Clinical trial NCT02102477: Surgery Versus Radiotherapy for Locally Advanced Prostate Cancer
Official title: Primary Radical Prostatectomy Versus Primary Radiotherapy for Locally Advanced Prostate Cancer: an Open Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostatic Neoplasms
Keywords: Prostatic neoplasms
Locally advanced
Radiotherapy
Surgery
Mortality
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2014-04-03
Enrollment: 1200
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 criteria: 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

Primary outcomes:
measure: Cause specific survival
timeFrame: Up to 10 years
Secondary outcomes:
measure: Metastasis free survival
timeFrame: Up to 10 years
measure: Quality of life - general psychological, urinary, bowel and sexual health
timeFrame: At 1,2,5 and 10 years after randomization
measure: Overall survival
timeFrame: Up to 10 years
measure: Time to castration-resistant prostate cancer
timeFrame: Up to 10 years
measure: Time to biochemical progression
timeFrame: Up to 10 years
measure: Adverse events
timeFrame: Up to 10 years
measure: Cardiovascular disease
timeFrame: Up to 10 years
Other outcomes:
measure: Health-care consumption
timeFrame: Annually up to 10 years
measure: Health-care consumption
timeFrame: Annually up to 10 years
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Region h, Department Oncology
city: Copenhagen
country: Denmark
facility: Rigshopsitalet Department urology
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital, Department of Urology
city: Tampere
country: Finland
facility: Tampere University Hospital, Pihlajalinna Koskiklinikka
city: Turku
country: Finland
facility: Turku University Hospital
city: Kristiansand
country: Norway
facility: Sørlandet Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital, Department of radiation Therapy
city: Oslo
country: Norway
facility: Oslo University Hospital, Department Urology
city: Tromsø
country: Norway
facility: University Hospital of North Norway
city: Trondheim
country: Norway
facility: St. Olavs Hospital
city: Falun
country: Sweden
facility: Falu Lasarett
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Helsingborg
country: Sweden
facility: Helsingborgs Lasarett
city: Jönköping
country: Sweden
facility: Länssjukhuset Ryhov
city: Karlskrona
country: Sweden
facility: Kirurgkliniken, Blekingesjukhuset
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Malmö
country: Sweden
facility: Skåne University Hospital
city: Norrköping
country: Sweden
facility: Vrinevis Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Capio St Göran Hospital
city: Sundsvall
country: Sweden
facility: Sundvalls Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Hospital
city: Växjö
country: Sweden
facility: Centrallasarettet
city: Växjö
country: Sweden
facility: Centrallasarettet Växjö Hospital
city: Östersund
country: Sweden
facility: Östersund Hospital
Study officials:
affiliation: Sahlgrenska University Hospital, Department of Urology, SE- 413 45 Gothenburg
name: Johan Stranne, M.D ass prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Umeå University Hospital, Department of Radiation Science, SE-901 87 Umeå Sweden
name: Camilla Thellenberg Karlsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institute, Nobelsväg, SE- 171 77 Solna, Sweden
name: Eva M Johansson, R.N PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institute, Nobelsväg, SE-171 77 Solna, Sweden
name: Gunnar Steineck, M.D Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, department Urology, DK-2001-Copenhagen, Denmark
name: Klaus Brasso, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Region h, Department of Oncology, Blegdamsvej 9, DK- 2001, Copenhagen, Denmark
name: Peter M Meidahl Petersen, M.D ass prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital, Department of Urology, P.O Box 4950 Nydalen, N-0424, Oslo Norway
name: Bjørn Brennhovd, M.D ass.prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital, Department of Radiation Therapy, P.O Box 4950, N-0424, Nydalen Oslo, Norway
name: Wolfgang Lilleby, M.D ass.prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital, Department Urology,Stenbäckinkatu 9, FIN-00290 Helsinki , Finland
name: Antti Rannikko, M.D ass.prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital, Department Urology,Stenbäckinkatu 9, FIN-00290 Helsinki , Finland
name: Mauri Kouri, M.D PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital, Department Urology,Stenbäckinkatu 9, FIN-00290 Helsinki , Finland
name: Tuomas Mirtti, M.D PhD
role: PRINCIPAL_INVESTIGATOR
References: