JU INSIGHT Second Malignancies After Low-Dose-Rate Brachytherapy and Radical Prostatectomy for Prostate Cancer

By: Marie-Pier St-Laurent, MD, University of British Columbia, Vancouver, Canada; George Acland, MB, ChB, Christchurch Hospital, New Zealand; Sarah N. Hamilton, MD, British Columbia Cancer Agency Vancouver Centre, Canada, University of British Columbia, Vancouver, Canada; Jeremy Hamm, MSc, BC Cancer, Vancouver, British Columbia, Canada; Katherine Sunderland, MSc, BC Cancer, Vancouver, British Columbia, Canada; Peter C. Black, MD, University of British Columbia, Vancouver, Canada; Michael McKenzie, MD, British Columbia Cancer Agency Vancouver Centre, Canada, University of British Columbia, Vancouver, Canada; Mira Keyes, MD, British Columbia Cancer Agency Vancouver Centre, Canada, University of British Columbia, Vancouver, Canada; Stacy Miller, MD, BC Cancer—Centre for the North, Prince George, British Columbia, Canada; Martin E. Gleave, MD*, University of British Columbia, Vancouver, Canada; Scott Tyldesley, MD*, British Columbia Cancer Agency Vancouver Centre, Canada, University of British Columbia, Vancouver, Canada; *Co-senior authors | Posted on: 17 Jul 2024

St-Laurent MP, Acland G, Hamilton SN, et al. Long-term second malignancies in prostate cancer patients treated with low-dose-rate brachytherapy and radical prostatectomy. J Urol. 2024;212(1):63-73. doi:10.1097/JU.0000000000003965

Study Need and Importance

Radiotherapy (RT) and radical prostatectomy (RP) are common treatments for localized prostate cancer. Brachytherapy (BT) is a particularly effective form of RT for localized prostate cancer that is used as an alternative to RP. Any form of RT may increase the risk of secondary cancers (SCs) due to injury to DNA in normal cells.

What We Found

In a population-based study of patients treated with BT (2378) or RP (9089) with long-term follow-up, Kaplan-Meier estimates of SC at 15 years were 6.4% and 3.2%, respectively. Men treated with BT tended to be older, and after adjusting for age, smoking status, and use of RT after RP, the hazard ratio for BT vs RP was 2.1 for invasive pelvic SC (P < .001), although death from any SC was not statistically increased (hazard ratio 1.1, P = .3; Table).

Table. Cox Proportional Hazards Multivariable Analysis

Parameter	Hazard ratio	95% Confidence limits		P value
Time to pelvic second malignant neoplasia
Treatment with BT (ref = RP)	1.81	1.45	2.26	< .001
EBRT after RP (ref = none)	1.02	0.72	1.42	.9
Age at treatment (continuous)	1.04	1.03	1.06	< .001
Smoking (ref = never)^a	2.02	1.40	2.90	< .001
Time to invasive pelvic second malignant neoplasia
Treatment with BT (ref = RP)	2.13	1.61	2.83	< .001
EBRT after RP (ref = none)	0.97	0.62	1.53	.9
Age at treatment (continuous)	1.03	1.02	1.05	< .001
Smoking (ref = never)^a	1.99	1.35	2.92	< .001
Time to any second malignant neoplasia
Treatment with BT (ref = RP)	1.12	0.98	1.27	.09
EBRT after RP (ref = none)	1.09	0.92	1.28	.33
Age at treatment (continuous)	1.06	1.05	1.07	< .001
Smoking (ref = never)^a	1.84	1.58	2.15	< .001
Time since prostate cancer treatment to death from any subsequent malignancy
Treatment with BT (ref = RP)	1.10	0.92	1.31	.3
EBRT after RP (ref = none)	1.16	0.94	1.44	.2
Age at treatment (continuous)	1.05	1.04	1.06	< .001
Smoking (ref = never)^a	1.90	1.54	2.35	< .001
Abbreviations: BT, brachytherapy; EBRT, external beam radiation therapy; ref, reference; RP, radical prostatectomy. ^aWith 20 imputations for smoking status.

Limitations

It is difficult to prove a causal difference in any outcome between 2 treatments assessed in a nonrandomized study. This is due to imbalance in factors that may be associated with the risk of the event (in this case second cancers) between the 2 groups. We controlled for potential imbalance of known risk factors for second cancer (age, use of RT, and smoking status in particular) that were available in the dataset. Nonetheless, observed differences that are implied to be caused by the BT may have been caused by other factors.

Interpretation for Patient Care

In the absence of more definitive data, these findings provide some estimates for patients and their doctors of the risk of second cancer associated with the choice between RP and BT. These findings need to be considered along with other factors associated with this choice, suc