Radium-223 treatment in CRPC & presence of Primary Tumor.

[pjoshea13]

New Italian study. Only 44 men, but ....

"The presence of the primary prostate tumor seems to play a detrimental role in mCRPC patients undergoing 223Ra treatment in absence of other concomitant anticancer therapy. On the other hand a previous RP might play a protective role."

"Discussion"

"Radium 223 has been approved for the treatment of mCRPC since 2013, nevertheless published experiences in common clinical practice remain limited [16].

"

In the Alpharadin Symptomatic Prostate Cancer Patients (ALSYMPCA) approval study, patients were randomized to 223Ra or placebo and no other concomitant antineoplas- tic drug was allowed except for LHRH analogues therapy [10]. This limitation of combo strategies has been generally adopted also for 223Ra administration in clinical practice, where more heterogeneous patients’ population is likely to be treated. In this setting, patients can receive the radio- pharmaceuticals lately and after heavy therapies of the cas- tration resistance phase: in our experience, almost the 60% of patients had a bulky disease progressed after first or second line systemic chemotherapy.

"Wong et al. [17] recently analyzed the factors that might influence in common clinical practice the outcome of 223Ra treatment in 64 patients. They found that prior che- motherapy use, more than 5 bone lesions, baseline ALP, and its response to treatment statistically impacted patients’ survival. Up to date, the selection criteria for 223Ra treat- ment are not internationally identified and the results of prospective randomized trials combining 223Ra with other therapies should be awaited before adopting such combina- tions [18].

"

It must be taken into account that the patients submitted to 223Ra treatment do not receive any antineoplastic agent different from LHRH analogues in the phase of castration resistance for a period not inferior than 6 months. Thus, the patients may suffer of heavy complications due the progres- sion of the primary tumor as hydronephrosis, renal function impairment, hematuria, and bladder outlet obstruction [19]. Moreover, the presence of the primary tumor could be responsible for seeding new metastatic growths to distant sites different than bone, in addition circulating cells can reinfiltrate the prostate promoting tumor progression [13,20].

"The hypothesis of our study is that the presence of the primary tumor might play a detrimental role in patients receiving 223Ra therapy outcomes and the concomitant treatment of the primary tumor or its absence as due to previous radical prostatectomy, might play a protective role.

"During the 6 months of 223Ra therapy, 40% of our patients interrupted the treatment due to progression or toxicity. The great majority of them harbored their untreated primary tumor. Although no difference in progression rate emerged between the 2 groups, almost all the deaths occurred among the patients with prostate, confirming a statistically significant difference in terms of cancer-specific mortality.

"A limit of our study is that quality of life and pain score were not consistently documented in patients’ records therefore these points were not included in our analysis.

The different natural history between patients who receive local therapy and progress thereafter and those with metastatic disease at first diagnosis and not receiving any local treatment, according to the current standard of care, must be considered a potential bias of our study. The higher number, albeit not statistically significant, of patients with- out previous local treatment and with more than 20 bone lesions could be responsible of the difference in cancer spe- cific survival between the 2 groups. Clearly, some of the demonstrated benefits can be attributed to selection bias; men undergoing surgery are more likely to benefit, to have a lower burden of metastatic disease, or to have robust dis- ease responses with systemic therapy that would have done well despite surgical or radiation intervention [21].

"The preliminary promising data obtained in highly selected patients should be confirmed by the results of pro- spective randomized trials. Moreover, our paper is the first dealing with the potential benefit of RP in CRPC patients undergoing 223Ra.

Specifically, patients with a relatively low tumor risk and good general health status appear to benefit the most.

Considering the small number of patients, our results do not permit any meaningful conclusion and these should be considered as preliminary ones. Nevertheless, our pilot observation may have relevant clinical implications and it could be the first step of further investigational studies."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/316...

Urol Oncol. 2019 Oct 7. pii: S1078-1439(19)30327-8. doi: 10.1016/j.urolonc.2019.08.009. [Epub ahead of print]

Radium-223 treatment in castration resistant bone metastatic prostate cancer. Should be the primary tumor always treated?

Serretta V1, Valerio MR2, Costa R3, Tripoli V3, Morabito A3, Princiotta A4, Scalici Gesolfo C4, Borsellino N5, Verderame F6, Gebbia V7, Licari M3, Sanfilippo C8; members of the GSTU Foundation.

Author information

1

Department of Surgical, Oncological and Oral Sciences, Urology Unit, University of Palermo, Italy; GSTU Foundation, Statistics, Palermo, Italy. Electronic address: [e-mail].

2

Department of Surgical, Oncological and Oral Sciences, Medical Oncology Unit, University of Palermo, Italy.

3

Nuclear Medicine Unit, University of Palermo, Italy.

4

Department of Surgical, Oncological and Oral Sciences, Urology Unit, University of Palermo, Italy.

5

Oncology Unit, "Buccheri La Ferla Fatebenefratelli" Civic Hospital, Palermo, Italy.

6

Oncology Unit, "Villa Sofia-Cervello" Civic Hospital, Palermo, Italy.

7

La Maddalena Clinic, Oncology Unit, Palermo, Italy.

8

GSTU Foundation, Statistics, Palermo, Italy.

Abstract

INTRODUCTION:

Radium-223 (223Ra) improves symptoms and survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC).

STUDY AIM:

To evaluate the impact of a previous radical prostatectomy (RP) on the outcome of 223Ra therapy in mCRPC patients. The primary prostate tumor left untreated could progress during 223Ra treatment.

MATERIALS AND METHODS:

mCRPC symptomatic patients treated with 223Ra were enrolled. Luteinizing Hormone-Releasing Hormone analogue was maintained. No other anticancer therapy was given. 223Ra was administered i.v. at the dose of 55 kBq/kg every 4 weeks for 6 cycles. Patients were stratified according to previous RP or not. Hematological toxicity was monitored. Statistical analysis of 223Ra discontinuations, progressions, and deaths were performed.

RESULTS:

Forty-four patients were enrolled, 16 (36.4%) previously received RP, 5 (11.3%) prostate radiotherapy and 23 (52.3%) maintained the primary prostate tumor after local treatment. All patients presented only bone metastases, 24 patients (54.5%) had more than 20. Twenty-six (59.1%) patients were treated after first or second line systemic chemotherapy. Treatment interruptions occurred in 14 patients (50%) with prostate and in 4 (25%) without (P = 0.04). After a median follow-up of 18 months (6-30 months), 15 (53.6%), and 7 (43.7%) progressions (P = 0.34) and 13 and 1 (6.2%) deaths (P = 0.04) occurred in patients with and without prostate respectively.

CONCLUSION:

The presence of the primary prostate tumor seems to play a detrimental role in mCRPC patients undergoing 223Ra treatment in absence of other concomitant anticancer therapy. On the other hand a previous RP might play a protective role.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

Castration resistant prostate cancer; Primary tumor; Radical prostatectomy; Radiotherapy; Radium-222

PMID: 31601517 DOI: 10.1016/j.urolonc.2019.08.009

[Fairwind]

R-223 works primarily on BONE mets..The Radium is attracted more to bones than anyplace else. It will have little effect on the primary tumor or other soft tissue mets... So it's probably true that it works better if the primary tumor is removed as there will be less tumor volume....

[pjoshea13 in reply to Fairwind]

I agree that R-223 "will have little effect on ... soft tissue mets". Owing to its similarity to calcium, R-223 is preferentially taken up by bone.

The authors state that "All patients presented only bone metastases", and that "almost all the deaths occurred among the patients with prostate".

No doubt, many have often come across the statement that most men with PCa do not die of PCa - unless they get mets. 10 year survival without mets - close to 10 year survival without PCa; 5 year survival with mets - 30%.

The authors note that "the presence of the primary tumor could be responsible for seeding new metastatic growths to distant sites different than bone", & continuation of seeding is the reason put forward by those who believe that the "Mother Ship" should be eradicated.

-Patrick

[Hidden]

Sounds like de-bulking the main tumor is good, which only seems like common sense. So why has the medical establishment resisted that after the disease has become metastatic? Are too many urologists 'too smart by half'?

[pjoshea13 in reply to Hidden]

My surgeon operated on another guy the same day. He had "less serious" cancer than me, supposedly, but the cancer had reached a lymph node so he was stapled back up. That was 15 years ago & less common these days? The poor guy woke up to find that he was lighter by a couple of lymph nodes but still harbored the mother ship.

Imagine how frustrating that must have been to all the men treated that way. The OR had been booked, the patient had been prepped & cut open. Everyone was going to get paid anyway. Etc.

My treatment was a failure that day too, since the PSA only went down to 0.3. There was cancer somewhere outside the capsule, but because it wasn't in the excised nodes I lucked out. 15 years later, I'm still here, but I wonder about that other man sometimes.

-Patrick