Boosting immune response with GM-CSF optimizes primary cryotherapy outcomes in the treatment of prostate cancer: a prospective randomized clinical trial.

OBJECTIVE: We explored the association of prostate cryotherapy and immunomodulation with granulocyte-macrophage colony-stimulating factor (GMCSF) in the generation of detectable tumor-specific T- and B-cell responses in men with prostate cancer. MATERIALS AND METHODS: A randomized pilot study of patients assigned to either cryotherapy alone (Control group) or in combination with GMCSF (Treatment group). The impact of therapy on the development of T- and B-cell responses against tumor-related antigens was studied using enzyme-linked immune absorbent spot (ELISpot) and protein microarray panels (Sematrix) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISpot values against the mean pre-cryoablation response. Student t tests between treatment and control groups at 4 weeks and 12 weeks across all the antigens were performed. RESULTS: A total of 20 patients were randomized to either control or treatment arm. At 4 weeks after cryotherapy, the treatment group demonstrated an average fold change in cancer antigen-related antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% change below mean baseline (p < 0.05). At 12 weeks, antibody response in treatment group increased to 25% above baseline, while the average of control group patients remained 9% below baseline (p < 0.05). Patients in treatment group displayed, on average, higher ELISPOT readings for the 4- and 12-week times points (527 vs 481 for PSA and 748 vs 562 for PAP). CONCLUSIONS: GMCSF appeared to broadly elevate antibodies against prostate-specific and nonspecific antigens. Prostate antigen-specific T-cell responses were more enhanced over non-prostate-specific responses, preferentially in the treatment group. Our findings suggest a possible therapeutic effect of adjuvant immunotherapy in association with cryotherapy for the treatment of prostate cancer.

The Impact of Performing a 3D Mapping Biopsy Prior to Primary Cryotherapy for the Treatment of Prostate Cancer.

OBJECTIVE: To study the implications of adding a 3D mapping biopsy (3DMB) prior to prostate cryotherapy (PCT) for the treatment of prostate cancer on the following outcomes: recurrence and biochemical failure (BCF), quality of life outcomes, and complication rates. METHODS: A retrospective analysis of patients treated with either targeted focal therapy, or subtotal CT for localized prostate cancer was performed. The cohort was stratified by patients who had only had a transrectal ultrasound-guided biopsy (TRUS) and those who had undergone 1 additional 3DMB before definitive treatment. Pre- and postprocedural Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) surveys were collected. BCF was defined using the Phoenix criteria. Patients with BCF were re-biopsied. Differences in pre/post changes in IPSS and SHIM scores were examined with Mann-Whitney U tests, binary measures with chi-square tests, and pre/post changes in PSA with t tests. A Kaplan-Meier time to BCF and recurrence analysis is presented. RESULTS: A total of 534 patients underwent PCT following TRUS only (n = 331) and TRUS with subsequent 3DMB (n = 203) between March 2007 and June 2016. No differences were observed in IPSS (P = .60) or SHIM scores drop (P = .06) between groups. PSA drop seemed more pronounced in the TRUS only biopsy group compared to the 3DMB, but again without statistical significance (P = .06). Recurrence rate and BCF were lower in the 3DMB group (P <.01). There was a higher rate of short-term complications detected in the TRUS only group (P = .02). CONCLUSION: BCF and local recurrence rates were lower among patients who underwent a confirmatory 3DMB before PCT, most likely due to better risk stratification in these patients. The addition of a 3DMB did not seem to adversely impact either rate of complications or functional outcomes.

Sequential radiofrequency ablation and surgical debulking for unresectable colorectal carcinoma: thermo-surgical ablation.

BACKGROUND AND OBJECTIVES: Despite decreasing frequency, local recurrences of unresectable colorectal cancer (CRC) remain difficult problems. These patients have few treatment options with conventional therapy. Preliminary results of sequential radiofrequency ablation (RFA) and surgical debulking (thermo-surgical ablation) suggest this technique may have benefit. METHODS: We reviewed a prospective database of patients undergoing thermo-surgical ablation for unresectable colorectal carcinoma from 2003 to 2011. RESULTS: Sixteen patients were treated with unresectable, recurrent abdomino-pelvic colorectal carcinoma: 11 in pelvis; 4 with isolated aortic/retroperitoneal disease; and 1 with pelvic and peri-adrenal/retroperitoneal disease. Eleven patients had recurrent rectal cancer and five had recurrent colon cancer. Median overall and 3-year actuarial survivals were 15 months and 24%, respectively. Median and 3-year PFS was 12 months and 19%, respectively. Three patients without disease have survived 0.75, 4.0, and 7.0 years. Two patients died at 5.0 and 5.5 years. A disease-free interval (DFI) of >24 months after initial resection was associated with longer overall survival (60 months vs. 4 months; P = 0.001). CONCLUSIONS: Thermo-surgical debulking appears to have a role in the treatment of some patients with recurrent, unresectable CRC; those patients with DFI >24 months after initial surgery benefited the most.

Combined thermal-surgical ablation of locally advanced abdominopelvic malignancies.

BACKGROUND: Treatment options for patients with inoperable primary or recurrent/metastatic abdominopelvic malignancies are limited, and these patients have short lifespan. The purpose of our study is to examine outcomes of combined open radiofrequency ablation (RFA) and surgical debulking of otherwise unresectable tumors. METHODS: Consecutive 50 patients were identified from an Institutional Review Board (IRB)-approved database undergoing ablation for unresectable abdominopelvic malignancies via conventional surgical methods in a single institution between 07/2003 and 09/2009. Patients were selected for debulking if they had a dominant mass that caused significant symptoms. RESULTS: Sixteen patients had primary tumors, and 34 presented with a recurrent/metastatic malignancy. The primary tumors were abdominopelvic sarcomas (eight patients), large desmoids (two), colorectal cancer (CRC) (two), and gastric cancer, mucinous cystic pancreatic neoplasm, gastrointestinal stromal tumor (GIST), and carcinoid (one each). The recurrent/metastatic tumors were CRCs (16 patients), abdominopelvic sarcomas (12), and GIST, prostate cancer, bladder cancer, melanoma, adrenal cancer, and pseudomyxoma peritonei recurrences (1 each). Twenty-two patients were alive and 28 died as of September 2009. Median survival for patients who died was 9.5 months and for patients who were alive was 22 months. Patients with primary tumors had 5-year survival of 18% compared with no survivors at 5 years in the recurrent/metastatic group (P = 0.002). CONCLUSIONS: Thermosurgical ablation of otherwise unresectable primary tumors and recurrent/metastatic abdominopelvic malignancies is feasible in selected cases. Patients with ablated primary tumors have a survival advantage over patients who have ablation for recurrent/metastatic disease.

Combined radiofrequency-surgical debulking of advanced abdomino-pelvic tumors.

BACKGROUND: Advanced abdomino-pelvic tumors are often unresectable using surgery alone. The current study evaluated a combination of radiofrequency (RF) ablation (RFA) and surgical debulking for such lesions. METHODS: Between July 2003 and November 2004, we treated 16 patients. Fourteen had either pelvic side wall (n = 8), sacro-iliac joint (n = 4), or vertebral (n = 2) fixation. One tumor engulfed root of mesentery, the last involved stomach-liver-vena. All patients had received prior treatment. The RF probe was placed in the center of the tumor, a 4- to 6-cm tissue core ablated, and the core curetted out or aspirated. This was repeated centrifugally out to the tumor capsule. RESULTS: Control of the target lesion for more than 6 months was achieved in 10 (62%) patients; 2 died within 3 months, and 4 had tumor progression in less than 6 months. Median survival is 18+ months. CONCLUSIONS: Combined RFA-surgical debulking was feasible and beneficial in 62%% of patients with otherwise inoperable abdomino-pelvic tumors.