Surgery Versus Radiotherapy for Locally Advanced Prostate Cancer (SPCG-15)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Procedure: Prostatectomy/Surgery; Other: Radiotherapy with adjuvant androgen deprivation therapy

• Study Type: Interventional
• Enrollment (Anticipated): 1200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olof Akre, Prof.; Phone Number: +46-8-517 700 00; Email: olof.akre@ki.se

Study Locations

• Denmark
  • Aalborg, Denmark
    • Recruiting
    • Aalborg University Hospital
    • Contact: Niels Harving, M.D.
    • Principal Investigator: Niels Harving, M.D.
    • Sub-Investigator: Mette Moe Kempel, M.D.
  • Aarhus, Denmark
    • Recruiting
    • Aarhus University Hospital
    • Contact: Lise Bentzen, M.D.
    • Principal Investigator: Lise Bentzen, M.D.
    • Sub-Investigator: Martin Mortensen, M.D.
  • Copenhagen, Denmark, DK-2001
    • Recruiting
    • Rigshospitalet, Region h, Department Oncology
    • Contact: Peter M Meidahl Petersen, M.D ass
    • Principal Investigator: Peter M Meidahl Petersen, M.D ass prof
  • Copenhagen, Denmark, SE- 2001
    • Recruiting
    • Rigshopsitalet Department urology
    • Contact: Klaus Brasso, M.D
    • Principal Investigator: Klaus Brasso, M.D
  • Herlev, Denmark
    • Recruiting
    • Herlev Hospital
    • Contact: Henrik Jacobsen, M.D.
    • Principal Investigator: Henrik Jacobsen, M.D.
    • Sub-Investigator: Henriette Lindberg, M.D.
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital
    • Contact: Steinbjørn Hansen, M.D.
    • Principal Investigator: Steinbjørn Hansen, M.D.
    • Sub-Investigator: Mads Hvid, M.D.
    • Sub-Investigator: Lars Lund, M.D.
• Finland
  • Helsinki, Finland, FIN-00290
    • Recruiting
    • Helsinki University Hospital, Department of Urology
    • Contact: Antti Rannikko, M.D ass prof
    • Principal Investigator: Antti Rannikko, M.D ass prof
    • Sub-Investigator: Mauri Kouri, M.D PhD
    • Sub-Investigator: Tuomas Mirtti, M.D PhD
  • Tampere, Finland
    • Recruiting
    • Tampere University Hospital, Pihlajalinna Koskiklinikka
    • Contact: Teuvo Tammela, M.D.
    • Principal Investigator: Teuvo Tammela, M.D.
    • Sub-Investigator: Teemu Murtola, M.D.
    • Sub-Investigator: Petri Reinikainen, M.D.
  • Turku, Finland
    • Recruiting
    • Turku University Hospital
    • Contact: Peter Boström, M.D.
    • Principal Investigator: Peter Boström, M.D.
    • Sub-Investigator: Kari Syvanen, M.D.
    • Sub-Investigator: Paula Lindholm, M.D.
• Norway
  • Kristiansand, Norway, 4604
    • Recruiting
    • Sørlandet Hospital
    • Contact: Christoph Müller, Ph.D. M.D.
    • Principal Investigator: Christoph Müller, Ph.D. M.D
    • Sub-Investigator: Carl Hammarlund, M.D.
  • Oslo, Norway, N-0424
    • Recruiting
    • Oslo University Hospital, Department of radiation Therapy
    • Contact: Wolfgang Lilleby, M.D ass prof
    • Principal Investigator: Wolfang Lilleby, M.D ass prof
  • Oslo, Norway, N-0424
    • Recruiting
    • Oslo University Hospital, Department Urology
    • Contact: Bjorn Brennhovd, M.D ass prof
    • Principal Investigator: Bjorn Brennvold, M.D ass prof
  • Tromsø, Norway
    • Recruiting
    • University Hospital of North Norway
    • Contact: Hege Sagstuen, Ph.D.
    • Principal Investigator: Hege Sagstuen, Ph.D. M.D.
    • Sub-Investigator: Tore Knutsen, M.D.
    • Sub-Investigator: Bård Soltun, M.D.
    • Sub-Investigator: Kari Margrethe Larsen, M.D.
  • Trondheim, Norway
    • Recruiting
    • St. Olavs Hospital
    • Contact: Torgrim Tandstad, Ph.D.
    • Principal Investigator: Torgrim Tandstad, M.D.
    • Sub-Investigator: Heidi Knobel, M.D.
    • Sub-Investigator: Kristin Toftaker Killingberg, M.D.
    • Sub-Investigator: Arne Solberg, M.D.
• Sweden
  • Falun, Sweden, SE 791 82
    • Recruiting
    • Falu Lasarett
    • Contact: Hampus Nugin, MD
    • Principal Investigator: Hampus Nugin, MD
  • Göteborg, Sweden, SE-413 45
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: Johan Stranne, ass prof
    • Principal Investigator: Johan Stranne, M.D ass prof
  • Helsingborg, Sweden, SE 25187
    • Recruiting
    • Helsingborgs lasarett
    • Contact: Konstantinos Lentaris, MD
    • Principal Investigator: Konstantinos Lentaris, MD
  • Jönköping, Sweden, SE 553 05
    • Recruiting
    • Länssjukhuset Ryhov
    • Principal Investigator: Anders Jönsson, MD
    • Contact: Anders Jonsson, MD
  • Karlskrona, Sweden, 371 41
    • Recruiting
    • Kirurgkliniken, Blekingesjukhuset
    • Contact: Amer Mousa Kadhem, M.D.; Phone Number: +46 455 73 10 00
    • Principal Investigator: Amer Mousa Kadhem, M.D.
  • Linköping, Sweden
    • Recruiting
    • Linkoping University Hospital
    • Contact: Per Skoglund, M.D.
    • Principal Investigator: Per Skoglund, M.D.
    • Sub-Investigator: Måns Agrup, M.D.
  • Malmö, Sweden, SE 205 02
    • Recruiting
    • Skane University Hospital
    • Contact: Anders Bjartell, MD
    • Principal Investigator: Anders Bjartell, MD
  • Norrköping, Sweden, SE 601 82
    • Terminated
    • Vrinevis Hospital
  • Stockholm, Sweden, SE 171 76
    • Recruiting
    • Karolinska University Hospital
    • Contact: Olof Akre, Prof
    • Principal Investigator: Mats Olsson, MD
  • Stockholm, Sweden
    • Recruiting
    • Capio St Göran Hospital
    • Contact: Lillemor Nygren, M.D.
    • Principal Investigator: Lillemor Nygren, M.D.
    • Sub-Investigator: Marie Hjelm-Eriksson, M.D.
  • Sundsvall, Sweden
    • Recruiting
    • Sundvalls Hospital
    • Contact: Johan Styrke, M.D.
    • Principal Investigator: Johan Styrke, M.D.
    • Sub-Investigator: Lars Beckman, M.D.
  • Umeå, Sweden, SE 901 87
    • Recruiting
    • Umea University Hospital
    • Contact: Camilla Thellenberg, M.D PhD
    • Principal Investigator: Camilla Thellenberg, M.D PhD
  • Uppsala, Sweden, SE 751 85
    • Recruiting
    • Uppsala Akademiska hospital
    • Contact: Eva Johanssson, M.D
    • Principal Investigator: Eva Johanssson, MD
  • Växjö, Sweden, SE 352 34
    • Recruiting
    • Centrallasarettet
    • Contact: Amer Elwaheidy, MD
    • Principal Investigator: Amer Elwaheidy, MD
  • Växjö, Sweden
    • Recruiting
    • Centrallasarettet Växjö Hospital
    • Contact: Amer Elwaheidy, M.D.
    • Principal Investigator: Amer Elwaheidy, M.D.
  • Östersund, Sweden, SE 831 31
    • Recruiting
    • Östersund Hospital
    • Contact: Andreas Lundgren, MD
    • Principal Investigator: Andreas Lundgren, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prostatectomy/Surgery; Patients with locally advanced prostate adenocarcinoma recieves Prostatectomy/Surgery with or without adjuvant or salvage radiotherapy	Procedure: Prostatectomy/Surgery; Radical prostatectomy with or without adjuvant or salvage radiotherapy
Active Comparator: Radiotherapy with adjuvant androgen deprivation therapy; Patients with locally advanced prostate adenocarcinoma treated with adjuvant androgen deprivation therapy	Other: Radiotherapy with adjuvant androgen deprivation therapy; Radiotherapy with adjuvant androgen deprivation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis free survival	Composite endpoint of time to metastasis and survival	Up to 10 years
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
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
Time to castration-resistant prostate cancer	Ascertained at follow-up visits	Up to 10 years
Time to biochemical progression	Ascertained at follow-up visits	Up to 10 years
Adverse events	Ascertained at visits	Up to 10 years
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-care consumption	Annual Defined Daily Dose (DDD) of analgesics, prescription databases	Annually up to 10 years
Health-care consumption	Annual number of days of hospitalization from patient registers	Annually up to 10 years

Collaborators and Investigators

• Sponsor: Olof Akre
• Investigators: Principal Investigator: Johan Stranne, M.D ass prof, Sahlgrenska University Hospital, Department of Urology, SE- 413 45 Gothenburg; Principal Investigator: Camilla Thellenberg Karlsson, MD, PhD, Umeå University Hospital, Department of Radiation Science, SE-901 87 Umeå Sweden; Principal Investigator: Eva M Johansson, R.N PhD, Karolinska Institute, Nobelsväg, SE- 171 77 Solna, Sweden; Principal Investigator: Gunnar Steineck, M.D Prof, Karolinska Institute, Nobelsväg, SE-171 77 Solna, Sweden; Principal Investigator: Klaus Brasso, M.D, Rigshospitalet, department Urology, DK-2001-Copenhagen, Denmark; Principal Investigator: Peter M Meidahl Petersen, M.D ass prof, Rigshospitalet, Region h, Department of Oncology, Blegdamsvej 9, DK- 2001, Copenhagen, Denmark; Principal Investigator: Bjørn Brennhovd, M.D ass.prof, Oslo University Hospital, Department of Urology, P.O Box 4950 Nydalen, N-0424, Oslo Norway; Principal Investigator: Wolfgang Lilleby, M.D ass.prof, Oslo University Hospital, Department of Radiation Therapy, P.O Box 4950, N-0424, Nydalen Oslo, Norway; Principal Investigator: Antti Rannikko, M.D ass.prof, Helsinki University Central Hospital, Department Urology,Stenbäckinkatu 9, FIN-00290 Helsinki , Finland; Principal Investigator: Mauri Kouri, M.D PhD, Helsinki University Central Hospital, Department Urology,Stenbäckinkatu 9, FIN-00290 Helsinki , Finland; Principal Investigator: Tuomas Mirtti, M.D PhD, Helsinki University Central Hospital, Department Urology,Stenbäckinkatu 9, FIN-00290 Helsinki , Finland

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2045

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 3, 2014

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Surgery; Radiotherapy; Mortality; Locally advanced; Prostatic neoplasms
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: SPCG-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes