Onset Of Distant Metastases Research Articles

Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies

The period between "successful" treatment of localized breast cancer and the onset of distant metastasis can last many years, representing an unexploited window to eradicate disseminated disease and prevent metastases. We find that the source of recurrence-disseminated tumor cells (DTCs) -evade endogenous immunity directed against tumor neoantigens. Although DTCs downregulate major histocompatibility complex I, this does not preclude recognition by conventional Tcells. Instead, the scarcity of interactions between two relatively rare populations-DTCs and endogenous antigen-specific Tcells-underlies DTC persistence. This scarcity is overcome by any one of three immunotherapies that increase the number of tumor-specific Tcells: Tcell-based vaccination, or adoptive transfer of Tcell receptor or chimeric antigen receptor Tcells. Each approach achieves robust DTC elimination, motivating discovery of MHC-restricted and -unrestricted DTC antigens that can be targeted with Tcell-based immunotherapies to eliminate the reservoir of metastasis-initiating cells in patients.

Investigation of distant metastasis occurrence rates with different treatments: A comparison of superselective intra‐arterial chemoradiotherapy and surgery

AbstractControl of distant metastasis is an important factor in improving treatment outcomes for oral cancer. Superselective intra‐arterial chemoradiotherapy (SSIACRT) has been reported to be effective for preservation of form and function, thus enabling a satisfactory outcome. However, there have also been reports of a high frequency of distant metastases with SSIACRT. The present study therefore aimed to clarify whether treatment method has any relationship with the onset of distant metastases. Of a total of 384 cases of oral cancer, 270 underwent surgery, 44 underwent surgery followed by radiotherapy, and 70 underwent SSIACRT, and distant metastases occurred in 42 cases. On multivariate analysis, only N classification was a significant risk factor (P = .0001, odds ratio = 1.848). This confirmed that the only risk factor for distant metastases is lymph node metastasis, there is no relationship to treatment method, and there are no grounds to say that SSIACRT promotes distant metastases.

Results of surgical and radiotherapeutic treatment of adenoid cystic carcinoma of the salivary glands

Surgical treatment in patients with rare adenoid cystic carcinoma (ACC) of the salivary glands is considered to be the state of the art. With respect to an additional radiotherapy there are different approaches regarding the type of radiotherapy and timing. In this study the overall survival and recurrence-free survival in 52individuals with salivary gland ACC who were treated at the University Hospital in Essen and received irradiation with fast neutrons and photons (mixed beam technique) either A) immediately following surgical treatment or B) only after the appearance of local recurrence were compared. GroupA (n = 28, first diagnosis, FD September 1991-September 2009) received adjuvant radiotherapy immediately postoperative, groupB (n = 24, FD June 1979-November 2001) underwent primarily surgical tumor resection according to the treatment regimen at that time and were irradiated only on the appearance of a local recurrence. In comparison to group B, patients in groupA showed a lower recurrence rate and a significantly longer local relapse-free survival. GroupB, however, showed a significantly higher overall survival. The frequency of distant metastasis occurred equally in both groups but the onset of distant metastasis was significantly earlier in groupA. In general, overall survival was negatively influenced by distant metastasis. The local recurrence rate was very high after primary surgical treatment only. The immediate adjuvant high-linear energy transfer (LET) radiotherapy reduced the local recurrence rates. Irradiation after the appearance of a recurrence had a positive influence on overall survival. Overall, definitive high-LET radiotherapy in the mixed beam technique enabled high local control rates both primarily postoperative and also locoregional recurrences.

Abstract OT3-01-02: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study

Abstract Introduction Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients with negative SLNs without jeopardizing survival or regional control. International guidelines keep recommending ALND in the presence of positive (+) SLNs. However SLN is the only site of axillary metastasis (MTS) in many cases (60%). Retrospective studies have also shown a low risk of locoregional relapse in patients with SLNs+ not receiving ALND.This latter finding was recently confirmed in a randomized trial comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+. However the observation of both similar relapse rate and survival in the 2 arms and the conclusion of a non-inferiority of SLNB compared to ALND require cautiousness because of some study limitations: premature enrollment cessation due to death rate lower than expected, short follow-up (6 years), small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (>90%) which irradiates the breast but also the I° axillary level, thereby contributing to the low rate of regional relapse in the SLNB arm due to lymph node sterilization. Consequently further randomized trials with more precise selection criteria based on homogeneous clinico-pathological features and with longer follow-up are needed to confirm that performing only SLNB does not affect survival or relapse risk in patients with 1-2 SLNs+. Materials and Methods Primary and secondary aims of the present 2-arm randomized trial are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse, respectively, thus evaluating whether SLNB is or is not inferior to ALND. Patients receive either conservative surgery or mastectomy and radiotherapy. They all undergo intraoperative SLNB and SLN evaluation, and are randomly assigned to either further dissection of level I-II axillary lymph nodes (standard ALND arm) or absence of any axillary surgery (experimental SLNB arm). According to International Guidelines post-surgery treatments. Eligibility criteria are: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 SLNs presenting macroMTS at intraoperative or definitive histological evaluation; no distant MTS; no neoadjuvant therapy; no previous invasive BC, signed informed consent. Exclusion criteria are: in situ, inflammatory, contralateral BC; presence of only microMTS in the SLN+; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. Follow-up controls foresee: clinical examination every 6 months for 5 years and yearly thereafter; annual mammography and breast echography; annual axillary echography for patients in the SLNB arm; additional laboratory and instrumental surveys in case of suspected onset of distant MTS. The primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and to locoregional (ipsilateral breast or axillary, internal mammary or sopraclaveolar lymph nodes) disease recurrence. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Citation Format: Corrado Tinterri, Emilia Marrazzo, Federico Frusone, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-02.

P2.16-19 Feasibility and Outcomes of Radiofrequency Ablation as Salvage Modality After Hypofractionated Radiation/SBRT for Early NSCLC

Local recurrences after radiotherapy (RT) for early non-small cell lung cancers (NSCLC) may be amenable to curative treatments. One such modality is Radio Frequency Ablation (RFA). There is paucity of data about outcomes after RFA salvage. We aim to evaluate the feasibility and outcomes of RFA when used as salvage therapy after hypo-fractionated radiation for early NSCLC. We retrospectively reviewed consecutive early NSCLC patients treated with SBRT or hypo-fractionated radiation followed by RFA salvage in an ethics board approved study. RFAs were performed using CT guidance and under general anesthesia using LeVeenTM needle. Its immediate and follow up complications were assessed. The end points of interest were local recurrence free survival (LRFS), distant relapse free survival (DRFS) and overall survival (OS). The end points were compared by the tumour size and Positron Emission Tomography (PET) maximum Standardized Uptake Value (SUVmax) 20 individuals with 21 tumours were treated with salvage RFA after RT for early tumours between 2005 and 2017. The median age was 76 years(52-94). Initial treatment was SBRT in 55%(11/20) tumours. 55%(11) tumours were adenocarcinomas, 25%(5) were squamous and 20%(4) were NSCLC- not otherwise specified. The median tumour size (long axis diameter) was 31.5mms. PET was available for 16 tumours and the median SUVmax was 6.15. The median interval since prior radiation was 24 months(8-56). The procedure was well tolerated. One individual developed pneumothorax requiring pigtail catheter drainage. The median hospitalization period was 1 day. One procedure was aborted midway due to lancinating ipsilateral arm pain. Two patients required 3 and 5 days of hospitalization respectively because of post-procedural pain. Chronically, one individual developed tissue necrosis syndrome, one individual developed hydropneumothorax and one individual developed dysphonia. The median LRFS was 31.8 months. When stratified by ≤ or >30 mms, there was no statistically significant difference in mean LRFS, but a trend was noted. Onset of distant metastases was slightly earlier in larger tumors but not statistically significant. The median overall survival for tumours ≤ or >30 mms was 42.8 months and 17.4 months respectively (p-0.015). THE LRFS was 27.7 and 60.45 months (p-0.29), DMFS was 27.8 and 54.7 months (p-0.11) for patients with PET SUV >5 and ≤5 respectively . RFA is an effective and feasible salvage modality in early NSCLC after radiation. This study is limited by its retrospective nature and limited numbers. A larger prospective analysis will help ascertain its role.

Clinical and prognostic role of detection timing of distant metastases in patients with differentiated thyroid cancer.

Distant metastases (DM) from DTC occur in 5-25% of cases and are correlated to lower survival; the prognostic significance of the temporal onset of DM is unclear. Our aim was to retrospectively analyze the prevalence of DM and to assess the prognostic role of the timing of manifestation of DM regarding the outcome. We included 174 patients (mean age 64 years). According to the time of manifestation, DM were divided in two groups: synchronous DM (SDM, n = 108) defined as metastases present at initial diagnosis and metachronous DM (MDM, n = 66) as diagnosed during follow-up. SDM were further sub grouped in pre-RAIT when diagnosed during pre-surgery work-up (n = 35) and baseline-RAIT when detected by first whole body scan after RAIT (n = 73). Disease-specific survival (DSS) was analyzed using the Kaplan-Meier method. Total RAI activities and number of treatments were significantly higher in MDM, also loss of RAI avidity was more frequent in MDM. Forty-four patients died during follow-up, of which 41 were DTC-related deaths, 5-year and 10-year DSS were 80% and 56%. On univariate analysis MDM had significantly shorter DSS; also histotype and RAI avidity were significant risk factors of impaired survival. On multivariate analysis, only loss of RAI avidity remained as independent negative predictor (p = 0.043). Considering SDM, DSS was significantly shorter in pre-RAIT group than baseline-RAIT (p = 0.004). Instead there was no significant difference between pre-RAIT-SDM and MDM in survival outcome (p = 0.875). In DTC with DM, loss of RAI uptake has an important role in survival. No significant difference in survival outcome was discovered between SDM and MDM; but, among SDM, pre-RAIT had significant shorter DSS than baseline-RAIT.

Rapid Nanophotonics Assay for Head and Neck Cancer Diagnosis

Efficient and timely diagnosis of head and neck squamous cell carcinoma (HNSCC) is a critical challenge, particularly in low and middle income countries. These regions, which are expected to witness a drastic increase in HNSCC rates, are ill-prepared to handle the diagnostic burden due to limited resources, especially the low ratio of pathologists per population, resulting in delayed diagnosis and treatment. Here, we demonstrate the potential of an alternative diagnostic method as a low-cost, resource-efficient alternative to histopathological analysis. Our novel technology employs unique surface-enhanced Raman scattering (SERS) “nanorattles” targeting cytokeratin nucleic acid biomarkers specific for HNSCC. In this first study using SERS diagnostics for head and neck cancers, we tested the diagnostic accuracy of our assay using patient tissue samples. In a blinded trial, our technique demonstrated a sensitivity of 100% and specificity of 89%, supporting its use as a useful alternative to histopathological diagnosis. The implications of our method are vast and significant in the setting of global health. Our method can provide a rapid diagnosis, allowing for earlier treatment before the onset of distant metastases. In comparison to histopathology, which can take several months in remote limited-resources regions, our method provides a diagnosis within a few hours.

Clinical outcomes following biochemical recurrence among patients with Gleason score 9-10 prostate adenocarcinoma.

102 Background: Patients with Gleason score (GS) 9-10 prostate cancer (PCa) have a high risk of early biochemical recurrence (BCR). Salvage therapy options differ depending on the upfront management strategy. Patients who received upfront surgery (RP) may be curable with salvage external beam radiation therapy (EBRT). However those who underwent EBRT or EBRT with a brachytherapy boost (EBRT+BT) are less likely to receive local salvage therapy and are commonly treated with androgen deprivation therapy (ADT). In this study, we examine the risk of distant metastases (DM) and prostate-cancer specific mortality (PCSM) among patients with GS 9-10 PCa who had BCR following RP, EBRT, or EBRT+BT. Methods: 712 patients with GS 9-10 PCa treated between 2000-2013 at 12 institutions who had BCR were included (346 RP, 282 EBRT, 84 EBRT+BT). Time to DM and PCSM were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated using age, T-stage, PSA, and GS. Results: In patients who had a BCR, incidence rates of DM and PCSM after RP were 40% and 28%. Rates after EBRT were 60% and 46% and after EBRT+BT were 49% and 31%. Median times to DM and PCSM were 3.5 and 4.9 years after RP, 3.7 and 5.1 years after EBRT, and 3.3 and 6.8 years after EBRT+BT. The rates of local salvage RT and systemic salvage therapy among RP patients were 38% and 59%, respectively. Local and systemic salvage rates were 5% and 31% for EBRT patients and 5% and 28% for EBRT+BT patients. EBRT patients had a shorter time interval to DM compared with RP (HR 1.4, p = .02) and EBRT+BT (HR 1.9, p < .01). EBRT patients also had a shorter time interval to PCSM compared with RP (HR 1.5, p = .02). Conclusions: Among patients with GS 9-10 PCa who experience BCR after definitive management, those treated with EBRT have a shorter time interval to DM and PCSM compared with RP and EBRT+BT. While this analysis is confounded by the differential thresholds for diagnosing a BCR after different modalities, it does suggest that outcomes following BCR after EBRT+BT and RP are similar. It also suggests that extreme dose escalation delays the onset of DM and PCSM even after BCR, when compared with conventionally-dosed EBRT alone.

Abstract 4851: NOTCH signaling promotes metastatic seeding and growth of human breast cancer cells

Abstract Background: NOTCH oncogenic signaling induces epithelial-to-mesenchymal transition (EMT) and tumor stemness that play a critical role in driving tumor progression. Following interaction of NOTCH receptors (NOTCH 1, 2, 3, and 4) with their ligands (DELTA-LIKE 1, 3, 4 and JAGGED 1, 2), γ- secretase complex performs an intra-membrane cleavage releasing the NOTCH intracellular domain (NNICD). NNICD translocates to the nucleus and induces the expression of HEY1 and HES1 transcription factors that in turn orchestrate NOTCH-mediated EMT and stemness reprogramming. Materials and Methods: Parental MCF-7 and unique metastatic MCF-7RAF-1 xenografts with constitutively active MAPK signaling (D’Assoro et al., Oncogene 2014: 33:599-610) were used to define the extent to which increased expression of NOTCH signaling was linked to distant metastases. SKY analysis was performed to assess the grade of chromosomal instability (CIN) in tumor xenografts. Stemness activity was assessed by culturing breast cancer cells under non-adherent conditions to generate mammospheres. Expression of CD24 luminal marker was characterized by FACS analysis and immunofluorescence. Global transcriptome analysis was performed using Affymetrix® microarray. Highly invasive MDA-MB 231 breast cancer cells were used to perform a tail vein cancer cell-seeding assay. The LY411575 γ-secretase inhibitor (Pan-NOTCH inhibitor) was used to block NOTCH signaling in MDA-MB 231 cells. Results: Metastasis Initiating Cells (MICs) isolated from the lungs of nude mice carrying MCF-7RAF-1 xenografts exhibited a higher degree of genomic stability than primary tumor xenografts that was characterized by the absence of centrosome amplification and non-clonal chromosomal abnormalities. MICs also showed higher mammosphere forming capacity that was linked to lower expression of luminal marker CD24. Significantly, global transcriptome analysis showed that expression of NOTCH3 and HES1 stemness genes was increased in MICs. To corroborate the role of NOTCH signaling in inducing metastatic seeding, MDA-MB 231 breast cancer cells were pre-treated with 1 µM of LY411575 After 72 hours viable cells were injected into the tail vein of immune-compromised mice to develop lung metastases. While animals injected with untreated MDA-MB 231 cells developed lung metastases, those injected with the LY411575-treated MDA-MB 231 cells failed to develop lung metastatic lesions. Conclusions: These preliminary findings demonstrate the role of NOTCH stemness signaling in promoting metastatic seeding of breast cancer cells. Since NOTCH signaling is a “druggable target”, these results also provide the rationale to develop novel NOTCH-targeted therapies to inhibit tumor stemness and early onset of distant metastases. Citation Format: Alexey Leontovich, Jeffrey Salisbury, Candace L. Haddox, Lisa Mills, Tufia Haddad, James McCubrey, Matthew Goetz, James Ingle, Evanthia Galanis, Antonino B. D'Assoro. NOTCH signaling promotes metastatic seeding and growth of human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4851. doi:10.1158/1538-7445.AM2017-4851

Abstract 5274: Wnt inhibitory factor 1 reduces the growth and migration of human adenoid cystic carcinoma cells

Abstract Background: Adenoid cystic carcinoma (ACC) is a common malignancy that arises in major and minor salivary glands. It is well characterized by relatively high rate of local recurrence, and late onset of distant metastases, which cause high morbidity and mortality. Dysregulation in the Wingless-type (Wnt)/β-catenin pathway contributes to many human tumors. Here, we report that downregulation of an important Wnt antagonist, Wnt inhibitory factor 1 (WIF1), promotes ACC cell proliferation and migration. Aims: To determine the status of WIF1 and study the effects of WIF1 on human adenoid cystic carcinoma cell growth, migration, spheroid formation and senescence. Methods: Genomic DNA isolated from human adenoid cystic carcinoma cell lines (ACC52 and ACC112) was used for methylation-specific PCR after bisulfite modification. ACC52 and ACC112 cells were treated with a demethylating agent, 5-aza-2′-deoxycytidine (DAC) [50 µM for 4 days], and used for total RNA isolation and real-time RT-PCR to determine WIF1 mRNA expression. To determine the growth suppressive effects of WIF1, ACC52 and ACC112 cells were transiently transfected with either pCI blast (vector) or pCI blast-WIF1 and assessed for cell proliferation, migration, spheroid formation and senescence. Cell proliferation was determined at different time intervals (24, 48, 72 h) by hexosaminidase assay. Cell migration and spheroid formation were assessed by scratch assay and soft agar assay, respectively. Cellular senescence was determined using senescence β-galactosidase staining kit. Results: Methylation-specific PCR demonstrate that WIF1 is silenced by promoter methylation in ACC cells. DAC treatment increased the WIF1 mRNA expression by 2.3-fold and 3.8-fold in ACC52 and ACC112 cells, respectively compared with vehicle treatment. WIF1 significantly decreased the proliferation and migration of adenoid cystic carcinoma cells. Additionally, WIF1 significantly decreased the number of spheroids formed at 7 and 17 days. Furthermore, WIF1 induced a remarkable increase in cellular senescence in both the cell lines. Conclusions: We demonstrate that WIF1 is downregulated by promoter hypermethylation in human adenoid cystic carcinoma cells. Importantly, WIF1 inhibited the cell growth, migration and cancer stemness, while inducing cellular senescence. Our findings suggest that WIF1 is a potent growth inhibitor of adenoid cystic carcinoma cells and therefore could be a potential therapeutic agent for ACC. Grant support: This work was supported by the Adenoid Cystic Carcinoma Research Foundation (LQ). LQ holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology. Citation Format: Ilangovan Ramachandran, Vengatesh Ganapathy, Lurdes Queimado. Wnt inhibitory factor 1 reduces the growth and migration of human adenoid cystic carcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5274. doi:10.1158/1538-7445.AM2014-5274

What type of patients with lesions of the pancreas and spine are suitable candidates for treatment with the CyberKnife robotic radiosurgical system?

AbstractMaterials & methodsA systematic literature review was conducted to critically examine patient selection for patients undergoing stereotactic body radiotherapy (SBRT) to the spine and pancreas on the CyberKnife robotic radiosurgical system (CK). Online databases were searched and data was collected and ranked using a system from the Scottish Intercollegiate Guideline Network. The quality of the evidence analysed was insufficient to generate universal recommendations. However, the conclusions reached do help to demonstrate the safety and efficacy of CK treatment to both pancreatic and spinal patients.ResultsExcellent local control rates and minimal acute toxicity were reported within the spinal literature with uncertainties remaining with regard to the precise tolerance of the spinal cord and the reliability of current toxicity prediction methods. For pancreatic patients prognosis remains dismal due to the tendency for patients to present with advanced or inoperable disease. Combinations of CK SBRT and Gemcitabine chemotherapy are given though regimes vary and overall survival is not extended due to the rapid onset of distant metastases. New chemotherapy agents are required as well as better means of predicting response to treatment.ConclusionNo randomised controlled trials or meta-analyses were identified in the review and these are required in order to generate universal guidelines

Age as a key factor influencing metastasizing patterns and disease‐specific survival after sentinel lymph node biopsy for cutaneous melanoma

In our study, we investigated the impact of the constitutional factor age on the clinical courses of melanoma patients with sentinel lymph node (SLN) biopsy. Descriptive statistics, Kaplan-Meier estimates, logistic regression analysis and the Cox proportional hazards model were used to study a population of 2,268 consecutive patients from three German melanoma centers. Younger age was significantly related to less advanced primary tumors. Nevertheless, patients younger than 40 years of age had a twofold risk of being SLN-positive (p < 0.000001). Of the young patients with primary melanomas with a thickness of 0.76 mm to 1.0 mm, 19.7% were SLN-positive. Using multivariate analysis, younger age, increasing Breslow thickness, ulceration and male sex were significantly related to a higher probability of SLN-metastasis. During follow-up, older patients displayed a significantly increased risk of in-transit recurrences (p = 0.000002) and lymph node recurrences (p = 0.0004). With respect to melanoma specific overall survival the patient's age was highly significant in the multivariate analysis. The unfavorable effect of being older was significant in the subgroups with positive and negative SLNs. Age remained also significant for the survival after the onset of distant metastases (p = 0.002). In conclusion, the patient's age is a strong and independent predictor of melanoma-specific survival in patients with localized melanomas, in patients with positive SLNs and after the onset of distant metastases. Younger patients have a better prognosis despite their higher probability of SLN metastasis. Older patients are less frequently SLN-positive but have a higher risk of loco-regional recurrence.

Prostate specific antigen doubling time (PSADT) predicts for distant failure and prostate cancer specific survival (PCSS) in men with biochemical relapse after radical prostatectomy (RP)

4555 Background: Patients (pts) with biochemical (PSA) relapse after RP represent a rapidly rising population in whom appropriate standards of care remain undefined. Over the past several years we have focused on studying the natural history of these pts. Our previous report (Pound et al; JAMA 1999) suggests that the Gleason score, time of PSA relapse (>0.2 ng/ml) and PSADT are the strongest predictors of the probability of distant metastasis (DM) (Cox model). A recent update (Partin; AUA 2003, Eisenberger; ASCO 2003) suggests that PSADT overrides the other parameters in the prediction of DM. Our experience has been expanded (> 1000 additional pts and longer follow-up). We evaluate the relationship between PSADT and PCSS. Methods: 4,415 pts underwent a RP from 1982–2003 and 825 demonstrated evidence of PSA relapse. All pts were followed with yearly PSAs with no androgen deprivation given until development of DM. Cox-proportional hazards and Kaplan-Meier survival analyses were completed with time from PSA relapse to censoring (last follow-up) or death used as endpoint. Results: 825/4,415 demonstrated PSA relapse (mean time 8.4yrs), 170/825(20.6%) developed DM and 109/825(13%) have died of prostate cancer (PCa). PSADT was calculated on 411 pts (mean 9 PSAs /pt, range 2–33), ROC-AUC for PSADT prediction of PCSS was 0.77. Conclusions: PSADT is a potent predictor of the probability of DM and PCSS. Pts with PSADT ≤10 mos. are at significant risk for developing DM and dying of PCa. In this group, clinical trials should evaluate progression-free and overall survival with aggressive approaches. Pts with PSADT of >10 mos. may be observed or treated to delay onset of DM. (Supported by CAPCURE). No significant financial relationships to disclose.

Malignant melanoma prognostic factors 6: distant metastases and length of survival.

Surgical resectability is the most important prognostic factor for determining the length of survival following distant metastases. Other important factors that derive prognostic significance from their correlation with surgical resectability include (1) number of metastatic sites, (2) performance status, (3) initial site of metastases, (4) interval between initial diagnosis of primary tumor and onset of distant metastases. Factors which have little or no prognostic value include location of the primary tumor, sex, age and histological characteristics of the primary tumor.