DOES THE PRESENCE OF THE PRIMARY TUMOR MODIFY THE CLINICAL OUTCOME IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENTS SUBMITTED TO RADIUM-223 THERAPY?

• Published in: Anticancer research Vol. 38; no. 4; p. 2498
• Main Authors: Serretta, Vincenzo, Costa, Renato, Princiotta, Alessandro, Gesolfo, Cristina Scalici, Borsellino, Nicola, Verderame, Francesco, Cicero, Giuseppe, Morabito, Alessandra, Tripoli, Vincenzo, Licari, Maria, Sanfilippo, Chiara
• Format: Journal Article
• Language: English
• Published: Athens International Institute of Anticancer Research 01-04-2018
• Subjects: Androgens; Anemia; Body mass; Body mass index; Body size; Cancer; Cancer surgery; Castration; Chemotherapy; Computed tomography; Deprivation; Gonadotropin-releasing hormone; Hematology; Informed consent; Lesions; Luteinizing hormone; Median (statistics); Metastases; Metastasis; Neutropenia; Patients; Progressions; Prostate cancer; Prostatectomy; Radiation therapy; Radium; Statistical analysis; Statistics; Technetium; Technetium isotopes; Thrombocytopenia; Toxicity; Tumors
• ISSN: 0250-7005; 1791-7530

Background/Aim: Radium-223 (223Ra) improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Although anti-androgen hormonal therapy is maintained, the treatments for CRPC are usually not given in patients undergoing 223Ra. The primary prostate tumor could progress during 223Ra treatment, particularly if hematological toxicity, patient compliance, general status, and other factors might limit the early start of further therapy. The aim of our study was to evaluate the clinical impact of the presence or absence of primary tumor in terms of progression, death, and treatment withdrawal in patients with mCRPC undergoing 223Ra therapy. Materials and Methods: The clinical files of mCRPC symptomatic patients treated with 223Ra between January 2016 and July 2017 were reviewed. All patients provided written informed consent. In all patients luteinizing hormone-releasing hormone analogues therapy was maintained. Technetium-99m bone scan and total-body computed tomography (CT) scan were obtained within one month of the planned start of the treatment. The 223Ra treatment schedule consisted in the administration of 55 kBq/kg every 4 weeks for up to six injections. No other anticancer therapy was given during 223Ra treatment. Patients were stratified according to the presence or absence of the primary prostate tumor. 223Ra treatment was discontinued at patient’s request, on occurrence of CTCAE grade 3 or 4 neutropenia, anemia or thrombocytopenia lasting longer than 14 days, or due to visceral progression or a dose delay (>4 weeks). Hematological toxicity was monitored with different intervals according to the number of metastases. Clinical outcomes in terms of progression, death, and treatment withdrawal due to toxicity were analyzed according to the presence/absence of the primary tumor. Results: The clinical records files of 44 consecutive patients were reviewed. Median age was 76 years and median body mass index 27.2. The Gleason grade of the prostate tumor was 7, 8, and 9-10, in 11 (25%), 13(29.5%), and 13 (29.5%) patients, respectively. Sixteen (36.4%) patients were previously submitted to radical prostatectomy and 5 (11.3%) to prostatic radiotherapy, while in 28 (63.6%) the primary prostate tumor did not receive any local treatment. All patients had bone metastases, the number of lesions was less than 6 in 9 (20.4%), between 6 and 20 in 10 (22.7%), and more than 20 in 24 (54.5%) patients. Twenty-six (59.1%) patients had previously received systemic chemotherapy. 223Ra regimen was suspended in 17 patients (41%): for toxicity in 9 (20.4%), for progression in 7 (15.9%), and for other causes in 1 (2.3%). Fourteen of these 17 patients (77.7%) were not submitted to prostatectomy (2/14 patients previously treated previous radiotherapy). Out of 12 (27.3%) patients showing progression, 9 (75%) patients were not submitted to prostatectomy (1/9 submitted to previous radiotherapy). Five patients died, 4 of them due to their prostate. Although no statistical analysis was performed due to the small patients’ number, our results suggest the relevant prognostic role of the presence/absence of the primary tumor in terms of treatment completion and progression. Discussion and Conclusion: During 223Ra treatment, in absence of other concomitant anticancer therapies different than androgen deprivation, 78% of the treatment discontinuations and 75% of the clinical progressions were recorded among patients without prostatectomy. In our preliminary experience, the presence of the primary prostate tumor plays a detrimental role in terms of treatment completion and clinical response in 223Ra treatment. GSTU Foundation, Palermo, Italy for the laboratory kits supply and the statistical support.