Annual Meeting Proceedings Part 1 - American Society of Clinical ...

4508 Oral Abstract Session, Sat, 3:00 PM-6:00 PM
Bilateral testicular cancer within two prospective, population-based SWENO-
TECA protocols in clinical stage I nonseminoma. Presenting Author:
Torgrim Tandstad, St. Olav’s Hospital, Trondheim, Norway
Background: Contralateral tumor (CLT) occurs in 3.5-5% in men diagnosed
with testicular cancer. The precursor lesion, ITGCNU, transforms into
invasive germ cell cancer in 50-100%. Although radiotherapy eradicates
ITGCNU effectively, mandatory biopsy of the contralateral testis to detect
ITGCNU is controversial. Whether, adjuvant chemotherapy (ACT) reduces
the incidence of bilateral cancer is also uncertain. Methods: 988 patients
with clinical stage 1 nonseminoma were included in two prospective,
population-based SWENOTECA protocols. Thirteen patients were excluded
due to previous contralateral biopsy, synchronous bilateral cancer or
protocol violations. Treatment was either adjuvant chemotherapy (n�490),
or surveillance (n�485). Contralateral testicular biopsy was recommended,
but performed only in 283 patients. In case of ITGCNU radiotherapy
to 16 Gy was recommended.The estimated cumulative incidence of
CLT was calculated using the Kaplan-Meier method. Results: With a median
follow-up of 6.3 years, twenty-nine (3.9%) patients developed CLT including
five patients with synchronous cancer. Biopsies showed ITGCNU in
3.2%. The incidence of CLT was similar following ACT, 3.7 % (11/490),
and surveillance, 3.1% (12/485), p�0.99. Biopsied patients had a risk of
developing CLT of 4.3% (9/283), and seven patients treated for CIS never
developed CLT. Unbiopsied patients had a risk of 3.0 % (14/668). The
proportion of bilateral cancers was similar in biopsy negative patients 3.6%
(7/274) and unbiopsied patients 3.0 % (14/668). Young age at orchiectomy
was a significant risk factor for metachronous cancer, HR 0.94 (CI:
0.89-0.99), p�0.04. All patients with ITGCNU were offered RT. One
irradiated patient developed CLT cancer, and one developed CLT before RT
was given. Conclusions: In this selected population ACT did not reduce the
incidence of CLT. There was a high proportion of false negative biopsies,
which might explain why biopsy negative patients had the same risk of CLT
as patients not undergoing biopsy. Young patients had the highest risk of
developing contralateral cancer, the risk of CLT decreased by 6% yearly.
4510 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
Effect of denosumab on prolonging bone-metastasis free survival (BMFS)
in men with nonmetastatic castrate-resistant prostate cancer (CRPC)
presenting with aggressive PSA kinetics. Presenting Author: Fred Saad,
University of Montreal Hospital Center, Montreal, QC, Canada
Background: Denosumab, an anti-RANK-ligand monoclonal antibody, has
been shown to prolong BMFS by a median 4.2 months and with a 15% risk
reduction vs. placebo in men with non-metastatic CRPC and baseline PSA
value � 8.0 ng/mL and/or PSA doubling time (PSADT) �10.0 months. To
determine the efficacy of denosumab in men at greatest risk for bone
metastases, we evaluated BMFS in a subset of men with PSADT �6 months
(previously reported in Smith MR, et al: J Clin Oncol. 23:2918-2925,
2005). Methods: 1,432 men with non-metastatic CRPC (baseline medians:
PSA: 12.3 ng/mL, PSADT: 5.1 months, ADT duration: 47.1 months) were
randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or
placebo. The first patient enrolled February 2006; primary analysis cut-off
was July 2010, when �660 men had developed bone metastasis or died.
The primary endpoint was BMFS (time to first bone metastasis or death
from any cause). BMFS results are presented for men with baseline PSADT
�6 months. Results: Median BMFS in the placebo group of men with
PSADT �6 months was 6.5 months shorter than for the placebo group in
the full population (18.7 months vs. 25.2 months), indicating that these
men are at particularly high risk. In this group of men with PSADT �6
months, denosumab prolonged BMFS by a median of 7.2 months and with
a 23% reduction in risk compared with placebo (Table). Conclusions:
Patients with shortened PSADT are at higher risk of developing bone
metastasis and denosumab is markedly effective at prolonging BMFS in
this subset of patients.
BMFS
median
(months)
Population
Sample
size
All patients D: 716 D: 29.5
P: 716 P: 25.2
PSADT