami, H.; Johansson, J. & Investigators, S. P. C. G.
Radical prostatectomy versus watchful waiting in early prostate cancer.
N Engl J Med, 2011, 364, 1708-1717.


Boorjian, S. A.; Eastham, J. A.; Graefen, M.; Guillonneau, B.; Karnes, R. J.; Moul, J. W.; Schaeffer, E. M.; Stief, C. & Zorn, K. C.
A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes.
Eur Urol, 2012, 61, 664-675.




Coelho, R. F.; Rocco, B.; Patel, M. B.; Orvieto, M. A.; Chauhan, S.; Ficarra, V.; Melegari, S.; Palmer, K. J. & Patel, V. R.
Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a critical review of outcomes reported by high-volume centers.
J Endourol, 2010, 24, 2003-2015

Epstein u.a. 1993 EPSTEIN, J. I. ; PIZOV, G. ; WALSH, P. C.:
Correlation of pathologic findings with progression after radical retropubic prostatectomy.
In: Cancer
71 (1993), Nr. 11, S. 3582–93

Ficarra, V.; Novara, G.; Fracalanza, S.; D'Elia, C.; Secco, S.; Iafrate, M.; Cavalleri, S. & Artibani, W.
A prospective, non-randomized trial comparing robot-assisted laparoscopic and retropubic radical prostatectomy in one European institution.
BJU Int, 2009, 104, 534-539

U. Ganswindt, A. Stenzl, M. Bamberg, and C. Belka.
Adjuvant radiotherapy for patients with locally advanced prostate cancer-a new standard?
Eur Urol, 54 (3): 528–542, Sep 2008.
doi: rm10.1016/j.eururo.2008.06.059.
URL http://dx.doi.org/10.1016/j.eururo.2008.06.059.

Guazzoni, G.; Cestari, A.; Naspro, R.; Riva, M.; Centemero, A.; Zanoni, M.; Rigatti, L. & Rigatti, P.
Intra- and peri-operative outcomes comparing radical retropubic and laparoscopic radical prostatectomy: results from a prospective, randomised, single-surgeon study.
Eur Urol, 2006, 50, 98-104.


Kang, D. C.; Hardee, M. J.; Fesperman, S. F.; Stoffs, T. L. & Dahm, P.
Low quality of evidence for robot-assisted laparoscopic prostatectomy: results of a systematic review of the published literature.
Eur Urol, 2010, 57, 930-937.


Porpiglia, F.; Morra, I.; Lucci Chiarissi, M.; Manfredi, M.; Mele, F.; Grande, S.; Ragni, F.; Poggio, M. & Fiori, C.
Randomised controlled trial comparing laparoscopic and robot-assisted radical prostatectomy.
Eur Urol, 2013, 63, 606-614


N. Mottet (Chair), J. Bellmunt, E. Briers (Patient Representative), R.C.N. van den Bergh (Guidelines Associate), M. Bolla, N.J. van Casteren (Guidelines Associate), P. Cornford, S. Culine, S. Joniau, T. Lam, M.D. Mason, V. Matveev, H. van der Poel, T.H. van der Kwast, O. Rouvière, T. Wiegel
Guidelines on Prostate Cancer of the European Association of Urology (EAU), https://uroweb.org/guideline/prostate-cancer/.


Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF):
Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 3.1, 2014 AWMF Registernummer: 034/022OL, http://www.awmf.org/leitlinien/detail/ll/043-022OL.html (Zugriff am: 07.02.2016)


Wein, A. J.; Kavoussi, L. R.; Partin, A. P. & Peters, C. A.
Campbell-Walsh Urology
. Elsevier, 2015. ISBN 978-1455775675.




Schröder, F.; Bangma, C.; Angulo, J. C.; Alcaraz, A.; Colombel, M.; McNicholas, T.; Tammela, T. L.; Nandy, I. & Castro, R.
Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS).
Eur Urol, 2013, 63, 779-787.


Thompson, I. M.; Tangen, C. M.; Paradelo, J.; Lucia, M. S.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E. & Crawford, E. D.
Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial.
J Urol, 2009, 181, 956-962


Trinh, Q.; Sammon, J.; Sun, M.; Ravi, P.; Ghani, K. R.; Bianchi, M.; Jeong, W.; Shariat, S. F.; Hansen, J.; Schmitges, J.; Jeldres, C.; Rogers, C. G.; Peabody, J. O.; Montorsi, F.; Menon, M. & Karakiewicz, P. I.
Perioperative outcomes of robot-assisted radical prostatectomy compared with open radical prostatectomy: results from the nationwide inpatient sample.
Eur Urol, 2012, 61, 679-685.


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