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Prostate Cancer Recurrence After Radical Prostatectomy
important for patients with locally advanced prostate cancer because Table 3: Predictive Criteria for Local or Distant
these patients are at high risk of symptomatic progression. Disease-
Recurrence After Radical Prostatectomy
15,41
free survival of pT3 was reported to vary from 40 to 65% after 10 years
of follow-up in previous studies.
37–39
However, the incidence of men
Local Recurrence Distant Recurrence
undergoing radical prostatectomy for clinical T3 prostate cancer has
Time from RP to PSA recurrence >2 years <2 years
PSA doubling time >11 months <11 months
decreased from 25% in 1987 to 2.8% in 2001.
37–39
PSA velocity <0.75ng/ml/year >0.75ng/ml/year
Pathological stage pT3a pT3b or N+
In addition, in patients who have disease involvement in the pelvic
Gleason score of RP specimens ≤7>7
lymph nodes, the PSA-free survival rate is near 30% at five years.
40
Based
Surgical margin involvement Positive Negative
on the current literature, patients can be classified into three groups by
Lymph-node involvement No Yes
risk of progression after prostatectomy. Group 1 consists of patients Seminal vesicle involvement No Yes
who are at high risk of a low PSA recurrence-free survival (<30% at 10
RP = radical prostatectomy; PSA = prostate-specific antigen.
years); pT3b, positive lymph nodes and/or Gleason score ≥8. Group 2
consists of patients who have a moderate risk and are likely to have a external-beam radiotherapy and, for presumed distant metastasis,
good chance of high PSA recurrence-free survival (70% at 10 years); hormonal therapy. ‘Observation only’ is also one of the treatment
pT3a, negative lymph node but positive surgical margins and Gleason options regardless of the recurrence site; however, standard imaging
score ≤7. Group 3 corresponds to patients who have a low risk and are tests cannot help identify the site of recurrence until the PSA reaches
likely to have an excellent PSA recurrence-free survival (95% at 10 20ng/ml, a level at which radiotherapy can no longer be expected to be
years); Gleason score of ≤6, organ-confined or extra-prostatic extension effective. Therefore, treatment is selected mainly according to the
of the disease and negative surgical margins. pathological findings of the radical prostatectomy specimen and
the post-operative serum PSA parameters.
Discriminating Between Local and
Distant Recurrence External-beam Radiotherapy
Predictive criteria that allow clinicians to distinguish between local In the European Organisation for Research and Treatment of Cancer
and systemic recurrence have been described by Pound et al. and (EORTC) 22911 trial, 1,005 patients were randomised after radical
Jhaveri et al. (see Table 3).
15,41
Overall, 30% of patients with a prostatectomy. Patients were either under surveillance (and treated in
detectable PSA have a local recurrence, whereas 70% are suspected case of recurrence) or treated by adjuvant radiotherapy.
49
The
to have metastatic disease with or without a local recurrence. included patients were stage primary prostate adenocarcinomas and
no metastases (pN0M0) and had at least one of the following risk
Regarding a digital rectal examination (DRE), several investigators have factors: extracapsular extension, positive surgical margins or seminal
demonstrated that over 50% of patients with biopsy-proven local vesicle invasion. After a median follow-up of five years, the rate of
recurrence have no abnormalities on DRE.
42–44
The usefulness of biochemical recurrence was significantly improved in the group
transrectal ultrasound (TRUS)-guided anastomotic biopsies is also treated by radiotherapy (74 versus 52.6%).
49
One limit of this study
unclear. Several studies have shown the sensitivity of this technique to needs to be underlined: 11% of patients had a detectable
be quite poor in patients with PSA <1.0ng/ml, a level at which salvage post-operative PSA value. There was no benefit to adjuvant
radiotherapy is the most efficient.
43,45,46
As a result, since radiotherapy in pT3 patients with negative surgical margins or with a
a negative biopsy does not always rule out local recurrence and a pathological specimen Gleason score <8. Moreover, pT3b and Gleason
positive result does not always exclude the presence of metastatic score 8–10 patients are at high risk of metastatic recurrence, and the
disease, the role of anastomotic biopsies remains ambiguous. Moreover, role of exclusive adjuvant radiotherapy is questionable in this
a microscopic recurrence can be missed.
43
subgroup. In addition, adjuvant radiotherapy does not improve
metastasis-free survival or overall survival.
50
However, the same study
However, it remains difficult to accurately locate the site of demonstrated that the toxicity of adjuvant radiotherapy was low. It is
recurrence. None of the usual imaging techniques is currently recommended to use a conformational radiotherapy technique, with
accurate enough to locate a recurrence early and precisely before a dose between 60 and 66 Grays, and to wait for the recovery of good
consecutively rising PSA values. However, it is for those patients with urinary continence before starting treatment. Overall, adjuvant
low values of rising PSA (i.e. <1ng/ml) that adjuvant radiotherapy is radiotherapy improves biochemically free survival with low morbidity
most likely to be effective. A bone scintigraphy is of only limited but, considering actual follow-up, it does not enhance overall survival.
usefulness before the PSA level increases to >30ng/ml, provided that
the patient remains asymptomatic. Determining the accurate Finally, it appears that the best candidates for adjuvant pelvic
anatomical location of a biochemical recurrence is actually possible in irradiation are those with recurrence with a PSA value <2ng/ml, with
some cases, but only in those patients with a PSA level >2ng/ml and a PSA doubling time >10 months and a Gleason score <8. The
by using modern molecular imaging techniques such as positron presence of positive surgical margins is doubtlessly in favour of a
emission tomography-18-fluorodeoxyglucose (PET-F18)-choline or complementary pelvic irradiation.
51
However, it is important to keep in
immunoscintigraphy (Prostacint).
47,48
mind that almost 50% of patients with positive margins will never
undergo a biochemical relapse.
Options for Adjuvant Treatment in
Case of Recurrence Hormonal Therapy
The best way to treat PSA recurrence after radical prostatectomy may The main question is whether or not hormonal treatment needs to be
depend on the site of recurrence: local, systemic or a combination of introduced early or should be delayed. Pound et al. have
both. The treatment options for presumed local recurrence include demonstrated that the median time between biochemical recurrence
EUROPEAN UROLOGICAL REVIEW 29
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