Does the prostate status modify the clinical outcome of Radium-223 treatment in bone metastatic CRPC?

Vincenzo Serretta1, Renato Costa2, Alessandro Princiotta2, Cristina Scalici Gesolfo1, Nicola Borsellino3, Francesco Verderame4, Alessandra Morabito2, Vincenzo Tripoli2, Maria Licari2, Chiara Sanfilippo5
  • 1 Università di Palermo, Sezione di Urologia, Dipartimento di Discipline Chirurgiche Oncologiche e Stomatologiche (Palermo)
  • 2 Università di Palermo, Unità di Medicina Nucleare (Palermo)
  • 3 Ospedale Buccheri La Ferla Fatebenefratelli, Unità di Oncologia (Palermo)
  • 4 Ospedali Riuniti Villa Sofia-Cervello, Unità di Oncologia (Palermo)
  • 5 Fondazione GSTU, Statistics (Palermo)

Objective

In patients affected by bone metastatic castration-resistant prostate cancer (mCRPC) survival is improved by Radium-223 (223Ra). Even if antiandrogen hormonal therapy is maintained, the treatments for CRPC are stopped in patients undergoing 223Ra. The primary prostate tumor could progress during 223Ra treatment period, particularly if hematological toxicity, patients compliance and general status and other factors might limit the early start of further therapy.
The aim of our study was to evaluate in terms of progression, death and treatment withdrawal, the clinical impact of the presence or absence of primary tumor in patients undergoing 223Ra therapy for mCRPC.

Materials and Methods

We reviewed the clinical data of patients treated with 223Ra for symptomatic mCRPC between January 2016 and July 2017. Written informed consent was obtained. Luteinizing hormone-releasing hormone analogues were continued in all patients. Within 1 month of the planned start of the treatment Technetium-99m bone scan and total-body CT scan were performed. 223Ra was administered at the dose of 55 kBq/kg every 4 weeks for up to six injections. Patients didn't receive any other anticancer therapy during 223Ra treatment.
Patients were stratified in 2 groups in relation to the presence or absence of the primary prostate tumor.
Discontinuation of Radium-223 depended on: patient’s request, occurrence of CTCAE grade 3 or 4 neutropenia, anaemia or thrombocytopenia longer than 14 days, visceral progression or for a dose delay of more than 4 weeks. The clinical outcomes of the 2 groups were compared in terms of progression, death and treatment withdrawal due to toxicity.

Results

The clinical records of 44 consecutive patients were reviewed. Median age was 76 years and median BMI 27,2. The Gleason grade of the prostate tumor was 7 in 11 (25%), 8 in 13(29,5%) and ≥ 9 in 13 (29,5%) patients. In 28 patients (63.6%) the primary prostate tumor did not receive any local treatment while 16 (36.4%) and 5 (11.3%) patients had previously undergone radical prostatectomy or prostate radiotherapy respectively. Twenty-six (59.1%) patients had previously submitted to systemic chemotherapy.
Bone metastases were less than 6 in 9 (20,4%), between 6 and 20 in 10 (22.7%) and more than 20 in 24 (54.5%) patients. 223Ra treatment was discontinued in 17 patients (41%). Out of these 17 patients, 14 (77,7%) had their prostate, previously submitted to radiotherapy in 2 patients. Reasons of discontinuation were: toxicity, progression and other causes in 9 (20,4%), 7 (15,9%) and 1 (2,3%) patients respectively.
Twelve (27.3%) patients progressed, out of them 9 (75%) had their prostate, submitted to previous radiotherapy in 1 case only. Four of the 5 dead patients had their prostate. Although no statistical analysis was performed due to the small patients’ number, our result suggest the relevant prognostic role of the presence/absence of the primary tumor in terms of treatment completion and progression

Discussions

During 223Ra treatment, in absence of other concomitant anticancer therapy different than androgen deprivation, 78% of the treatment discontinuations and 75% of the clinical progressions were recorded among patients maintaining their prostate.

Conclusion

Our preliminary experience show that the presence of the primary prostate tumor might play a detrimental role in terms of clinical response to 223Ra.

Reference

Acknowledgments: GSTU Foundation, Palermo, Italy for the laboratory kits supply and the statistical support

Argomenti: