Dr. med. Dirk Manski

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Prostate Cancer: Treatment by Radical Prostatectomy

Guidelines and review literature: (EAU Guidelines, Mottet et al, 2020) (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 pathological results (less R1 and tumor volume), but it 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), immediate adjuvant (salvage) radiotherapy had been standard of care. However, the validity of the studies used for this recommendation is limited, because the control groups were irradiated too late or not at all. The alternative is active surveillance and early adjuvant radiotherapy for PSA progression (PSA >0.2 ng/ml). This avoids urogenital toxicity for those patients who do not require radiotherapy. Recent studies demonstrate comparable progression-free survival for early salvage radiotherapy (Vale et al, 2020).

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]. If the patient rejects local recurrence therapy (usually radiation therapy) or if there is relevant comorbidity, imaging is not indicated. Watchful waiting is offered and hormone therapy is initiated for symptoms, proven metastasis or in dependence of the PSA doubling time.

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. PSMA-PET is a promising option for the diagnosis of the recurrence localization for patients with a PSA >0,5 ng/ml. 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 above), radiotherapy starting with a PSA under 0.5–1 ng/ml and the administration of 66–70 Gy.

Hormone Therapy for Suspected Systemic Progression

Hormone therapy is recommended for a PSA doubling time <3–6 months or symptomatic progression. Symptom-free patients with slower PSA progression should be 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 is however unclear (Schroeder et al, 2013).

Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


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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.
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