Surgery Versus Radiotherapy for Locally Advanced Prostate Cancer

Prostatic Neoplasms Clinical Trial

— SPCG-15  

Official title:

Primary Radical Prostatectomy Versus Primary Radiotherapy for Locally Advanced Prostate Cancer: an Open Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02102477
• Other study ID #: SPCG-15
• Status: Recruiting
• Phase: N/A
• Start date: October 2014
• Est. completion date: December 2045

Study information

• Verified date: March 2022
• Source: Karolinska University Hospital
• Contact: Olof Akre, Prof.
• Phone: +46-8-517 700 00
• Email: olof.akre[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 2045
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Procedure:
• Prostatectomy/Surgery
Radical prostatectomy with or without adjuvant or salvage radiotherapy

Other:
• Radiotherapy with adjuvant androgen deprivation therapy
Radiotherapy with adjuvant androgen deprivation therapy

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshopsitalet Department urology	Copenhagen
Denmark	Rigshospitalet, Region h, Department Oncology	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Hospital, Department of Urology	Helsinki
Finland	Tampere University Hospital, Pihlajalinna Koskiklinikka	Tampere
Finland	Turku University Hospital	Turku
Norway	Sørlandet Hospital	Kristiansand
Norway	Oslo University Hospital, Department of radiation Therapy	Oslo
Norway	Oslo University Hospital, Department Urology	Oslo
Norway	University Hospital of North Norway	Tromsø
Norway	St. Olavs Hospital	Trondheim
Sweden	Falu Lasarett	Falun
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Helsingborgs Lasarett	Helsingborg
Sweden	Länssjukhuset Ryhov	Jönköping
Sweden	Kirurgkliniken, Blekingesjukhuset	Karlskrona
Sweden	Linköping University Hospital	Linköping
Sweden	Skåne University Hospital	Malmö
Sweden	Vrinevis Hospital	Norrköping
Sweden	Östersund Hospital	Östersund
Sweden	Capio St Göran Hospital	Stockholm
Sweden	Karolinska University Hospital	Stockholm
Sweden	Sundvalls Hospital	Sundsvall
Sweden	Umeå University Hospital	Umeå
Sweden	Uppsala Akademiska Hospital	Uppsala
Sweden	Centrallasarettet	Växjö
Sweden	Centrallasarettet Växjö Hospital	Växjö

Sponsors (1)

Lead Sponsor	Collaborator
Olof Akre

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health-care consumption	Annual Defined Daily Dose (DDD) of analgesics, prescription databases	Annually up to 10 years
Other	Health-care consumption	Annual number of days of hospitalization from patient registers	Annually up to 10 years
Primary	Cause specific survival	Cause-specific survival (CSS) will be calculated as "1-cause specific mortality. Mortality and mortality causes will be ascertained from the nationwide Cause-of-Death Register. In the absence of a functioning Cause-of-Death register, an endpoint committee of at least 2 medical doctors will determine the cause of death.	Up to 10 years
Secondary	Metastasis free survival	Composite endpoint of time to metastasis and survival	Up to 10 years
Secondary	Quality of life - general psychological, urinary, bowel and sexual health	Questionnaire-based evaluation of general psychological health, urinary health, bowel health, and sexual health.; Questions about self Questions about quality of life in the past month (scale 1 to 7; 1=no quality, 7=the best quality) Depression and anxiety (scale 1 to 7; 1=no, 7=very) Symptom Form (EPIC-26) (scale 1 to 5; 1= no problem, 5=major problem) Questions about the urinary tract Questions about sexual function Questions about bowel function Questions about prostate cancer - diagnosis and treatment Questions about prostate cancer check-ups Questions about hormone/castration therapy and its significance Questions about pain and lymph swelling	At 1,2,5 and 10 years after randomization
Secondary	Overall survival	Overall survival (OS) will be calculated as "1-overall mortality. Mortality data will be ascertained through the nationwide Cause-of-Death Register.	Up to 10 years
Secondary	Time to castration-resistant prostate cancer	Ascertained at follow-up visits	Up to 10 years
Secondary	Time to biochemical progression	Ascertained at follow-up visits	Up to 10 years
Secondary	Adverse events	Ascertained at visits	Up to 10 years
Secondary	Cardiovascular disease	Data from national PcBaSe-register (https://snd.gu.se/en/catalogue/study/ext0014), a registry where the national prostate cancer registry (NPCR, www.npcr.se) has been linked to the Swedish National Cancer Register, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register, and the Acute Myocardial Infarction Register, the Register of the Total Population, the Longitudinal Integration database for health insurance and labour market studies (LISA), the Multi-Generatioon Register and several other population-based registers.	Up to 10 years