Overview
This prospective, open randomized phase III surgical trial seeks to study whether radical prostatectomy (with or without the combination of external radiation) improves prostate-cancer specific survival in comparison with primary radiation treatment and hormonal treatment among patients diagnosed with locally advanced (T3) prostate cancer. Untreated or conservatively treated locally advanced prostate cancer is associated with high mortality. Modern curative treatment for advanced solid malign tumors include surgery and/or radiation plus attempted chemotherapy if available to achieve both local control and elimination of potential micro metastases. Whereas there is evidence that surgery can cure localized prostate cancer, there are no clinical trials of multi-modal treatment of locally advanced prostate cancer that includes surgical removal of the prostate.
One potential advantage of adding prostatectomy to the treatment of LAPC is that removing the prostate enables a full pathological assessment of the tumor characteristics and thus a better estimation of the risk of recurrence. Surgical treatment could thus reduce the numbers needed to treat with chemotherapy and radiation, and thus improve quality of life after treatment. In addition, evidence indicate that residual cancer in the prostate occurs in 25% after radiation treatment (56) and surgical removal of the prostate may improve survival beyond what can be achieved by radiation and ADT. On the other hand, patients treated with surgery, radiation and hormones will experience side effects of all three treatment modalities and might fare better if radiotherapy plus hormones can provide oncological control without prior surgery.
A randomized clinical trial comparing two multimodal treatment regimens of which one includes a radical prostatectomy is therefore warranted.
Eligibility
Inclusion Criteria:
- Age ≤75, at the time of randomization
- Diagnosed histopathologically confirmed and untreated prostatic adenocarcinoma
- The general condition and mental status of patients shall permit observation in accordance with the study protocol
- Tumor stage (T, M, N):
T3 stage (as indicated by digital rectal examination or MR imaging or other validated
imaging technique) T4 tumors can be included if considered resectable/treatable on MR
imaging Significant extra-capsular tumor extension in biopsy (rare but acceptable for
inclusion) M0 (no sign of distant metastases) confirmed by bone scan or CT or MRT of axial
skeleton (at a maximum of pelvis and lumbar vertebral column) N0 stage, defined in
accordance to the RECIST guidelines as no sign of macroscopic retroperitoneal lymph-node
metastases >=1.5 cm (short axis) on CT scan, PET-CT, or MRT or more than one suspected
lymph-node metastases Presence Gleason grade pattern 4 or 5
- Signed Informed consent
Exclusion Criteria:
- Patients with a PSA value of > 100 ng/mL
- Any medical condition that, in the opinion of the investigator, might interfere with
the evaluation of the study objectives Patients with contraindications for either
prostatectomy or radiotherapy to the prostate are not eligible for the study. Most
contraindications for these treatments are relative, but in general, radiotherapy may
be precluded among patients with:
- Anorectal disease, such as fistulae, Crohn´s disease, and ulcerative colitis
- Significant obstructive lower urinary tract symptoms
- Proximal stricture of the urethrae
- Severe neurogenic bladder dysfunction
- Enlarged prostate beyond 70-90 ml
- Previous radiotherapy to the pelvic region
On the other hand, surgery may be precluded among patients with:
- Massive local tumor progression, particularly in the apical region
- Massive abdominal obesity
- Contraindications to anesthesia