BACKGROUND.: The value of presalvage cryotherapy serum PSA level in predicting biochemical failure in patients with local recurrence of prostate cancer (PCa) after radiotherapy was documented; however, little is known about the predictive value of prostate‐specific antigen (PSA) doubling time (DT) in this patient group. The purpose of the current study was to evaluate serum PSA level and PSA DT as predictors of salvage cryotherapy outcomes in patients being treated for postradiotherapy locally recurrent PCa.METHODS.: The charts of patients treated with salvage cryotherapy were retrospectively reviewed for locally recurrent PCa at the M. D. Anderson Cancer Center from January 1980 to July 2004. Patients who received neoadjuvant or adjuvant hormone therapy were excluded. We assessed pre‐ and postradiotherapy clinical data, pre‐ and postsalvage cryotherapy clinical data, and other variables. Kaplan–Meier and log rank tests were performed to assess unadjusted survival probabilities and 2‐group survival comparisons, respectively. Cox proportional hazards regression models were used to assess the effect of patient characteristics in predicting overall, disease‐specific, and biochemical failure‐free survival.RESULTS.: Forty‐nine patients met the eligibility criteria. The median age of patients at diagnosis was 66 years (58–81 years) with the initial clinical stage before radiotherapy most commonly T2 (n = 25) or T3 (n = 21). The median presalvage cryotherapy serum PSA level was 5.9 ng/mL (0.4–23.1 ng/mL) and the presalvage prostatic biopsies were frequently high grade (Gleason grade ≥8 in 51% of patients). The median postsalvage cryotherapy serum PSA level was 0.1 ng/mL (0.1‐9.5 ng/mL), and biochemical failure (defined as a serum PSA level ≥2 ng/mL above the postsalvage cryotherapy PSA nadir) occurred in 26 patients. In these 26 patients, there was a statistically significant difference between pre‐ and postsalvage cryotherapy PSA DTs (12.3 months to 5.6 months, respectively; P = .02). A presalvage cryotherapy serum PSA level >10 ng/mL (P = .002) and PSA DT ≤16 months (P = .06) were found to predict the subsequent risk of biochemical failure.CONCLUSIONS.: Presalvage PSA and PSA DT can predict biochemical failure of salvage cryotherapy, although the predictive value of PSA DT only trended toward significance. The statistically significant difference in pre‐ and postsalvage cryotherapy PSA DTs was reflective of aggressive tumor biology. Cancer 2006. © 2006 American Cancer Society.

We report contemporary outcomes of salvage cryoablation at a large number of centers which have participated in the COLD (Cryo On-Line Data) Registry. A secure online database was developed to collect data for patients undergoing prostate cryoablation. Kaplan-Meier analysis was performed with biochemical failure defined using the American Society of Therapeutic Radiology and Oncology, and the Phoenix definitions. Data from 279 patients who had undergone salvage cryoablation were entered. Average patient age was 70.0 +/- 7.1 years. Pretreatment prostate specific antigen was 7.6 +/- 8.2 ng/ml and Gleason score was 7.5 +/- 1.1 (median 7). Patients were followed for 21.6 +/- 24.9 months and 47 were followed longer than 5 years. The 5-year actuarial biochemical disease-free rates were 58.9% +/- 5.7% (American Society of Therapeutic Radiology and Oncology) and 54.5% +/- 4.9% (Phoenix). As predicted based on the preservation of some prostatic tissue, 83% +/- 3.5% of patients had a detectable prostate specific antigen 0.2 ng/ml or greater at 5 years. Positive biopsies were observed in 15 of the 46 patients (32.6%) who underwent prostate biopsy after salvage cryotherapy. The incontinence rate (requiring pad use) was 4.4%. The rectal fistula rate was 1.2% and 3.2% of patients underwent transurethral prostate resection to remove sloughed tissue. Biochemical and local control rates support the use of salvage cryoablation for localized recurrence following failed radiation therapy. Efforts to continue to minimize these complications and to improve disease control in patients with persistent cancer following definitive radiotherapy should continue.

We compared the treatment outcomes of salvage radical prostatectomy and salvage cryotherapy for patients with locally recurrent prostate cancer after initial radiation therapy. We retrospectively reviewed the medical records of patients who underwent salvage radical prostatectomy at the Mayo Clinic between 1990 and 1999, and those who underwent salvage cryotherapy at M. D. Anderson Cancer Center between 1992 and 1995. Eligibility criteria were prostate specific antigen less than 10 ng/ml, post-radiation therapy biopsy showing Gleason score 8 or less and prior radiation therapy alone without pre-salvage or post-salvage hormonal therapy. We assessed the rates of biochemical disease-free survival, disease specific survival and overall survival in each group. Biochemical failure was assessed using the 2 definitions of 1) prostate specific antigen greater than 0.4 ng/ml and 2) 2 increases above the nadir prostate specific antigen. Mean followup was 7.8 years for the salvage radical prostatectomy group and 5.5 years for the salvage cryotherapy group. Compared to salvage cryotherapy, salvage radical prostatectomy resulted in superior biochemical disease-free survival by both definitions of biochemical failure (prostate specific antigen greater than 0.4 ng/ml, salvage cryotherapy 21% vs salvage radical prostatectomy 61% at 5 years, p <0.001; 2 increases above nadir with salvage cryotherapy 42% vs salvage radical prostatectomy 66% at 5 years, p = 0.002) and in superior overall survival (at 5 years salvage cryotherapy 85% vs salvage radical prostatectomy 95%, p = 0.001). There was no significant difference in disease specific survival (at 5 years salvage cryotherapy 96% vs salvage radical prostatectomy 98%, p = 0.283). After adjusting for post-radiation therapy biopsy Gleason sum and pre-salvage treatment serum prostate specific antigen on multivariate analysis salvage radical prostatectomy remained superior to salvage cryotherapy for the end points of any increase in prostate specific antigen greater than 0.4 ng/ml (HR 0.24, p <0.0001), 2 increases in prostate specific antigen (HR 0.47, p = 0.02) and overall survival (HR 0.21, p = 0.01). Young, healthy patients with recurrent prostate cancer after radiation therapy should consider salvage radical prostatectomy as it offers superior biochemical disease-free survival and may potentially offer the best chance of cure.

BACKGROUND.: The serum prostate‐specific antigen (PSA) level after definitive treatment for prostate cancer (PC) is a powerful predictor of outcome. Occasionally, PC progression can occur despite low or undetectable PSA levels. The authors report on the clinical and pathologic characteristics of patients who experienced PC progression with undetectable or low PSA levels.METHODS.: From an electronic database of all patients with PC who were treated at The University of Texas M. D. Anderson Cancer Center between 1999 and 2004, a group of 46 patients was identified who had progression to metastatic PC detected with concomitant PSA levels from 0.1 ng/mL to 2 ng/mL. Patient charts were reviewed for tumor stage, Gleason score, pretreatment PSA level, and the presence of atypical histologic variants (ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level after treatment and the PSA level at the time metastatic PC was detected were determined. The patients were followed semiannually, and imaging studies were obtained at the discretion of treating physicians. The sites of metastasis and histologic confirmation were reported when available.RESULTS.: Twenty‐three of 46 patients underwent radical prostatectomy, 11 patients received radiation therapy, and 12 received hormone treatment as their initial form of therapy. Progression to metastatic disease with concomitant, undetectable PSA levels occurred in 10 patients, including 3 patients who had not received treatment with hormones. The sites of metastasis included bone (n = 35 patients), liver (n = 7 patients), retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and brain (n = 1 patient). Aggressive and locally advanced PC were common features in these patients: Eighty‐five percent had Gleason scores ≥7, 63% had clinical T3 or T4 tumors, and 41% had pretreatment PSA levels >10 ng/mL. Atypical histologic variants were observed in 21 patients (46%) and in 8 of 10 patients who progressed with undetectable PSA levels. In 10 patients (22%), metastasis were detected in the presence of an undetectable PSA level. Eight of those patients had small cell carcinoma. In 19 patients (41%), progression to metastasis occurred without any increase in their PSA from the nadir level. Thirty‐one patients (67%) were asymptomatic at the time metastasis was detected, and the detection of metastasis in these patients occurred only because of routine imaging studies.CONCLUSIONS.: Progression of PC may occur despite undetectable or low PSA levels. Complete physical evaluation and imaging studies may be indicated in the surveillance of patients with high‐grade, locally advanced tumors, especially when atypical histologic variants are present. Cancer 2007. © 2006 American Cancer Society.

Growing teratoma syndrome (GTS) is a rare condition among patients with non-seminomatous germ cell tumors who present with enlarging metastatic masses during appropriate systemic chemotherapy and in the context of normalized serum markers. This article reviews the current pertinent scientific literature on the diagnosis and management of GTS.